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Is the presence of enanthem a clue for COVID-19?
Larger studies should explore and confirm this association, the study’s authors and other experts suggested.
Dermatologists are already aware of the connection between enanthem and viral etiology. “As seen with other viral infections, we wondered if COVID-19 could produce enanthem in addition to skin rash exanthem,” one of the study author’s, Juan Jiménez-Cauhe, MD, a dermatologist with Hospital Universitario Ramon y Cajal, Madrid, said in an interview. He and his colleagues summarized their findings in a research letter in JAMA Dermatology.
They examined the oral cavity of 21 COVID-19 patients at a tertiary care hospital who also had a skin rash from March 30 to April 8. They classified enanthems into four categories: petechial, macular, macular with petechiae, or erythematovesicular. Six of the patients presented with oral lesions, all of them located in the palate; in one patient, the enanthem was macular, it was petechial in two patients and was macular with petechiae in three patients. The six patients ranged between the ages of 40 and 69 years; four were women.
Petechial or vesicular patterns are often associated with viral infections. In this particular study, the investigators did not observe vesicular lesions.
On average, mucocutaneous lesions appeared about 12 days after the onset of COVID-19 symptoms. “Interestingly, this latency was shorter in patients with petechial enanthem, compared with those with a macular lesion with petechiae appearance,” the authors wrote.
This shorter time might suggest an association for SARS-CoV-2, said Dr. Jiménez-Cauhe. Strong cough may have also caused petechial lesions on the palate, but it’s unlikely, as they appeared close in time to COVID-19 symptoms. It’s also unlikely that any drugs caused the lesions, as drug rashes can take 2-3 weeks to appear.
This fits in line with other evidence of broader skin manifestations appearing at the same time or after COVID-19, Esther Freeman, MD, said in an interview. Dr. Freeman, director of global health dermatology at Massachusetts General Hospital, Boston, is the principal investigator of the COVID-19 Dermatology Registry, a collaboration of the American Academy of Dermatology and International League of Dermatological Societies.
The study’s small cohort made it difficult to establish a solid association between the oral lesions and SARS-CoV-2. “However, the presence of enanthem in a patient with a skin rash is a useful finding that suggests a viral etiology rather than a drug reaction. This is particularly useful in COVID-19 patients, who were receiving many drugs as part of the treatment,” Dr. Jimenez-Cauhe said. Future studies should assess whether the presence of enanthem and exanthem lead physicians to consider SARS-CoV-2 as possible agents, ruling out infection with a blood or nasopharyngeal test.
This study adds to the growing body of knowledge on cutaneous and mucocutaneous findings associated with SARS-CoV-2 infection, Jules Lipoff, MD, of the department of dermatology, University of Pennsylvania, Philadelphia, said in an interview. “One challenge in evaluating these findings is that these findings are nonspecific, and medication reactions can often cause similar rashes, such as morbilliform eruptions that can be associated with both viruses and medications.”
Enanthems, as the study authors noted, are more specific to viral infections and are less commonly associated with medication reactions. “So, even though this is a small case series with significant limitations, it does add more evidence that COVID-19 is directly responsible for findings in the skin and mucous membranes,” said Dr. Lipoff.
Dr. Freeman noted that the study may also encourage clinicians to look in a patient’s mouth when assessing for SARS-CoV-2. Additional research should examine these data in a larger population.
Several studies by Dr. Freeman, Dr. Lipoff, and others strongly suggest that SARS-CoV-2 has a spectrum of associated dermatologic manifestations. One evaluated perniolike skin lesions (J Am Acad Dermatol. 2020 Aug; 83[2]:486-92). The other was a case series from the COVID-19 registry that examined 716 cases of new-onset dermatologic symptoms in patients from 31 countries with confirmed/suspected SARS-CoV-2 (J Am Acad Dermatol. 2020 Jul 2;S0190-9622[20]32126-5.).
The authors of the report had no disclosures.
SOURCE: Jimenez-Cauhe J et al. JAMA Dermatol. 2020 Jul 15. doi: 10.1001/jamadermatol.2020.2550.
Larger studies should explore and confirm this association, the study’s authors and other experts suggested.
Dermatologists are already aware of the connection between enanthem and viral etiology. “As seen with other viral infections, we wondered if COVID-19 could produce enanthem in addition to skin rash exanthem,” one of the study author’s, Juan Jiménez-Cauhe, MD, a dermatologist with Hospital Universitario Ramon y Cajal, Madrid, said in an interview. He and his colleagues summarized their findings in a research letter in JAMA Dermatology.
They examined the oral cavity of 21 COVID-19 patients at a tertiary care hospital who also had a skin rash from March 30 to April 8. They classified enanthems into four categories: petechial, macular, macular with petechiae, or erythematovesicular. Six of the patients presented with oral lesions, all of them located in the palate; in one patient, the enanthem was macular, it was petechial in two patients and was macular with petechiae in three patients. The six patients ranged between the ages of 40 and 69 years; four were women.
Petechial or vesicular patterns are often associated with viral infections. In this particular study, the investigators did not observe vesicular lesions.
On average, mucocutaneous lesions appeared about 12 days after the onset of COVID-19 symptoms. “Interestingly, this latency was shorter in patients with petechial enanthem, compared with those with a macular lesion with petechiae appearance,” the authors wrote.
This shorter time might suggest an association for SARS-CoV-2, said Dr. Jiménez-Cauhe. Strong cough may have also caused petechial lesions on the palate, but it’s unlikely, as they appeared close in time to COVID-19 symptoms. It’s also unlikely that any drugs caused the lesions, as drug rashes can take 2-3 weeks to appear.
This fits in line with other evidence of broader skin manifestations appearing at the same time or after COVID-19, Esther Freeman, MD, said in an interview. Dr. Freeman, director of global health dermatology at Massachusetts General Hospital, Boston, is the principal investigator of the COVID-19 Dermatology Registry, a collaboration of the American Academy of Dermatology and International League of Dermatological Societies.
The study’s small cohort made it difficult to establish a solid association between the oral lesions and SARS-CoV-2. “However, the presence of enanthem in a patient with a skin rash is a useful finding that suggests a viral etiology rather than a drug reaction. This is particularly useful in COVID-19 patients, who were receiving many drugs as part of the treatment,” Dr. Jimenez-Cauhe said. Future studies should assess whether the presence of enanthem and exanthem lead physicians to consider SARS-CoV-2 as possible agents, ruling out infection with a blood or nasopharyngeal test.
This study adds to the growing body of knowledge on cutaneous and mucocutaneous findings associated with SARS-CoV-2 infection, Jules Lipoff, MD, of the department of dermatology, University of Pennsylvania, Philadelphia, said in an interview. “One challenge in evaluating these findings is that these findings are nonspecific, and medication reactions can often cause similar rashes, such as morbilliform eruptions that can be associated with both viruses and medications.”
Enanthems, as the study authors noted, are more specific to viral infections and are less commonly associated with medication reactions. “So, even though this is a small case series with significant limitations, it does add more evidence that COVID-19 is directly responsible for findings in the skin and mucous membranes,” said Dr. Lipoff.
Dr. Freeman noted that the study may also encourage clinicians to look in a patient’s mouth when assessing for SARS-CoV-2. Additional research should examine these data in a larger population.
Several studies by Dr. Freeman, Dr. Lipoff, and others strongly suggest that SARS-CoV-2 has a spectrum of associated dermatologic manifestations. One evaluated perniolike skin lesions (J Am Acad Dermatol. 2020 Aug; 83[2]:486-92). The other was a case series from the COVID-19 registry that examined 716 cases of new-onset dermatologic symptoms in patients from 31 countries with confirmed/suspected SARS-CoV-2 (J Am Acad Dermatol. 2020 Jul 2;S0190-9622[20]32126-5.).
The authors of the report had no disclosures.
SOURCE: Jimenez-Cauhe J et al. JAMA Dermatol. 2020 Jul 15. doi: 10.1001/jamadermatol.2020.2550.
Larger studies should explore and confirm this association, the study’s authors and other experts suggested.
Dermatologists are already aware of the connection between enanthem and viral etiology. “As seen with other viral infections, we wondered if COVID-19 could produce enanthem in addition to skin rash exanthem,” one of the study author’s, Juan Jiménez-Cauhe, MD, a dermatologist with Hospital Universitario Ramon y Cajal, Madrid, said in an interview. He and his colleagues summarized their findings in a research letter in JAMA Dermatology.
They examined the oral cavity of 21 COVID-19 patients at a tertiary care hospital who also had a skin rash from March 30 to April 8. They classified enanthems into four categories: petechial, macular, macular with petechiae, or erythematovesicular. Six of the patients presented with oral lesions, all of them located in the palate; in one patient, the enanthem was macular, it was petechial in two patients and was macular with petechiae in three patients. The six patients ranged between the ages of 40 and 69 years; four were women.
Petechial or vesicular patterns are often associated with viral infections. In this particular study, the investigators did not observe vesicular lesions.
On average, mucocutaneous lesions appeared about 12 days after the onset of COVID-19 symptoms. “Interestingly, this latency was shorter in patients with petechial enanthem, compared with those with a macular lesion with petechiae appearance,” the authors wrote.
This shorter time might suggest an association for SARS-CoV-2, said Dr. Jiménez-Cauhe. Strong cough may have also caused petechial lesions on the palate, but it’s unlikely, as they appeared close in time to COVID-19 symptoms. It’s also unlikely that any drugs caused the lesions, as drug rashes can take 2-3 weeks to appear.
This fits in line with other evidence of broader skin manifestations appearing at the same time or after COVID-19, Esther Freeman, MD, said in an interview. Dr. Freeman, director of global health dermatology at Massachusetts General Hospital, Boston, is the principal investigator of the COVID-19 Dermatology Registry, a collaboration of the American Academy of Dermatology and International League of Dermatological Societies.
The study’s small cohort made it difficult to establish a solid association between the oral lesions and SARS-CoV-2. “However, the presence of enanthem in a patient with a skin rash is a useful finding that suggests a viral etiology rather than a drug reaction. This is particularly useful in COVID-19 patients, who were receiving many drugs as part of the treatment,” Dr. Jimenez-Cauhe said. Future studies should assess whether the presence of enanthem and exanthem lead physicians to consider SARS-CoV-2 as possible agents, ruling out infection with a blood or nasopharyngeal test.
This study adds to the growing body of knowledge on cutaneous and mucocutaneous findings associated with SARS-CoV-2 infection, Jules Lipoff, MD, of the department of dermatology, University of Pennsylvania, Philadelphia, said in an interview. “One challenge in evaluating these findings is that these findings are nonspecific, and medication reactions can often cause similar rashes, such as morbilliform eruptions that can be associated with both viruses and medications.”
Enanthems, as the study authors noted, are more specific to viral infections and are less commonly associated with medication reactions. “So, even though this is a small case series with significant limitations, it does add more evidence that COVID-19 is directly responsible for findings in the skin and mucous membranes,” said Dr. Lipoff.
Dr. Freeman noted that the study may also encourage clinicians to look in a patient’s mouth when assessing for SARS-CoV-2. Additional research should examine these data in a larger population.
Several studies by Dr. Freeman, Dr. Lipoff, and others strongly suggest that SARS-CoV-2 has a spectrum of associated dermatologic manifestations. One evaluated perniolike skin lesions (J Am Acad Dermatol. 2020 Aug; 83[2]:486-92). The other was a case series from the COVID-19 registry that examined 716 cases of new-onset dermatologic symptoms in patients from 31 countries with confirmed/suspected SARS-CoV-2 (J Am Acad Dermatol. 2020 Jul 2;S0190-9622[20]32126-5.).
The authors of the report had no disclosures.
SOURCE: Jimenez-Cauhe J et al. JAMA Dermatol. 2020 Jul 15. doi: 10.1001/jamadermatol.2020.2550.
FROM JAMA DERMATOLOGY
Sewage as our salvation: Tracking COVID-19
“The sewer is the conscience of the city. Everything there converges and confronts everything else. In that livid spot there are shades, but there are no longer any secrets.” Victor Hugo – “Les Miserables”
To get a sense of the prevalence of COVID-19 in a community you need to test hundreds to thousands of people. This is difficult, resource intensive, and requires cooperation for testing among people both with and without symptoms.
In various locations from China to medieval London, there have been attempts to utilize human excrement for the betterment of mankind, from employing it as fertilizer to processing it to make gunpowder. Such attempts did not always work as planned. The use of sewage for fertilizer in Europe and the United States in the 1840s and 1850s led to the spread of waterborne diseases, including cholera and typhoid. As the importance of sanitary elimination of human waste became ever clearer, ideas and technology for our modern system of sewage management evolved. We have since advanced a great deal, so that all industrialized nations now have a well-developed system for clean water entry, as well as sewage treatment and disposal. Nonetheless, there remains a nagging question of whether human waste could be used for something productive.1
In the early 2000s, SCIM was developed as a technique to assess population-level human health and disease. In SCIM, untreated sewage is tested for a chemical of interest which reflects a health parameter for a community. Chemicals of interest and usage rates can be calculated for substances as varied as opioids, tobacco, pesticides, and even nonnutritive sweeteners. For instance, relative opioid use can be calculated over time for a given “sewershed” or sewage catchment area. The calculation of community-wide exposure to substances as a means of getting real-time data on shifts of usage without having to collect and collate data from thousands of individuals has been termed wastewater-based epidemiology.
We use urine and stool testing in so many other areas, such as urinalysis, urine drug testing, urine Legionella antigen testing, and stool testing for common pathogens. What a rich source of information is present in the combination of urine and stool that collectively make up sewage! With the average volume of urine per adult being approximately 1 liter daily (and with urine calculated to be approximately 1% of wastewater), accurate analytic techniques can estimate per capita exposure to different substances. Applications of wastewater-based epidemiology have included tracking community prevalence of enteric viral infections, opioid and tobacco use, and many other indicators of health and disease.2
Given the enormous work in the field over the last 2 decades and that SARS-CoV-2 RNA has been detected in feces of both symptomatic and asymptomatic patients, it was only a short conceptual step for those familiar with sewage epidemiology to consider adapting it to assess the prevalence of COVID-19 in a community.
An elegant study collected untreated sewage from southeast Queensland, Australia. The sewage was processed, concentrated, and then tested with reverse transcriptase polymerase chain reaction analysis for SARS-CoV-2 RNA. The number of RNA copies was then entered into an equation that included the population served by the sewage encatchment area, as well as the measured liters of wastewater and grams of feces per day. This provided an estimate of the number of persons infected in the community, and the researchers were able to show reasonable agreement between the numbers estimated by sewage analysis and that found in traditional clinical testing.3,4
The promise of wastewater-based epidemiology is large. Early research indicates that quantification of viral particles in sewage can be accurately assessed and correlated with the prevalence of the infection in the community. Such levels can then be used to track infection rates of COVID-19 over time, as well as to compare the relative rates in different communities.
Our sewage may hold the answer to accurately and easily tracking COVID-19, and ultimately help us gain a better hold on this disease.
Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. They have no conflicts related to the content of this piece.
References
1. History of water supply and sanitation. Wikipedia, https://en.wikipedia.org/wiki/History_of_water_supply_and_sanitation.
2. Daughton C. Monitoring wastewater for assessing community health: Sewage Chemical-Information Mining (SCIM). Sci Total Environ. 2017 Nov 29. doi: 10.1016/j.scitotenv.2017.11.102.
3. Ahmed W et al. First confirmed detection of SARS-CoV-2 in untreated wastewater in Australia: A proof of concept for the wastewater surveillance of COVID-19 in the community. Sci Total Environ. 2020 Apr 18. doi: doi.org/10.1016/j.scitotenv.2020.138764.
4. Daughton C. The international imperative to rapidly and inexpensively monitor community-wide COVID-19 infection status and trends. Sci Total Environ. 2020 Mar 23. doi: 10.1016/j.scitotenv.2020.138149.
“The sewer is the conscience of the city. Everything there converges and confronts everything else. In that livid spot there are shades, but there are no longer any secrets.” Victor Hugo – “Les Miserables”
To get a sense of the prevalence of COVID-19 in a community you need to test hundreds to thousands of people. This is difficult, resource intensive, and requires cooperation for testing among people both with and without symptoms.
In various locations from China to medieval London, there have been attempts to utilize human excrement for the betterment of mankind, from employing it as fertilizer to processing it to make gunpowder. Such attempts did not always work as planned. The use of sewage for fertilizer in Europe and the United States in the 1840s and 1850s led to the spread of waterborne diseases, including cholera and typhoid. As the importance of sanitary elimination of human waste became ever clearer, ideas and technology for our modern system of sewage management evolved. We have since advanced a great deal, so that all industrialized nations now have a well-developed system for clean water entry, as well as sewage treatment and disposal. Nonetheless, there remains a nagging question of whether human waste could be used for something productive.1
In the early 2000s, SCIM was developed as a technique to assess population-level human health and disease. In SCIM, untreated sewage is tested for a chemical of interest which reflects a health parameter for a community. Chemicals of interest and usage rates can be calculated for substances as varied as opioids, tobacco, pesticides, and even nonnutritive sweeteners. For instance, relative opioid use can be calculated over time for a given “sewershed” or sewage catchment area. The calculation of community-wide exposure to substances as a means of getting real-time data on shifts of usage without having to collect and collate data from thousands of individuals has been termed wastewater-based epidemiology.
We use urine and stool testing in so many other areas, such as urinalysis, urine drug testing, urine Legionella antigen testing, and stool testing for common pathogens. What a rich source of information is present in the combination of urine and stool that collectively make up sewage! With the average volume of urine per adult being approximately 1 liter daily (and with urine calculated to be approximately 1% of wastewater), accurate analytic techniques can estimate per capita exposure to different substances. Applications of wastewater-based epidemiology have included tracking community prevalence of enteric viral infections, opioid and tobacco use, and many other indicators of health and disease.2
Given the enormous work in the field over the last 2 decades and that SARS-CoV-2 RNA has been detected in feces of both symptomatic and asymptomatic patients, it was only a short conceptual step for those familiar with sewage epidemiology to consider adapting it to assess the prevalence of COVID-19 in a community.
An elegant study collected untreated sewage from southeast Queensland, Australia. The sewage was processed, concentrated, and then tested with reverse transcriptase polymerase chain reaction analysis for SARS-CoV-2 RNA. The number of RNA copies was then entered into an equation that included the population served by the sewage encatchment area, as well as the measured liters of wastewater and grams of feces per day. This provided an estimate of the number of persons infected in the community, and the researchers were able to show reasonable agreement between the numbers estimated by sewage analysis and that found in traditional clinical testing.3,4
The promise of wastewater-based epidemiology is large. Early research indicates that quantification of viral particles in sewage can be accurately assessed and correlated with the prevalence of the infection in the community. Such levels can then be used to track infection rates of COVID-19 over time, as well as to compare the relative rates in different communities.
Our sewage may hold the answer to accurately and easily tracking COVID-19, and ultimately help us gain a better hold on this disease.
Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. They have no conflicts related to the content of this piece.
References
1. History of water supply and sanitation. Wikipedia, https://en.wikipedia.org/wiki/History_of_water_supply_and_sanitation.
2. Daughton C. Monitoring wastewater for assessing community health: Sewage Chemical-Information Mining (SCIM). Sci Total Environ. 2017 Nov 29. doi: 10.1016/j.scitotenv.2017.11.102.
3. Ahmed W et al. First confirmed detection of SARS-CoV-2 in untreated wastewater in Australia: A proof of concept for the wastewater surveillance of COVID-19 in the community. Sci Total Environ. 2020 Apr 18. doi: doi.org/10.1016/j.scitotenv.2020.138764.
4. Daughton C. The international imperative to rapidly and inexpensively monitor community-wide COVID-19 infection status and trends. Sci Total Environ. 2020 Mar 23. doi: 10.1016/j.scitotenv.2020.138149.
“The sewer is the conscience of the city. Everything there converges and confronts everything else. In that livid spot there are shades, but there are no longer any secrets.” Victor Hugo – “Les Miserables”
To get a sense of the prevalence of COVID-19 in a community you need to test hundreds to thousands of people. This is difficult, resource intensive, and requires cooperation for testing among people both with and without symptoms.
In various locations from China to medieval London, there have been attempts to utilize human excrement for the betterment of mankind, from employing it as fertilizer to processing it to make gunpowder. Such attempts did not always work as planned. The use of sewage for fertilizer in Europe and the United States in the 1840s and 1850s led to the spread of waterborne diseases, including cholera and typhoid. As the importance of sanitary elimination of human waste became ever clearer, ideas and technology for our modern system of sewage management evolved. We have since advanced a great deal, so that all industrialized nations now have a well-developed system for clean water entry, as well as sewage treatment and disposal. Nonetheless, there remains a nagging question of whether human waste could be used for something productive.1
In the early 2000s, SCIM was developed as a technique to assess population-level human health and disease. In SCIM, untreated sewage is tested for a chemical of interest which reflects a health parameter for a community. Chemicals of interest and usage rates can be calculated for substances as varied as opioids, tobacco, pesticides, and even nonnutritive sweeteners. For instance, relative opioid use can be calculated over time for a given “sewershed” or sewage catchment area. The calculation of community-wide exposure to substances as a means of getting real-time data on shifts of usage without having to collect and collate data from thousands of individuals has been termed wastewater-based epidemiology.
We use urine and stool testing in so many other areas, such as urinalysis, urine drug testing, urine Legionella antigen testing, and stool testing for common pathogens. What a rich source of information is present in the combination of urine and stool that collectively make up sewage! With the average volume of urine per adult being approximately 1 liter daily (and with urine calculated to be approximately 1% of wastewater), accurate analytic techniques can estimate per capita exposure to different substances. Applications of wastewater-based epidemiology have included tracking community prevalence of enteric viral infections, opioid and tobacco use, and many other indicators of health and disease.2
Given the enormous work in the field over the last 2 decades and that SARS-CoV-2 RNA has been detected in feces of both symptomatic and asymptomatic patients, it was only a short conceptual step for those familiar with sewage epidemiology to consider adapting it to assess the prevalence of COVID-19 in a community.
An elegant study collected untreated sewage from southeast Queensland, Australia. The sewage was processed, concentrated, and then tested with reverse transcriptase polymerase chain reaction analysis for SARS-CoV-2 RNA. The number of RNA copies was then entered into an equation that included the population served by the sewage encatchment area, as well as the measured liters of wastewater and grams of feces per day. This provided an estimate of the number of persons infected in the community, and the researchers were able to show reasonable agreement between the numbers estimated by sewage analysis and that found in traditional clinical testing.3,4
The promise of wastewater-based epidemiology is large. Early research indicates that quantification of viral particles in sewage can be accurately assessed and correlated with the prevalence of the infection in the community. Such levels can then be used to track infection rates of COVID-19 over time, as well as to compare the relative rates in different communities.
Our sewage may hold the answer to accurately and easily tracking COVID-19, and ultimately help us gain a better hold on this disease.
Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. They have no conflicts related to the content of this piece.
References
1. History of water supply and sanitation. Wikipedia, https://en.wikipedia.org/wiki/History_of_water_supply_and_sanitation.
2. Daughton C. Monitoring wastewater for assessing community health: Sewage Chemical-Information Mining (SCIM). Sci Total Environ. 2017 Nov 29. doi: 10.1016/j.scitotenv.2017.11.102.
3. Ahmed W et al. First confirmed detection of SARS-CoV-2 in untreated wastewater in Australia: A proof of concept for the wastewater surveillance of COVID-19 in the community. Sci Total Environ. 2020 Apr 18. doi: doi.org/10.1016/j.scitotenv.2020.138764.
4. Daughton C. The international imperative to rapidly and inexpensively monitor community-wide COVID-19 infection status and trends. Sci Total Environ. 2020 Mar 23. doi: 10.1016/j.scitotenv.2020.138149.
Managing amidst COVID-19 (and everything else that ails us)
This year, medical media has been dominated by reporting on the devastating COVID-19 pandemic. Many studies and analyses have shown that staying at home, social distancing, quarantining of close contacts, and wearing face masks and face shields are effective ways of preventing spread.
Although initially there were no known effective treatments for severe COVID-19 infection (other than oxygen and ventilator support), we now know that dexamethasone,1 remdesivir,2 and convalescent plasma3 are effective in lessening the severity of illness and perhaps preventing death. That said, we will continue to struggle with COVID-19 for the foreseeable future.
But other medical illnesses actually predominate in terms of morbidity and mortality, even during this pandemic. For example, although there has been an average of roughly 5600 COVID-19-related deaths per week for the past 4 months,4 there are, on average, more than 54,000 deaths per week in the United States from other causes.5 This means that we must continue to tend to the other health care needs of our patients even as we deal with COVID-19.
In that light, JFP continues to publish practical, evidence-based clinical reviews designed to keep family physicians and other primary health care clinicians up to date on a variety of topics. For instance, in this issue of JFP, we have articles on:
- Opioid prescribing. Although opioids have risks, they remain potent medications for relief from acute pain, as well as cancer-related pain and chronic pain not sufficiently treated with other medications. Mahvan et al provide expert advice on maximizing benefit and minimizing the risks of opioid prescribing.
- Secondary ischemic stroke prevention. For patients who have suffered a transient ischemic attack or minor stroke, a mainstay of prevention is antiplatelet therapy. Aspirin alone used to be the treatment of choice, but research has demonstrated the value of adding another antiplatelet agent. Helmer et al’s thorough review reminds us that the antiplatelet drug of choice, in addition to aspirin, is clopidogrel, which should be used only for the first 30 days after the event because of an increased bleeding risk.
- Combatting Clostridioides difficile infection. CDI has been a difficult condition to treat, especially in high-risk patients. Zukauckas et al provide a comprehensive review of diagnosis and management. Vancomycin is now the drug of choice, and fecal transplant is highly effective in preventing recurrent CDI.
This diverse range of timely, practical, evidence-based guidance—in addition to coverage of COVID-19 and other rapidly emerging medical news stories—can all be found on our Web site at www.mdedge.com/familymedicine. We remain committed to supplying you with all of the information you need to provide your patients with the very best care—no matter what brings them in to see you.
1. Low-cost dexamethasone reduces death by up to one third in hospitalized patients with severe respiratory complications of COVID-19. Recovery: Randomised Evaluation of COVID-19 Therapy Web site. June 16, 2020. www.recoverytrial.net/news/low-cost-dexamethasone-reduces-death-by-up-to-one-third-in-hospitalised-patients-with-severe-respiratory-complications-of-covid-19. Accessed July 1, 2020.
2. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19—preliminary report [published online ahead of print]. N Engl J Med. doi: 10.1056/NEJMoa2007764.
3. Li L, Zhang W, Hu Y, et. al. Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial [published online ahead of print]. JAMA. doi:10.1001/jama.2020.10044.
4. Stokes EK, Zambrano LD, Anderson KN, et al. Coronavirus disease 2019 case surveillance—United States, January 22–May 30, 2020. MMWR Morb Mortal Wkly Rep. 2020;69:759-765.
5. Xu J, Murphy SL, Kochanek KD, et al. Mortality in the United States, 2018. NCHS Data Brief. 2020;1-8.
Editor-in-Chief
Editor-in-Chief
Editor-in-Chief
This year, medical media has been dominated by reporting on the devastating COVID-19 pandemic. Many studies and analyses have shown that staying at home, social distancing, quarantining of close contacts, and wearing face masks and face shields are effective ways of preventing spread.
Although initially there were no known effective treatments for severe COVID-19 infection (other than oxygen and ventilator support), we now know that dexamethasone,1 remdesivir,2 and convalescent plasma3 are effective in lessening the severity of illness and perhaps preventing death. That said, we will continue to struggle with COVID-19 for the foreseeable future.
But other medical illnesses actually predominate in terms of morbidity and mortality, even during this pandemic. For example, although there has been an average of roughly 5600 COVID-19-related deaths per week for the past 4 months,4 there are, on average, more than 54,000 deaths per week in the United States from other causes.5 This means that we must continue to tend to the other health care needs of our patients even as we deal with COVID-19.
In that light, JFP continues to publish practical, evidence-based clinical reviews designed to keep family physicians and other primary health care clinicians up to date on a variety of topics. For instance, in this issue of JFP, we have articles on:
- Opioid prescribing. Although opioids have risks, they remain potent medications for relief from acute pain, as well as cancer-related pain and chronic pain not sufficiently treated with other medications. Mahvan et al provide expert advice on maximizing benefit and minimizing the risks of opioid prescribing.
- Secondary ischemic stroke prevention. For patients who have suffered a transient ischemic attack or minor stroke, a mainstay of prevention is antiplatelet therapy. Aspirin alone used to be the treatment of choice, but research has demonstrated the value of adding another antiplatelet agent. Helmer et al’s thorough review reminds us that the antiplatelet drug of choice, in addition to aspirin, is clopidogrel, which should be used only for the first 30 days after the event because of an increased bleeding risk.
- Combatting Clostridioides difficile infection. CDI has been a difficult condition to treat, especially in high-risk patients. Zukauckas et al provide a comprehensive review of diagnosis and management. Vancomycin is now the drug of choice, and fecal transplant is highly effective in preventing recurrent CDI.
This diverse range of timely, practical, evidence-based guidance—in addition to coverage of COVID-19 and other rapidly emerging medical news stories—can all be found on our Web site at www.mdedge.com/familymedicine. We remain committed to supplying you with all of the information you need to provide your patients with the very best care—no matter what brings them in to see you.
This year, medical media has been dominated by reporting on the devastating COVID-19 pandemic. Many studies and analyses have shown that staying at home, social distancing, quarantining of close contacts, and wearing face masks and face shields are effective ways of preventing spread.
Although initially there were no known effective treatments for severe COVID-19 infection (other than oxygen and ventilator support), we now know that dexamethasone,1 remdesivir,2 and convalescent plasma3 are effective in lessening the severity of illness and perhaps preventing death. That said, we will continue to struggle with COVID-19 for the foreseeable future.
But other medical illnesses actually predominate in terms of morbidity and mortality, even during this pandemic. For example, although there has been an average of roughly 5600 COVID-19-related deaths per week for the past 4 months,4 there are, on average, more than 54,000 deaths per week in the United States from other causes.5 This means that we must continue to tend to the other health care needs of our patients even as we deal with COVID-19.
In that light, JFP continues to publish practical, evidence-based clinical reviews designed to keep family physicians and other primary health care clinicians up to date on a variety of topics. For instance, in this issue of JFP, we have articles on:
- Opioid prescribing. Although opioids have risks, they remain potent medications for relief from acute pain, as well as cancer-related pain and chronic pain not sufficiently treated with other medications. Mahvan et al provide expert advice on maximizing benefit and minimizing the risks of opioid prescribing.
- Secondary ischemic stroke prevention. For patients who have suffered a transient ischemic attack or minor stroke, a mainstay of prevention is antiplatelet therapy. Aspirin alone used to be the treatment of choice, but research has demonstrated the value of adding another antiplatelet agent. Helmer et al’s thorough review reminds us that the antiplatelet drug of choice, in addition to aspirin, is clopidogrel, which should be used only for the first 30 days after the event because of an increased bleeding risk.
- Combatting Clostridioides difficile infection. CDI has been a difficult condition to treat, especially in high-risk patients. Zukauckas et al provide a comprehensive review of diagnosis and management. Vancomycin is now the drug of choice, and fecal transplant is highly effective in preventing recurrent CDI.
This diverse range of timely, practical, evidence-based guidance—in addition to coverage of COVID-19 and other rapidly emerging medical news stories—can all be found on our Web site at www.mdedge.com/familymedicine. We remain committed to supplying you with all of the information you need to provide your patients with the very best care—no matter what brings them in to see you.
1. Low-cost dexamethasone reduces death by up to one third in hospitalized patients with severe respiratory complications of COVID-19. Recovery: Randomised Evaluation of COVID-19 Therapy Web site. June 16, 2020. www.recoverytrial.net/news/low-cost-dexamethasone-reduces-death-by-up-to-one-third-in-hospitalised-patients-with-severe-respiratory-complications-of-covid-19. Accessed July 1, 2020.
2. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19—preliminary report [published online ahead of print]. N Engl J Med. doi: 10.1056/NEJMoa2007764.
3. Li L, Zhang W, Hu Y, et. al. Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial [published online ahead of print]. JAMA. doi:10.1001/jama.2020.10044.
4. Stokes EK, Zambrano LD, Anderson KN, et al. Coronavirus disease 2019 case surveillance—United States, January 22–May 30, 2020. MMWR Morb Mortal Wkly Rep. 2020;69:759-765.
5. Xu J, Murphy SL, Kochanek KD, et al. Mortality in the United States, 2018. NCHS Data Brief. 2020;1-8.
1. Low-cost dexamethasone reduces death by up to one third in hospitalized patients with severe respiratory complications of COVID-19. Recovery: Randomised Evaluation of COVID-19 Therapy Web site. June 16, 2020. www.recoverytrial.net/news/low-cost-dexamethasone-reduces-death-by-up-to-one-third-in-hospitalised-patients-with-severe-respiratory-complications-of-covid-19. Accessed July 1, 2020.
2. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19—preliminary report [published online ahead of print]. N Engl J Med. doi: 10.1056/NEJMoa2007764.
3. Li L, Zhang W, Hu Y, et. al. Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial [published online ahead of print]. JAMA. doi:10.1001/jama.2020.10044.
4. Stokes EK, Zambrano LD, Anderson KN, et al. Coronavirus disease 2019 case surveillance—United States, January 22–May 30, 2020. MMWR Morb Mortal Wkly Rep. 2020;69:759-765.
5. Xu J, Murphy SL, Kochanek KD, et al. Mortality in the United States, 2018. NCHS Data Brief. 2020;1-8.
Oxford coronavirus vaccine ‘triggers immune response’
The early stage results, published in The Lancet, found that the candidate vaccine, known as ChAdOx1 nCoV-19, provoked a T-cell response peaking 14 days after vaccination, and an antibody response within 28 days.
Andrew Pollard, chief investigator on the study, and professor of pediatric infection and immunity at Oxford University, described the results as “encouraging”. He told a briefing convened by the Science Media Centre on Monday that it was “a really important milestone on the path to the development of the vaccine”.
In the Commons, the Health Secretary, Matt Hancock, hailed the results for taking us “one step closer to finding a vaccine that can potentially save lives, all around the world”.
The trial, which has so far involved 1,077 healthy adults, caused minor side effects when compared with a control group given a meningitis vaccine. Fatigue and headache were the most commonly reported reactions.
However, there were no serious adverse events from the vaccine, the researchers said.
‘Still a long way to go’
Sarah Gilbert, lead researcher of the vaccine development program, and professor of vaccinology at Oxford, cautioned that there was still a long way to go before the team could confirm that the vaccine could protect against developing COVID-19.
“The difficulty that we have, and that all vaccine developers have in trying to make a vaccine against this particular virus, is that we don’t know how strong that immune response needs to be,” she said.
“So, we can’t say just by looking at immune responses whether this is going to protect people or not. And the only way we’re going to find out is by doing the large phase 3 trials and wait for people to be infected as part of that trial before we know if the vaccine can work.”
The authors noted some limitations to their findings. They said more research was needed to confirm their results in different groups of people – including older age groups, those with other health conditions, and in ethnically and geographically diverse populations.
A notable result of the trial was that participants given a second dose of the vaccine appeared to display a stronger immune response, a finding that had influenced plans to “look at two dose regimes as well as one dose regimes in the phase 3 trial”, Prof Adrian Hill, director of Oxford’s Jenner Institute, confirmed.
ChAdOx1 nCoV-19 is made from a weakened version of an adenovirus that causes infections in chimpanzees. The virus has been genetically modified so that it cannot grow in humans.
On Monday, the government announced that it had struck a deal with AstraZeneca for access to 100 million doses of the Oxford vaccine, in addition to millions of doses of other promising candidate vaccines.
Expert reaction to the findings
The Medical Research Council helped to fund the trial. Executive Chair Professor Fiona Watt commented: “It is truly remarkable how fast this vaccine has progressed, with our support, through early clinical trials, and it is very encouraging that it shows no safety concerns and evokes strong immune responses.
“There is a lot that we don’t yet know about immunity to the virus that causes COVID-19. However, it seems that both antibody and T cell immunity are important, and this vaccine triggers both responses. The much anticipated next milestone will be the results of the larger trials that are happening now to find out if the vaccine will protect people from the virus.”
Jonathan Ball, professor of molecular virology at the University of Nottingham, told the SMC: “The results of the Oxford chimp adenovirus vaccine candidate show that the vaccine is able to generate antibodies and T cells in humans and these persisted for several weeks. Whilst encouraging there is still a long way to go before we can herald the arrival of a successful coronavirus vaccine.
“It is unclear whether the levels of immunity can protect against infection – that’s what the larger ongoing phase III trials are designed to test. Nor do we know if this vaccine can protect those most vulnerable to severe COVID-19 disease.”
Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, commented: “For the vaccine to be really useful, we not only need the larger studies conducted where COVID-19 is still occurring at a high rate, but we need to be reasonably sure that the protection lasts for a considerable time.”
He said it was also vital that people older than 55 were included in later trials.
Richard Torbett, chief executive of the Association of the British Pharmaceutical Industry, said: “Developing a vaccine is an incredibly difficult challenge; the fact that there are multiple candidates in development is hopefully a sign that the hard work will ultimately pay off.
“But we must be patient. Proving that a vaccine is safe and effective is a long process and we could still be many months away.”
This article first appeared on Medscape.com.
The early stage results, published in The Lancet, found that the candidate vaccine, known as ChAdOx1 nCoV-19, provoked a T-cell response peaking 14 days after vaccination, and an antibody response within 28 days.
Andrew Pollard, chief investigator on the study, and professor of pediatric infection and immunity at Oxford University, described the results as “encouraging”. He told a briefing convened by the Science Media Centre on Monday that it was “a really important milestone on the path to the development of the vaccine”.
In the Commons, the Health Secretary, Matt Hancock, hailed the results for taking us “one step closer to finding a vaccine that can potentially save lives, all around the world”.
The trial, which has so far involved 1,077 healthy adults, caused minor side effects when compared with a control group given a meningitis vaccine. Fatigue and headache were the most commonly reported reactions.
However, there were no serious adverse events from the vaccine, the researchers said.
‘Still a long way to go’
Sarah Gilbert, lead researcher of the vaccine development program, and professor of vaccinology at Oxford, cautioned that there was still a long way to go before the team could confirm that the vaccine could protect against developing COVID-19.
“The difficulty that we have, and that all vaccine developers have in trying to make a vaccine against this particular virus, is that we don’t know how strong that immune response needs to be,” she said.
“So, we can’t say just by looking at immune responses whether this is going to protect people or not. And the only way we’re going to find out is by doing the large phase 3 trials and wait for people to be infected as part of that trial before we know if the vaccine can work.”
The authors noted some limitations to their findings. They said more research was needed to confirm their results in different groups of people – including older age groups, those with other health conditions, and in ethnically and geographically diverse populations.
A notable result of the trial was that participants given a second dose of the vaccine appeared to display a stronger immune response, a finding that had influenced plans to “look at two dose regimes as well as one dose regimes in the phase 3 trial”, Prof Adrian Hill, director of Oxford’s Jenner Institute, confirmed.
ChAdOx1 nCoV-19 is made from a weakened version of an adenovirus that causes infections in chimpanzees. The virus has been genetically modified so that it cannot grow in humans.
On Monday, the government announced that it had struck a deal with AstraZeneca for access to 100 million doses of the Oxford vaccine, in addition to millions of doses of other promising candidate vaccines.
Expert reaction to the findings
The Medical Research Council helped to fund the trial. Executive Chair Professor Fiona Watt commented: “It is truly remarkable how fast this vaccine has progressed, with our support, through early clinical trials, and it is very encouraging that it shows no safety concerns and evokes strong immune responses.
“There is a lot that we don’t yet know about immunity to the virus that causes COVID-19. However, it seems that both antibody and T cell immunity are important, and this vaccine triggers both responses. The much anticipated next milestone will be the results of the larger trials that are happening now to find out if the vaccine will protect people from the virus.”
Jonathan Ball, professor of molecular virology at the University of Nottingham, told the SMC: “The results of the Oxford chimp adenovirus vaccine candidate show that the vaccine is able to generate antibodies and T cells in humans and these persisted for several weeks. Whilst encouraging there is still a long way to go before we can herald the arrival of a successful coronavirus vaccine.
“It is unclear whether the levels of immunity can protect against infection – that’s what the larger ongoing phase III trials are designed to test. Nor do we know if this vaccine can protect those most vulnerable to severe COVID-19 disease.”
Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, commented: “For the vaccine to be really useful, we not only need the larger studies conducted where COVID-19 is still occurring at a high rate, but we need to be reasonably sure that the protection lasts for a considerable time.”
He said it was also vital that people older than 55 were included in later trials.
Richard Torbett, chief executive of the Association of the British Pharmaceutical Industry, said: “Developing a vaccine is an incredibly difficult challenge; the fact that there are multiple candidates in development is hopefully a sign that the hard work will ultimately pay off.
“But we must be patient. Proving that a vaccine is safe and effective is a long process and we could still be many months away.”
This article first appeared on Medscape.com.
The early stage results, published in The Lancet, found that the candidate vaccine, known as ChAdOx1 nCoV-19, provoked a T-cell response peaking 14 days after vaccination, and an antibody response within 28 days.
Andrew Pollard, chief investigator on the study, and professor of pediatric infection and immunity at Oxford University, described the results as “encouraging”. He told a briefing convened by the Science Media Centre on Monday that it was “a really important milestone on the path to the development of the vaccine”.
In the Commons, the Health Secretary, Matt Hancock, hailed the results for taking us “one step closer to finding a vaccine that can potentially save lives, all around the world”.
The trial, which has so far involved 1,077 healthy adults, caused minor side effects when compared with a control group given a meningitis vaccine. Fatigue and headache were the most commonly reported reactions.
However, there were no serious adverse events from the vaccine, the researchers said.
‘Still a long way to go’
Sarah Gilbert, lead researcher of the vaccine development program, and professor of vaccinology at Oxford, cautioned that there was still a long way to go before the team could confirm that the vaccine could protect against developing COVID-19.
“The difficulty that we have, and that all vaccine developers have in trying to make a vaccine against this particular virus, is that we don’t know how strong that immune response needs to be,” she said.
“So, we can’t say just by looking at immune responses whether this is going to protect people or not. And the only way we’re going to find out is by doing the large phase 3 trials and wait for people to be infected as part of that trial before we know if the vaccine can work.”
The authors noted some limitations to their findings. They said more research was needed to confirm their results in different groups of people – including older age groups, those with other health conditions, and in ethnically and geographically diverse populations.
A notable result of the trial was that participants given a second dose of the vaccine appeared to display a stronger immune response, a finding that had influenced plans to “look at two dose regimes as well as one dose regimes in the phase 3 trial”, Prof Adrian Hill, director of Oxford’s Jenner Institute, confirmed.
ChAdOx1 nCoV-19 is made from a weakened version of an adenovirus that causes infections in chimpanzees. The virus has been genetically modified so that it cannot grow in humans.
On Monday, the government announced that it had struck a deal with AstraZeneca for access to 100 million doses of the Oxford vaccine, in addition to millions of doses of other promising candidate vaccines.
Expert reaction to the findings
The Medical Research Council helped to fund the trial. Executive Chair Professor Fiona Watt commented: “It is truly remarkable how fast this vaccine has progressed, with our support, through early clinical trials, and it is very encouraging that it shows no safety concerns and evokes strong immune responses.
“There is a lot that we don’t yet know about immunity to the virus that causes COVID-19. However, it seems that both antibody and T cell immunity are important, and this vaccine triggers both responses. The much anticipated next milestone will be the results of the larger trials that are happening now to find out if the vaccine will protect people from the virus.”
Jonathan Ball, professor of molecular virology at the University of Nottingham, told the SMC: “The results of the Oxford chimp adenovirus vaccine candidate show that the vaccine is able to generate antibodies and T cells in humans and these persisted for several weeks. Whilst encouraging there is still a long way to go before we can herald the arrival of a successful coronavirus vaccine.
“It is unclear whether the levels of immunity can protect against infection – that’s what the larger ongoing phase III trials are designed to test. Nor do we know if this vaccine can protect those most vulnerable to severe COVID-19 disease.”
Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, commented: “For the vaccine to be really useful, we not only need the larger studies conducted where COVID-19 is still occurring at a high rate, but we need to be reasonably sure that the protection lasts for a considerable time.”
He said it was also vital that people older than 55 were included in later trials.
Richard Torbett, chief executive of the Association of the British Pharmaceutical Industry, said: “Developing a vaccine is an incredibly difficult challenge; the fact that there are multiple candidates in development is hopefully a sign that the hard work will ultimately pay off.
“But we must be patient. Proving that a vaccine is safe and effective is a long process and we could still be many months away.”
This article first appeared on Medscape.com.
COVID vaccine tested in people shows early promise
the company says in a news release.
Researchers also reported some side effects in the 45 people in the phase I study, but no significant safety issues, the news release says.
The vaccine is among hundreds being tested worldwide in an effort to halt the pandemic that has killed nearly 600,000 worldwide.
A researcher testing the vaccine called the results encouraging but cautioned more study is needed. “Importantly, the vaccine resulted in a robust immune response,” Evan Anderson, MD, principal investigator for the trial at Emory University, says in a news release. Emory and Kaiser Permanente Washington Health Research Institute were the two sites for the study.
The company is already testing the vaccine in a larger group of people, known as a phase II trial. It plans to begin phase III trials in late July. Phase III trials involve testing the vaccine on an even larger group and are the final step before FDA approval.
The study results are published in The New England Journal of Medicine. The study was led by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
Moderna’s vaccine uses messenger RNA, also called mRNA. It carries the instruction for making the spike protein, a key protein on the surface of the virus that allows it to enter cells when a person is infected. After it’s injected, it goes to the immune cells and instructs them to make copies of the spike protein, acting as if the cells have been infected with the actual coronavirus. This allows other immune cells to develop immunity.
In the study, participants were divided into three groups of 15 people each. All groups received two vaccinations 28 days apart. Each group received a different strength of the vaccine – either 25, 100, or 250 micrograms.
Every person in the study developed antibodies that can block the infection. Most commonly reported side effects after the second vaccination in the 100-microgram group were fatigue, chills, headache, and muscle pains, ranging from mild to moderately severe.
The phase II study has 300 heathy adults ages 18-55, along with another 300 ages 55 and older
Moderna says it hopes to include about 30,000 participants at the 100-microgram dose level in the U.S. for the phase III trial. The estimated start date is July 27.
This article first appeared on WebMD.com.
the company says in a news release.
Researchers also reported some side effects in the 45 people in the phase I study, but no significant safety issues, the news release says.
The vaccine is among hundreds being tested worldwide in an effort to halt the pandemic that has killed nearly 600,000 worldwide.
A researcher testing the vaccine called the results encouraging but cautioned more study is needed. “Importantly, the vaccine resulted in a robust immune response,” Evan Anderson, MD, principal investigator for the trial at Emory University, says in a news release. Emory and Kaiser Permanente Washington Health Research Institute were the two sites for the study.
The company is already testing the vaccine in a larger group of people, known as a phase II trial. It plans to begin phase III trials in late July. Phase III trials involve testing the vaccine on an even larger group and are the final step before FDA approval.
The study results are published in The New England Journal of Medicine. The study was led by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
Moderna’s vaccine uses messenger RNA, also called mRNA. It carries the instruction for making the spike protein, a key protein on the surface of the virus that allows it to enter cells when a person is infected. After it’s injected, it goes to the immune cells and instructs them to make copies of the spike protein, acting as if the cells have been infected with the actual coronavirus. This allows other immune cells to develop immunity.
In the study, participants were divided into three groups of 15 people each. All groups received two vaccinations 28 days apart. Each group received a different strength of the vaccine – either 25, 100, or 250 micrograms.
Every person in the study developed antibodies that can block the infection. Most commonly reported side effects after the second vaccination in the 100-microgram group were fatigue, chills, headache, and muscle pains, ranging from mild to moderately severe.
The phase II study has 300 heathy adults ages 18-55, along with another 300 ages 55 and older
Moderna says it hopes to include about 30,000 participants at the 100-microgram dose level in the U.S. for the phase III trial. The estimated start date is July 27.
This article first appeared on WebMD.com.
the company says in a news release.
Researchers also reported some side effects in the 45 people in the phase I study, but no significant safety issues, the news release says.
The vaccine is among hundreds being tested worldwide in an effort to halt the pandemic that has killed nearly 600,000 worldwide.
A researcher testing the vaccine called the results encouraging but cautioned more study is needed. “Importantly, the vaccine resulted in a robust immune response,” Evan Anderson, MD, principal investigator for the trial at Emory University, says in a news release. Emory and Kaiser Permanente Washington Health Research Institute were the two sites for the study.
The company is already testing the vaccine in a larger group of people, known as a phase II trial. It plans to begin phase III trials in late July. Phase III trials involve testing the vaccine on an even larger group and are the final step before FDA approval.
The study results are published in The New England Journal of Medicine. The study was led by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
Moderna’s vaccine uses messenger RNA, also called mRNA. It carries the instruction for making the spike protein, a key protein on the surface of the virus that allows it to enter cells when a person is infected. After it’s injected, it goes to the immune cells and instructs them to make copies of the spike protein, acting as if the cells have been infected with the actual coronavirus. This allows other immune cells to develop immunity.
In the study, participants were divided into three groups of 15 people each. All groups received two vaccinations 28 days apart. Each group received a different strength of the vaccine – either 25, 100, or 250 micrograms.
Every person in the study developed antibodies that can block the infection. Most commonly reported side effects after the second vaccination in the 100-microgram group were fatigue, chills, headache, and muscle pains, ranging from mild to moderately severe.
The phase II study has 300 heathy adults ages 18-55, along with another 300 ages 55 and older
Moderna says it hopes to include about 30,000 participants at the 100-microgram dose level in the U.S. for the phase III trial. The estimated start date is July 27.
This article first appeared on WebMD.com.
It’s time to rethink your approach to C diff infection
CASE 1
Beth O, a 63-year-old woman, presents to the emergency department (ED) with a 2-week history of diarrhea (6 very loose, watery stools per day) and lower abdominal pain. The patient denies any vomiting, sick contacts, or recent travel. Past medical history includes varicose veins. Her only active medication is loperamide, as needed, for the past 2 weeks. Ms. O also recently completed a 10-day course of clindamycin for an infected laceration on her finger.
Ms. O’s laboratory values are unremarkable, with a normal white blood cell (WBC) count and serum creatinine (SCr) level. Abdominal computed tomography (CT) reveals some abnormal bowel dilatation and a slight increase in colon wall thickness. There is a high suspicion for Clostridioides difficile (formerly Clostridium difficile) infection (CDI), and stool sent for polymerase chain reaction (PCR) testing comes back positive for C difficile toxin B. It is revealed to be a strain other than the BI/NAP1/027 epidemic strain (which has a higher mortality rate).
How should this patient be treated?
CASE 2
Sixty-eight-year-old Barbara Z presents to the ED from her skilled nursing facility with persistent diarrhea and abdominal cramping. She was diagnosed with CDI about 2 months ago and reports that her symptoms resolved within 4 to 5 days after starting a 14-day course of oral metronidazole.
Her past medical history is notable for multiple myeloma with bone metastasis, for which she is actively undergoing chemotherapy treatment. She also has chronic kidney disease (baseline SCr, 2.2 mg/dL), hypertension, and anemia of chronic disease. The patient’s medications include amlodipine and cholecalciferol. Her chemotherapy regimen consists of bortezomib, lenalidomide, and dexamethasone. CT of the abdomen shows diffuse colon wall thickening with surrounding inflammatory stranding—concerning for pancolitis. There is no evidence of toxic megacolon or ileus.
Ms. Z’s laboratory values are notable for a WBC count of 15,900 cells/mL and an SCr of 4.1 mg/dL. She is started on oral levofloxacin and metronidazole due to concern for an intra-abdominal infection. PCR testing is positive for C difficile, and an enzyme immunoassay (EIA) for C difficile toxin is positive.
What factors put Ms. Z at risk for C difficile, and how should she be treated?
Continue to: C difficile is one of the most...
C difficile is one of the most commonly reported pathogens in health care–associated infections and affects almost 1% of all hospitalized patients in the United States each year.1 From 2001 to 2010, the incidence of CDI doubled in patients discharged from hospitals,2 with an estimated cost of more than $5 billion annually.3 Furthermore, rates of community-associated CDI continue to increase and account for about 40% of cases.4
After colonization in the intestine, C difficile releases 2 toxins (TcdA and TcdB) that cause colitis.5 Patients may present with mild diarrhea that can progress to abdominal pain, cramping, fever, and leukocytosis. Fulminant CDI can lead to the formation of pseudomembranes in the colon, toxic megacolon, bowel perforation, shock, and death.2
Beginning in the early 2000s, hospitals reported increases in severe cases of CDI.6 A specific strain known as BI/NAP1/027 was identified and characterized by fluoroquinolone resistance, increased spore formation, and a higher mortality rate.6
Further complicating matters … Recurrent CDI occurs in up to 10% to 30% of patients,7 typically within 14 to 45 days of completion of antibiotic pharmacotherapy for CDI.8 Recurrence is characterized by new-onset diarrhea or abdominal symptoms after completion of treatment for CDI.5
It typically begins with an antibiotic
Risk factors for CDI are listed in TABLE 1.9 The most important modifiable risk factor for initial and recurrent CDI is recent use of antibiotics.10 Most antibiotics can disrupt normal intestinal flora, causing colonization of C difficile, but the strongest association seems to be with third- and fourth-generation cephalosporins, fluoroquinolones, carbapenems, and clindamycin.11 The risk for CDI occurs during antibiotic treatment, as well as up to 3 months after completion of antibiotic therapy.7 Exposure to multiple antibiotics and extended duration of antibacterial therapy can greatly increase the risk for CDI, so antimicrobial stewardship is key.11
Continue to: Continuing antibiotics while attempting...
Continuing antibiotics while attempting to treat CDI reduces the patient’s clinical response to CDI treatment, which can lead to recurrence.12 The Infectious Diseases Society of America (IDSA) guidelines include a strong recommendation to discontinue concurrent antibiotics as soon as possible in these scenarios.11
Acid-suppression therapy has also been associated with CDI. The mechanism is thought to be an interruption in the protection provided by stomach acid, and use over time may reduce the diversity of flora within the gut microbiome.13 The data demonstrating an association between acid-suppression therapy and CDI is conflicting, which may be a result of confounding factors such as the severity of CDI illness and diarrhea induced by use of proton pump inhibitors (PPIs).4 IDSA guidelines do not provide a recommendation regarding discontinuation of PPI therapy for the prevention of CDI, although inappropriate PPI therapy should always be discontinued.11
Advanced age is an important nonmodifiable risk factor for CDI. Older adults who live in long-term care facilities are at a higher risk for CDI, and these facilities have colonization rates as high as 50%.12
Community-associated risk. In an analysis of community-associated cases of CDI, 82% of patients reported some sort of health care exposure (ranging from physician office visit to surgery admission), 64% reported the receipt of antimicrobial therapy, and 31% reported the use of PPIs.14 Inflammatory bowel disease (IBD) may also put community dwellers at higher risk for CDI and its complications.15
CASES 1 & 2
Both CASE patients have risk factors for CDI. Ms. O (CASE 1) is likely at risk for CDI after completion of her recent course of clindamycin. Ms. Z (CASE 2) has several risk factors for recurrent CDI, including advanced age (≥ 65 years), residence in a long-term care facility, prior antibiotic exposure, and immunodeficiency because of chemotherapy/steroid use.
Continue to: Diagnosis
Diagnosis: Who and how to test
CDI should be both a clinical and laboratory-confirmed diagnosis. Patients should be tested for CDI if they have 3 or more episodes of unexplainable, new-onset unformed stools in 24 hours.11 Asymptomatic patients should not be tested to avoid unnecessary testing and treatment of those who are colonized but not infected.11 It is not recommended to routinely test patients who have taken laxatives within the previous 48 hours.11
There are several stool-based laboratory test options for the diagnosis of CDI (TABLE 211,12,16) but no definitive recommendation for all institutions.11 Many institutions have now implemented PCR testing for the diagnosis of CDI. However, while the benefits of this test include reduced need for repeat testing and possible identification of carriers, it’s estimated that reports of CDI increase more than 50% when an institution switches to PCR testing.1 Nonetheless, a one-step, highly sensitive test such as PCR may be used if strict criteria are implemented and followed.
The increase in positive PCR tests has prompted evaluation of using another test in addition to or in place of PCR. Multistep testing options include a glutamate dehydrogenase assay (GDH) with a toxin EIA, GDH with a toxin EIA and final decision via PCR, or PCR with toxin EIA.11 Use of a multistep diagnostic algorithm may increase overall specificity up to 100%, which may improve determination of asymptomatic colonization vs active infection.16 (Patients who have negative toxin results with positive PCR likely have colonization but not infection and often do not require treatment.) IDSA guidelines recommend that the stool toxin test should be part of a multistep algorithm for diagnosis, rather than PCR alone, if strict criteria are not implemented for stool test submission.11
There is no need to perform a test of cure after a patient has been treated for CDI, and no repeat testing should be performed within 7 days of the previous test.11 After successful treatment, patients will continue to shed spores and test positively via PCR for weeks to months.11 When patients have a positive PCR test, there are several important infection control efforts that institutions should consider; see “IDSA weighs in on measures to combat C difficile.”
SIDEBAR
IDSA weighs in on measures to combat C difficile
The spores produced by Clostridioides difficile can survive for 5 months or longer on dry surfaces because of resistance to heat, acid, antibiotics, and many cleaning products.38 Unfortunately, spores transmitted from health care workers and the environment are the most likely cause of infection spreading in health care institutions. To prevent transmission of C difficile infection (CDI) throughout institutions, appropriate infection control measures are necessary.
Clinical practice guidelines from the Infectious Diseases Society of America (IDSA) recommend that patients with CDI be isolated to a private room with a dedicated toilet. Health care staff should wear gloves and gowns when entering the room of, or taking care of, a patient with CDI. For patients who are suspected of having CDI, contact precautions should be implemented while awaiting test results. When the diagnosis is confirmed, contact precautions should remain in place for at least 48 hours after resolution of diarrhea but may be continued until discharge.11
Practicing good hand hygiene is essential, especially in institutions with high rates of CDI or if fecal contamination is likely.11 Hand hygiene with soap and water is preferred, due to evidence of a higher spore removal rate, but alcohol-based alternatives may be used if necessary.11 In institutions with high rates of CDI, terminal (post-discharge) cleaning of rooms with a sporicidal agent should be considered.11
Asymptomatic carriers are also a concern for transmission of CDI in institutional settings. Screening and isolating patients who are carriers may prevent transmission, and some institutions have implemented this process to reduce the risk for CDI that originates in a health care facility.39 The IDSA guidelines do not make a recommendation regarding screening or isolation of asymptomatic carriers, so the decision is institution specific.11 These guidelines also recommend that patients presenting with similar infectious organisms be housed in the same room, if needed, to avoid cross-contamination to others or additional surfaces.11
For pediatric patients, testing recommendations vary by age. Testing is not generally recommended for neonates or infants ≤ 2 years of age with diarrhea because of the prevalence of colonization with C difficile.11 For children older than 2 years, testing for CDI is only recommended in the setting of prolonged or worsening diarrhea and if the patient has risk factors such as IBD, immunocompromised state, health care exposure, or recent antibiotic use.11 In addition, testing in this population should only be considered once other infectious and noninfectious causes of diarrhea have been excluded.11
Continue to: First-line treatment? Drug of choice has changed
First-line treatment? Drug of choice has changed
In 2018, the IDSA published new treatment guidelines that provide important updates from the 2010 guidelines.11 Chief among these was the elimination of metronidazole as a first-line therapy. Vancomycin or fidaxomicin are now recommended as first-line treatment options because of superior eradication of C difficile when compared with metronidazole.11 In the opinion of the authors, vancomycin should be considered the drug of choice because of cost. (See “The case for vancomycin.”)
SIDEBAR
The case for vancomycin
The majority of studies conducted prior to publication of the 2010 Infectious Diseases Society of America guidelines described numerically worse eradication rates of Clostridioides difficile infection (CDI) with metronidazole compared with vancomycin for all severities of infection, but statistical significance was not achieved. These studies also showed a nonsignificant increase in CDI recurrence with metronidazole.17,40,41
A 2005 systematic review demonstrated increased treatment failure rates with metronidazole.42 The rates of metronidazole discontinuation and transition to alternative options more than doubled in 2003-2004, to 25.7% of patients compared with 9.6% in earlier years.42 Metronidazole efficacy was further questioned in a prospective observational study conducted in 2005, in which only 50% of patients were cured after an initial course of treatment, while 28% had recurrence within 90 days.43
Vancomycin was found to be the superior treatment option to metronidazole and tolevamer in a 2014 randomized controlled trial.18 This study also demonstrated that vancomycin was the superior therapy when comparing treatment-naïve vs experienced patients and severity of CDI.18 A 2017 retrospective cohort study demonstrated decreased 30-day all-cause mortality for patients taking vancomycin vs metronidazole (adjusted relative risk = 0.86; 95% confidence interval, 0.74-0.98), although it should be noted that this difference was driven by those with severe CDI, and there was no statistically significant difference in mortality for patients with mild-to-moderate CDI.44
The results of these studies led to the recommendation of vancomycin over metronidazole as first-line pharmacotherapy for CDI in practice, despite the historical perspective that overutilization of oral vancomycin could potentially increase rates of vancomycinresistant Enterococcus.11
Metronidazole should only be used in the treatment of CDI as a lastresort medication because of cost or insurance coverage. Although the price of oral vancomycin is higher, favorable patient outcomes are substantially greater, and recent analyses have shown that vancomycin is actually more cost-effective than metronidazole as a result.24 Adverse effects for metronidazole include neurotoxicity, gastrointestinal discomfort, and disulfiram-like reaction.
Vancomycin does not harbor as many adverse effects because of extremely low systemic absorption when taken orally, but patients may experience gastrointestinal discomfort.45 While systemic exposure with oral administration of vancomycin is very low (< 1%), there have been case reports of nephrotoxicity and “red man syndrome” that are more typically seen with intravenous vancomycin.44
Given the low rate of systemic exposure, routine monitoring of renal function and serum drug levels is not usually necessary during oral vancomycin therapy. However, it may be appropriate to monitor renal function and serum levels of vancomycin in patients who have renal failure, have altered intestinal integrity, are age ≥ 65 years, or are receiving high doses of vancomycin.46
10-day vs 14-day treatment of CDI. Most studies for the treatment of CDI have used a 10-day regimen rather than increasing the duration to a 14-day regimen, and nearly all studies conducted have displayed high rates of symptom resolution at the end of 10 days of treatment.17,18 Thus, treatment duration beyond 10 days should only be considered for patients who continue to have symptoms or complications with CDI on Day 10 of treatment.
First recurrence. Metronidazole is no longer the recommended treatment for first recurrence of CDI treated initially with metronidazole; instead, a 10-day course of vancomycin should be used.11 For recurrent cases in patients initially treated with vancomycin, a tapered and pulsed regimen of vancomycin is recommended11:
- vancomycin PO 125 mg four times daily for 10 to 14 days followed by
- vancomycin PO 125 mg twice daily for 7 days, then
- vancomycin PO 125 mg once daily for 7 days, then
- vancomycin PO 125 mg every 2 to 3 days for 2 to 8 weeks.
Pediatric patients. The IDSA guidelines recommend use of metronidazole or vancomycin to treat an initial case or first recurrence of mild-to-moderate CDI in this population.11 Due to a lack of quality evidence, the drug of choice for initial treatment is inconclusive, so patient-specific factors and cost should be considered when choosing an agent.11 If not cost prohibitive, vancomycin should be the drug of choice for most cases of pediatric CDI, and for severe cases or multiple recurrences of CDI, vancomycin is clearly the drug of choice.
Recommended agents: A closer look
Oral vancomycin products. Vancocin, a capsule, and Firvanq, an oral solution, are 2 vancomycin products currently on the market for CDI. Although the capsules are a readily available treatment option, the cost of the full course of treatment can be a barrier for patients without insurance, or with high copays or deductibles (brand name, $4000; generic, $1252).19
Continue to: Historically, in an effort to keep costs down...
Historically, in an effort to keep costs down, an oral solution was often inexpensively compounded at hospitals or pharmacies.20
Fidaxomicin, an oral macrocyclic antibiotic with minimal systemic absorption, was first approved by the US Food and Drug Administration (FDA) for CDI in 2011.21 The IDSA guidelines recommend fidaxomicin for initial, and recurrent, cases of CDI as an alternative to vancomycin.11 This recommendation is based on 2 randomized double-blind trials comparing fidaxomicin to standard-dose oral vancomycin for initial or recurrent CDI.21,22
Pooled data from these 2 similar studies found that fidaxomicin was noninferior (10% noninferiority margin) to vancomycin for the primary outcome of clinical cure.23 Fidaxomicin was shown to be superior to vancomycin regarding rate of CDI recurrence (relative risk [RR] = 0.61; 95% confidence interval [CI], 0.43-0.87). These results were similar regardless of whether the CDI was an initial or recurrent case.23
Given the lack of systemic absorption, fidaxomicin is generally very well tolerated. The largest downside to fidaxomicin is its cost, which can be nearly $5000 for a standard 10-day course (vs as little as $165 for oral vancomycin).19 As a result, oral vancomycin solution is likely the most cost-effective therapy for initial cases of CDI.24 In patients with poor medication adherence, fidaxomicin offers the advantage of less-frequent dosing (twice daily vs 4 times daily with vancomycin).
For cases of recurrent CDI, when treatment failure occurred with vancomycin, fidaxomicin should be considered as an efficacious alternative. If fidaxomicin is used, it is advisable to verify coverage with the patient’s insurance plan, since prior authorization is frequently required.
Continue to: When meds fail, consider a fecal microbiota transplant
When meds fail, consider a fecal microbiota transplant
Another important change in the IDSA guidelines for CDI management is the strong recommendation for fecal microbiota transplantation (FMT) in patients with multiple recurrences of CDI for whom appropriate antibiotic treatment courses have failed.11,25 The goal of FMT is to “normalize” an abnormal gut microbiome by transplanting donor stool into a recipient.26
FMT has been shown to be highly effective in 5 randomized clinical trials conducted since 2013, with CDI cure rates between 85% and 94%.11 This rate of cure is particularly impressive given that the studies only included patients with refractory CDI.
Patients with recurrent CDI who may be candidates for FMT should be referred to a center or specialist with experience in FMT. These transplants can be expensive because of the screening process involved in obtaining donor samples. (Historically, a single FMT has cost $3000-$5000, and it is seldom covered by insurance.27) The emergence of universal stool banks offers a streamlined solution to this process.26
Fresh or frozen stool is considered equally effective in treating refractory CDI.26 Oral capsule and freeze-dried stool formulations have been studied, but their use is considered investigational at this time.26
Delivery via colonoscopy to the right colon is the preferred route of infusion; however, delivery via enema or nasogastric, nasojejunal, or nasoduodenal infusion can be considered as well.26
Continue to: In preparing for stool transplantation...
In preparing for stool transplantation, patients should be treated with standard doses of oral vancomycin or fidaxomicin for 3 days before the procedure to suppress intestinal C difficile, and the last dose of antibiotics should be given 12 to 48 hours before the procedure.26 Bowel lavage with polyethylene glycol is recommended, regardless of whether stool is delivered via colonoscopy or upper GI route.
Short-term adverse events associated with FMT appear to be minimal; data is lacking for long-term safety outcomes.28 While only recommended currently for cases of recurrent CDI, there is promising data emerging for use of FMT for severe cases, even without recurrence.29
The role of probiotics remains unclear
Probiotics have been explored in numerous trials to determine if they are effective in preventing CDI in patients who have been prescribed antibiotics.11 While no randomized trials have conclusively shown benefit, several meta-analyses have shown that the use of probiotics may result in a 60% to 65% relative risk reduction in CDI incidence.30,31
One proviso to these meta-analyses is that the incorporated studies have typically included patients at very high risk for CDI, and subanalyses have only found a reduction in CDI incidence when patients are at a very high baseline risk. In addition, there are many differences in probiotic types, formulations, treatment durations, and follow-up. As a result, the IDSA guidelines state that there is “insufficient data at this time” to recommend routine administration of probiotics for either primary or secondary CDI prophylaxis.11
Due to insufficient high-quality data, the IDSA guidelines do not provide a recommendation regarding use as an adjunct treatment option for acute CDI.11 Probiotics should not be routinely used to prevent CDI; however, they may provide benefit if reserved for patients at the highest risk for CDI (eg, history of CDI, prolonged use of broad-spectrum antibiotics, high local incidence).
Continue to: What about surgical intervention?
What about surgical intervention?
In severe cases of CDI, surgery may be necessary and can reduce mortality.32 The surgical procedure with the strongest recommendation in the IDSA guidelines is the subtotal colectomy, though the diverting loop ileostomy is an alternative option.11 Patients who may benefit from surgery include those with a WBC count ≥ 25,000; lactate > 5 mmol/L11; altered mental status; megacolon; perforation of the colon; acute abdomen on physical examination; or septic shock due to CDI.33 Although surgery can be beneficial, the mortality rate remains high for those with CDI who undergo colectomy.33
Reserve bezlotoxumab for prevention of recurrence
Bezlotoxumab, a human monoclonal immunoglobulin GI/kappa antibody, was approved by the FDA in 2016 for the prevention of recurrent CDI. Its mechanism of action is to bind and neutralize C difficile toxin B. It was approved as a single infusion for adults who are receiving active antibiotic therapy for CDI and are considered to be at high risk for recurrence.34
This approval was based on 2 trials of more than 2500 patients, in which participants received bezlotoxumab or placebo while receiving treatment for primary or recurrent CDI. The primary outcome of these studies was recurrent infection within 12 weeks after infusion, which was significantly lower for bezlotoxumab in both studies: 17% vs 28% (P < 0.001) in one trial and 16% vs 26% (P < 0.001) in the other trial.35
Bezlotoxumab should only be used as an adjunct to prevent recurrence.32 There is no recommendation for or against bezlotoxumab in the IDSA guidelines because of the recent date of the drug’s approval. Its frequency of use will likely depend on the number of patients who meet criteria as high risk for recurrence and its estimated cost of $4560 per dose.34,36
CASES
CASE 1: In light of Ms. O’s recent completion of a course of clindamycin and unremarkable lab work, she should be treated for mild-to-moderate CDI. She has no comorbid conditions to warrant fidaxomicin, and thus vancomycin (capsules or oral solution) would be the best treatment option. Ms. O is started on vancomycin PO 125 mg qid for 10 days. She is also advised to discontinue loperamide as soon as possible, based on poor outcomes data seen with the use of antimotility agents in CDI.37
Continue to: CASE 2
CASE 2: Ms. Z has several risk factors for recurrent CDI and has an elevated WBC count and SCr level (WBC ≥ 15,000 and SCr > 1.5 mg/dL). Thus, she is classified as having severe, recurrent CDI. Oral levofloxacin and metronidazole should be discontinued, because they increase the risk for treatment failure and development of more virulent CDI strains, such as BI/NAP1/027. Since Ms. Z used metronidazole for treatment of her initial CDI, vancomycin or fidaxomicin should be used at this time. Either vancomycin PO 125 mg qid for 10 days or fidaxomicin 200 mg bid for 10 days would be an appropriate regimen; however, because of cost and unknown insurance coverage, vancomycin is the most appropriate regimen.
CORRESPONDENCE
Jeremy Vandiver, PharmD, BCPS, University of Wyoming School of Pharmacy, Saint Joseph Family Medicine Residency, 1000 E. University Avenue, Dept 3375, Laramie, WY 82071; [email protected]
1. Polage CR, Gyorke CE, Kennedy MA, et al. Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med. 2015;175:1792-1801.
2. Reveles KR, Lee GC, Boyd NK, et al. The rise in Clostridium difficile infection incidence among hospitalized adults in the United States: 2001-2010. Am J Infect Control. 2014;42:1028-1032.
3. Dubberke ER, Olsen MA. Burden of Clostridium difficile on the healthcare system. Clin Infect Dis. 2012;55(suppl 2):S88-S92.
4. Tariq R, Singh S, Gupta A, et al. Association of gastric acid suppression with recurrent Clostridium difficile infection: a systematic review and meta-analysis. JAMA Intern Med. 2017;177:784-791.
5. Kachrimanidou M, Malisiovas N. Clostridium difficile infection: a comprehensive review. Crit Rev Microbiol. 2011;37:178-187.
6. O’Connor JR, Johnson S, Gerding DN. Clostridium difficile infection caused by the epidemic BI/NAP1/027 strain. Gastroenterology. 2009;136:1913-1924.
7. Kelly CP. A 76-year-old man with recurrent Clostridium difficile-associated diarrhea: review of C difficile infection. JAMA. 2009;301:954-962.
8. Cornely OA, Miller MA, Louie TJ, et al. Treatment of first recurrence of Clostridium difficile infection: fidaxomicin versus vancomycin. Clin Infect Dis. 2012;55(suppl 2):S154-S161.
9. Napolitano LM, Edmiston CE Jr. Clostridium difficile disease: diagnosis, pathogenesis, and treatment update. Surgery 2017;162:325-348.
10. Deshpande A, Pasupuleti V, Thota P, et al. Risk factors for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol. 2015;36:452-460.
11. McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66:e1-e48.
12. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108:478-498; quiz 499.
13. Seto CT, Jeraldo P, Orenstein R, et al. Prolonged use of a proton pump inhibitor reduces microbial diversity: implications for Clostridium difficile susceptibility. Microbiome. 2014;2:42.
14. Chitnis AS, Holzbauer SM, Belflower RM, et al. Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. JAMA Intern Med. 2013;173:1359-1367.
15. Negrón ME, Rezaie A, Barkema HW, et al. Ulcerative colitis patients with Clostridium difficile are at increased risk of death, colectomy, and postoperative complications: a population-based inception cohort study. Am J Gastroenterol. 2016;111:691-704.
16. Bagdasarian N, Rao K, Malani PN. Diagnosis and treatment of Clostridium difficile in adults: a systematic review. JAMA. 2015;313:398-408.
17. Zar FA, Bakkanagari SR, Moorthi KM, et al. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45:302-307.
18. Johnson S, Louie TJ, Gerding DN, et al. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014;59:345-354.
19. Vancomycin: product details. Redbook Online. www.micromedexsolutions.com. Published 2018. Accessed June 13, 2020.
20. Mergenhagen KA, Wojciechowski AL, Paladino JA. A review of the economics of treating Clostridium difficile infection. Pharmacoeconomics. 2014;32:639-650.
21. Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422-431.
22. Cornely OA, Crook DW, Esposito R, et al. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis. 2012;12:281-289.
23. Crook DW, Walker AS, Kean Y, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials. Clin Infect Dis. 2012;55 suppl 2:S93-103.
24. Ford DC, Schroeder MC, Ince D, et al. Cost-effectiveness analysis of initial treatment strategies for mild-to-moderate Clostridium difficile infection in hospitalized patients. Am J Health Syst Pharm. 2018;75:1110-1121.
25. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31:431-455.
26. Panchal P, Budree S, Scheeler A, et al. Scaling safe access to fecal microbiota transplantation: past, present, and future. Curr Gastroenterol Rep. 2018;20:14.
27. Arbel LT, Hsu E, McNally K. Cost-effectiveness of fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection: a literature review. Cureus. 2017;9:e1599.
28. Cammarota G, Ianiro G, Tilg H, et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017;66:569-580.
29. Hocquart M, Lagier JC, Cassir N, et al. Early fecal microbiota transplantation improves survival in severe Clostridium difficile infections. Clin Infect Dis. 2018;66:645-650.
30. Goldenberg JZ, Yap C, Lytvyn L, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017;12:CD006095.
31. Johnston BC, Lytvyn L, Lo CK, et al. Microbial preparations (probiotics) for the prevention of Clostridium difficile infection in adults and children: an individual patient data meta-analysis of 6,851 participants. Infect Control Hosp Epidemiol. 2018:1-11.
32. Stewart DB, Hollenbeak CS, Wilson MZ. Is colectomy for fulminant Clostridium difficile colitis life saving? A systematic review. Colorectal Dis. 2013;15:798-804.
33. Julien M, Wild JL, Blansfield J, et al. Severe complicated Clostridium difficile infection: can the UPMC proposed scoring system predict the need for surgery? J Trauma Acute Care Surg. 2016;81:221-228.
34. Merck & Co, Inc. Sharp M. ZinplavaTM (bezlotoxumab [package insert] US Food and Drug Administration Web site. www.accessdata.fda.gov/drugsatfda_docs/label/2016/761046s000lbl.pdf. Revised October 2016. Accessed May 29, 2020.
35. Wilcox MH, Gerding DN, Poxton IR, et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376:305-317.
36. Chahine EB, Cho JC, Worley MV. Bezlotoxumab for the Prevention of Clostridium difficile recurrence. Consult Pharm. 2018;33:89-97.
37. Koo HL, Koo DC, Musher DM, et al. Antimotility agents for the treatment of Clostridium difficile diarrhea and colitis. Clin Infect Dis. 2009;48:598-605.
38. Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol. 2009;7:526-536.
39. Longtin Y, Paquet-Bolduc B, Gilca R, et al. Effect of detecting and isolating Clostridium difficile carriers at hospital admission on the incidence of C difficile infections: a quasi-experimental controlled study. JAMA Intern Med. 2016;176:796-804.
40. Teasley DG, Gerding DN, Olson MM, et al. Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet. 1983;2:1043-1046.
41. Wenisch C, Parschalk B, Hasenhündl M, et al. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis. 1996;22:813-818.
42. Pepin J, Alary ME, Valiquette L, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis. 2005;40:1591-1597.
43. Musher DM, Aslam S, Logan N, et al. Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis. 2005;40:1586-1590.
44. Stevens VW, Nelson RE, Schwab-Daugherty EM, et al. Comparative effectiveness of vancomycin and metronidazole for the prevention of recurrence and death in patients with Clostridium difficile infection. JAMA Intern Med. 2017;177:546-553.
45. CutisPharma. FirvanqTM (vancomycin hydrochloride) for oral solution [package insert]. US Food and Drug Administration Web site. www.accessdata.fda.gov/drugsatfda_docs/label/2018/208910s000lbl.pdf. Revised January 2018. Accessed May 29, 2020.
46.
CASE 1
Beth O, a 63-year-old woman, presents to the emergency department (ED) with a 2-week history of diarrhea (6 very loose, watery stools per day) and lower abdominal pain. The patient denies any vomiting, sick contacts, or recent travel. Past medical history includes varicose veins. Her only active medication is loperamide, as needed, for the past 2 weeks. Ms. O also recently completed a 10-day course of clindamycin for an infected laceration on her finger.
Ms. O’s laboratory values are unremarkable, with a normal white blood cell (WBC) count and serum creatinine (SCr) level. Abdominal computed tomography (CT) reveals some abnormal bowel dilatation and a slight increase in colon wall thickness. There is a high suspicion for Clostridioides difficile (formerly Clostridium difficile) infection (CDI), and stool sent for polymerase chain reaction (PCR) testing comes back positive for C difficile toxin B. It is revealed to be a strain other than the BI/NAP1/027 epidemic strain (which has a higher mortality rate).
How should this patient be treated?
CASE 2
Sixty-eight-year-old Barbara Z presents to the ED from her skilled nursing facility with persistent diarrhea and abdominal cramping. She was diagnosed with CDI about 2 months ago and reports that her symptoms resolved within 4 to 5 days after starting a 14-day course of oral metronidazole.
Her past medical history is notable for multiple myeloma with bone metastasis, for which she is actively undergoing chemotherapy treatment. She also has chronic kidney disease (baseline SCr, 2.2 mg/dL), hypertension, and anemia of chronic disease. The patient’s medications include amlodipine and cholecalciferol. Her chemotherapy regimen consists of bortezomib, lenalidomide, and dexamethasone. CT of the abdomen shows diffuse colon wall thickening with surrounding inflammatory stranding—concerning for pancolitis. There is no evidence of toxic megacolon or ileus.
Ms. Z’s laboratory values are notable for a WBC count of 15,900 cells/mL and an SCr of 4.1 mg/dL. She is started on oral levofloxacin and metronidazole due to concern for an intra-abdominal infection. PCR testing is positive for C difficile, and an enzyme immunoassay (EIA) for C difficile toxin is positive.
What factors put Ms. Z at risk for C difficile, and how should she be treated?
Continue to: C difficile is one of the most...
C difficile is one of the most commonly reported pathogens in health care–associated infections and affects almost 1% of all hospitalized patients in the United States each year.1 From 2001 to 2010, the incidence of CDI doubled in patients discharged from hospitals,2 with an estimated cost of more than $5 billion annually.3 Furthermore, rates of community-associated CDI continue to increase and account for about 40% of cases.4
After colonization in the intestine, C difficile releases 2 toxins (TcdA and TcdB) that cause colitis.5 Patients may present with mild diarrhea that can progress to abdominal pain, cramping, fever, and leukocytosis. Fulminant CDI can lead to the formation of pseudomembranes in the colon, toxic megacolon, bowel perforation, shock, and death.2
Beginning in the early 2000s, hospitals reported increases in severe cases of CDI.6 A specific strain known as BI/NAP1/027 was identified and characterized by fluoroquinolone resistance, increased spore formation, and a higher mortality rate.6
Further complicating matters … Recurrent CDI occurs in up to 10% to 30% of patients,7 typically within 14 to 45 days of completion of antibiotic pharmacotherapy for CDI.8 Recurrence is characterized by new-onset diarrhea or abdominal symptoms after completion of treatment for CDI.5
It typically begins with an antibiotic
Risk factors for CDI are listed in TABLE 1.9 The most important modifiable risk factor for initial and recurrent CDI is recent use of antibiotics.10 Most antibiotics can disrupt normal intestinal flora, causing colonization of C difficile, but the strongest association seems to be with third- and fourth-generation cephalosporins, fluoroquinolones, carbapenems, and clindamycin.11 The risk for CDI occurs during antibiotic treatment, as well as up to 3 months after completion of antibiotic therapy.7 Exposure to multiple antibiotics and extended duration of antibacterial therapy can greatly increase the risk for CDI, so antimicrobial stewardship is key.11
Continue to: Continuing antibiotics while attempting...
Continuing antibiotics while attempting to treat CDI reduces the patient’s clinical response to CDI treatment, which can lead to recurrence.12 The Infectious Diseases Society of America (IDSA) guidelines include a strong recommendation to discontinue concurrent antibiotics as soon as possible in these scenarios.11
Acid-suppression therapy has also been associated with CDI. The mechanism is thought to be an interruption in the protection provided by stomach acid, and use over time may reduce the diversity of flora within the gut microbiome.13 The data demonstrating an association between acid-suppression therapy and CDI is conflicting, which may be a result of confounding factors such as the severity of CDI illness and diarrhea induced by use of proton pump inhibitors (PPIs).4 IDSA guidelines do not provide a recommendation regarding discontinuation of PPI therapy for the prevention of CDI, although inappropriate PPI therapy should always be discontinued.11
Advanced age is an important nonmodifiable risk factor for CDI. Older adults who live in long-term care facilities are at a higher risk for CDI, and these facilities have colonization rates as high as 50%.12
Community-associated risk. In an analysis of community-associated cases of CDI, 82% of patients reported some sort of health care exposure (ranging from physician office visit to surgery admission), 64% reported the receipt of antimicrobial therapy, and 31% reported the use of PPIs.14 Inflammatory bowel disease (IBD) may also put community dwellers at higher risk for CDI and its complications.15
CASES 1 & 2
Both CASE patients have risk factors for CDI. Ms. O (CASE 1) is likely at risk for CDI after completion of her recent course of clindamycin. Ms. Z (CASE 2) has several risk factors for recurrent CDI, including advanced age (≥ 65 years), residence in a long-term care facility, prior antibiotic exposure, and immunodeficiency because of chemotherapy/steroid use.
Continue to: Diagnosis
Diagnosis: Who and how to test
CDI should be both a clinical and laboratory-confirmed diagnosis. Patients should be tested for CDI if they have 3 or more episodes of unexplainable, new-onset unformed stools in 24 hours.11 Asymptomatic patients should not be tested to avoid unnecessary testing and treatment of those who are colonized but not infected.11 It is not recommended to routinely test patients who have taken laxatives within the previous 48 hours.11
There are several stool-based laboratory test options for the diagnosis of CDI (TABLE 211,12,16) but no definitive recommendation for all institutions.11 Many institutions have now implemented PCR testing for the diagnosis of CDI. However, while the benefits of this test include reduced need for repeat testing and possible identification of carriers, it’s estimated that reports of CDI increase more than 50% when an institution switches to PCR testing.1 Nonetheless, a one-step, highly sensitive test such as PCR may be used if strict criteria are implemented and followed.
The increase in positive PCR tests has prompted evaluation of using another test in addition to or in place of PCR. Multistep testing options include a glutamate dehydrogenase assay (GDH) with a toxin EIA, GDH with a toxin EIA and final decision via PCR, or PCR with toxin EIA.11 Use of a multistep diagnostic algorithm may increase overall specificity up to 100%, which may improve determination of asymptomatic colonization vs active infection.16 (Patients who have negative toxin results with positive PCR likely have colonization but not infection and often do not require treatment.) IDSA guidelines recommend that the stool toxin test should be part of a multistep algorithm for diagnosis, rather than PCR alone, if strict criteria are not implemented for stool test submission.11
There is no need to perform a test of cure after a patient has been treated for CDI, and no repeat testing should be performed within 7 days of the previous test.11 After successful treatment, patients will continue to shed spores and test positively via PCR for weeks to months.11 When patients have a positive PCR test, there are several important infection control efforts that institutions should consider; see “IDSA weighs in on measures to combat C difficile.”
SIDEBAR
IDSA weighs in on measures to combat C difficile
The spores produced by Clostridioides difficile can survive for 5 months or longer on dry surfaces because of resistance to heat, acid, antibiotics, and many cleaning products.38 Unfortunately, spores transmitted from health care workers and the environment are the most likely cause of infection spreading in health care institutions. To prevent transmission of C difficile infection (CDI) throughout institutions, appropriate infection control measures are necessary.
Clinical practice guidelines from the Infectious Diseases Society of America (IDSA) recommend that patients with CDI be isolated to a private room with a dedicated toilet. Health care staff should wear gloves and gowns when entering the room of, or taking care of, a patient with CDI. For patients who are suspected of having CDI, contact precautions should be implemented while awaiting test results. When the diagnosis is confirmed, contact precautions should remain in place for at least 48 hours after resolution of diarrhea but may be continued until discharge.11
Practicing good hand hygiene is essential, especially in institutions with high rates of CDI or if fecal contamination is likely.11 Hand hygiene with soap and water is preferred, due to evidence of a higher spore removal rate, but alcohol-based alternatives may be used if necessary.11 In institutions with high rates of CDI, terminal (post-discharge) cleaning of rooms with a sporicidal agent should be considered.11
Asymptomatic carriers are also a concern for transmission of CDI in institutional settings. Screening and isolating patients who are carriers may prevent transmission, and some institutions have implemented this process to reduce the risk for CDI that originates in a health care facility.39 The IDSA guidelines do not make a recommendation regarding screening or isolation of asymptomatic carriers, so the decision is institution specific.11 These guidelines also recommend that patients presenting with similar infectious organisms be housed in the same room, if needed, to avoid cross-contamination to others or additional surfaces.11
For pediatric patients, testing recommendations vary by age. Testing is not generally recommended for neonates or infants ≤ 2 years of age with diarrhea because of the prevalence of colonization with C difficile.11 For children older than 2 years, testing for CDI is only recommended in the setting of prolonged or worsening diarrhea and if the patient has risk factors such as IBD, immunocompromised state, health care exposure, or recent antibiotic use.11 In addition, testing in this population should only be considered once other infectious and noninfectious causes of diarrhea have been excluded.11
Continue to: First-line treatment? Drug of choice has changed
First-line treatment? Drug of choice has changed
In 2018, the IDSA published new treatment guidelines that provide important updates from the 2010 guidelines.11 Chief among these was the elimination of metronidazole as a first-line therapy. Vancomycin or fidaxomicin are now recommended as first-line treatment options because of superior eradication of C difficile when compared with metronidazole.11 In the opinion of the authors, vancomycin should be considered the drug of choice because of cost. (See “The case for vancomycin.”)
SIDEBAR
The case for vancomycin
The majority of studies conducted prior to publication of the 2010 Infectious Diseases Society of America guidelines described numerically worse eradication rates of Clostridioides difficile infection (CDI) with metronidazole compared with vancomycin for all severities of infection, but statistical significance was not achieved. These studies also showed a nonsignificant increase in CDI recurrence with metronidazole.17,40,41
A 2005 systematic review demonstrated increased treatment failure rates with metronidazole.42 The rates of metronidazole discontinuation and transition to alternative options more than doubled in 2003-2004, to 25.7% of patients compared with 9.6% in earlier years.42 Metronidazole efficacy was further questioned in a prospective observational study conducted in 2005, in which only 50% of patients were cured after an initial course of treatment, while 28% had recurrence within 90 days.43
Vancomycin was found to be the superior treatment option to metronidazole and tolevamer in a 2014 randomized controlled trial.18 This study also demonstrated that vancomycin was the superior therapy when comparing treatment-naïve vs experienced patients and severity of CDI.18 A 2017 retrospective cohort study demonstrated decreased 30-day all-cause mortality for patients taking vancomycin vs metronidazole (adjusted relative risk = 0.86; 95% confidence interval, 0.74-0.98), although it should be noted that this difference was driven by those with severe CDI, and there was no statistically significant difference in mortality for patients with mild-to-moderate CDI.44
The results of these studies led to the recommendation of vancomycin over metronidazole as first-line pharmacotherapy for CDI in practice, despite the historical perspective that overutilization of oral vancomycin could potentially increase rates of vancomycinresistant Enterococcus.11
Metronidazole should only be used in the treatment of CDI as a lastresort medication because of cost or insurance coverage. Although the price of oral vancomycin is higher, favorable patient outcomes are substantially greater, and recent analyses have shown that vancomycin is actually more cost-effective than metronidazole as a result.24 Adverse effects for metronidazole include neurotoxicity, gastrointestinal discomfort, and disulfiram-like reaction.
Vancomycin does not harbor as many adverse effects because of extremely low systemic absorption when taken orally, but patients may experience gastrointestinal discomfort.45 While systemic exposure with oral administration of vancomycin is very low (< 1%), there have been case reports of nephrotoxicity and “red man syndrome” that are more typically seen with intravenous vancomycin.44
Given the low rate of systemic exposure, routine monitoring of renal function and serum drug levels is not usually necessary during oral vancomycin therapy. However, it may be appropriate to monitor renal function and serum levels of vancomycin in patients who have renal failure, have altered intestinal integrity, are age ≥ 65 years, or are receiving high doses of vancomycin.46
10-day vs 14-day treatment of CDI. Most studies for the treatment of CDI have used a 10-day regimen rather than increasing the duration to a 14-day regimen, and nearly all studies conducted have displayed high rates of symptom resolution at the end of 10 days of treatment.17,18 Thus, treatment duration beyond 10 days should only be considered for patients who continue to have symptoms or complications with CDI on Day 10 of treatment.
First recurrence. Metronidazole is no longer the recommended treatment for first recurrence of CDI treated initially with metronidazole; instead, a 10-day course of vancomycin should be used.11 For recurrent cases in patients initially treated with vancomycin, a tapered and pulsed regimen of vancomycin is recommended11:
- vancomycin PO 125 mg four times daily for 10 to 14 days followed by
- vancomycin PO 125 mg twice daily for 7 days, then
- vancomycin PO 125 mg once daily for 7 days, then
- vancomycin PO 125 mg every 2 to 3 days for 2 to 8 weeks.
Pediatric patients. The IDSA guidelines recommend use of metronidazole or vancomycin to treat an initial case or first recurrence of mild-to-moderate CDI in this population.11 Due to a lack of quality evidence, the drug of choice for initial treatment is inconclusive, so patient-specific factors and cost should be considered when choosing an agent.11 If not cost prohibitive, vancomycin should be the drug of choice for most cases of pediatric CDI, and for severe cases or multiple recurrences of CDI, vancomycin is clearly the drug of choice.
Recommended agents: A closer look
Oral vancomycin products. Vancocin, a capsule, and Firvanq, an oral solution, are 2 vancomycin products currently on the market for CDI. Although the capsules are a readily available treatment option, the cost of the full course of treatment can be a barrier for patients without insurance, or with high copays or deductibles (brand name, $4000; generic, $1252).19
Continue to: Historically, in an effort to keep costs down...
Historically, in an effort to keep costs down, an oral solution was often inexpensively compounded at hospitals or pharmacies.20
Fidaxomicin, an oral macrocyclic antibiotic with minimal systemic absorption, was first approved by the US Food and Drug Administration (FDA) for CDI in 2011.21 The IDSA guidelines recommend fidaxomicin for initial, and recurrent, cases of CDI as an alternative to vancomycin.11 This recommendation is based on 2 randomized double-blind trials comparing fidaxomicin to standard-dose oral vancomycin for initial or recurrent CDI.21,22
Pooled data from these 2 similar studies found that fidaxomicin was noninferior (10% noninferiority margin) to vancomycin for the primary outcome of clinical cure.23 Fidaxomicin was shown to be superior to vancomycin regarding rate of CDI recurrence (relative risk [RR] = 0.61; 95% confidence interval [CI], 0.43-0.87). These results were similar regardless of whether the CDI was an initial or recurrent case.23
Given the lack of systemic absorption, fidaxomicin is generally very well tolerated. The largest downside to fidaxomicin is its cost, which can be nearly $5000 for a standard 10-day course (vs as little as $165 for oral vancomycin).19 As a result, oral vancomycin solution is likely the most cost-effective therapy for initial cases of CDI.24 In patients with poor medication adherence, fidaxomicin offers the advantage of less-frequent dosing (twice daily vs 4 times daily with vancomycin).
For cases of recurrent CDI, when treatment failure occurred with vancomycin, fidaxomicin should be considered as an efficacious alternative. If fidaxomicin is used, it is advisable to verify coverage with the patient’s insurance plan, since prior authorization is frequently required.
Continue to: When meds fail, consider a fecal microbiota transplant
When meds fail, consider a fecal microbiota transplant
Another important change in the IDSA guidelines for CDI management is the strong recommendation for fecal microbiota transplantation (FMT) in patients with multiple recurrences of CDI for whom appropriate antibiotic treatment courses have failed.11,25 The goal of FMT is to “normalize” an abnormal gut microbiome by transplanting donor stool into a recipient.26
FMT has been shown to be highly effective in 5 randomized clinical trials conducted since 2013, with CDI cure rates between 85% and 94%.11 This rate of cure is particularly impressive given that the studies only included patients with refractory CDI.
Patients with recurrent CDI who may be candidates for FMT should be referred to a center or specialist with experience in FMT. These transplants can be expensive because of the screening process involved in obtaining donor samples. (Historically, a single FMT has cost $3000-$5000, and it is seldom covered by insurance.27) The emergence of universal stool banks offers a streamlined solution to this process.26
Fresh or frozen stool is considered equally effective in treating refractory CDI.26 Oral capsule and freeze-dried stool formulations have been studied, but their use is considered investigational at this time.26
Delivery via colonoscopy to the right colon is the preferred route of infusion; however, delivery via enema or nasogastric, nasojejunal, or nasoduodenal infusion can be considered as well.26
Continue to: In preparing for stool transplantation...
In preparing for stool transplantation, patients should be treated with standard doses of oral vancomycin or fidaxomicin for 3 days before the procedure to suppress intestinal C difficile, and the last dose of antibiotics should be given 12 to 48 hours before the procedure.26 Bowel lavage with polyethylene glycol is recommended, regardless of whether stool is delivered via colonoscopy or upper GI route.
Short-term adverse events associated with FMT appear to be minimal; data is lacking for long-term safety outcomes.28 While only recommended currently for cases of recurrent CDI, there is promising data emerging for use of FMT for severe cases, even without recurrence.29
The role of probiotics remains unclear
Probiotics have been explored in numerous trials to determine if they are effective in preventing CDI in patients who have been prescribed antibiotics.11 While no randomized trials have conclusively shown benefit, several meta-analyses have shown that the use of probiotics may result in a 60% to 65% relative risk reduction in CDI incidence.30,31
One proviso to these meta-analyses is that the incorporated studies have typically included patients at very high risk for CDI, and subanalyses have only found a reduction in CDI incidence when patients are at a very high baseline risk. In addition, there are many differences in probiotic types, formulations, treatment durations, and follow-up. As a result, the IDSA guidelines state that there is “insufficient data at this time” to recommend routine administration of probiotics for either primary or secondary CDI prophylaxis.11
Due to insufficient high-quality data, the IDSA guidelines do not provide a recommendation regarding use as an adjunct treatment option for acute CDI.11 Probiotics should not be routinely used to prevent CDI; however, they may provide benefit if reserved for patients at the highest risk for CDI (eg, history of CDI, prolonged use of broad-spectrum antibiotics, high local incidence).
Continue to: What about surgical intervention?
What about surgical intervention?
In severe cases of CDI, surgery may be necessary and can reduce mortality.32 The surgical procedure with the strongest recommendation in the IDSA guidelines is the subtotal colectomy, though the diverting loop ileostomy is an alternative option.11 Patients who may benefit from surgery include those with a WBC count ≥ 25,000; lactate > 5 mmol/L11; altered mental status; megacolon; perforation of the colon; acute abdomen on physical examination; or septic shock due to CDI.33 Although surgery can be beneficial, the mortality rate remains high for those with CDI who undergo colectomy.33
Reserve bezlotoxumab for prevention of recurrence
Bezlotoxumab, a human monoclonal immunoglobulin GI/kappa antibody, was approved by the FDA in 2016 for the prevention of recurrent CDI. Its mechanism of action is to bind and neutralize C difficile toxin B. It was approved as a single infusion for adults who are receiving active antibiotic therapy for CDI and are considered to be at high risk for recurrence.34
This approval was based on 2 trials of more than 2500 patients, in which participants received bezlotoxumab or placebo while receiving treatment for primary or recurrent CDI. The primary outcome of these studies was recurrent infection within 12 weeks after infusion, which was significantly lower for bezlotoxumab in both studies: 17% vs 28% (P < 0.001) in one trial and 16% vs 26% (P < 0.001) in the other trial.35
Bezlotoxumab should only be used as an adjunct to prevent recurrence.32 There is no recommendation for or against bezlotoxumab in the IDSA guidelines because of the recent date of the drug’s approval. Its frequency of use will likely depend on the number of patients who meet criteria as high risk for recurrence and its estimated cost of $4560 per dose.34,36
CASES
CASE 1: In light of Ms. O’s recent completion of a course of clindamycin and unremarkable lab work, she should be treated for mild-to-moderate CDI. She has no comorbid conditions to warrant fidaxomicin, and thus vancomycin (capsules or oral solution) would be the best treatment option. Ms. O is started on vancomycin PO 125 mg qid for 10 days. She is also advised to discontinue loperamide as soon as possible, based on poor outcomes data seen with the use of antimotility agents in CDI.37
Continue to: CASE 2
CASE 2: Ms. Z has several risk factors for recurrent CDI and has an elevated WBC count and SCr level (WBC ≥ 15,000 and SCr > 1.5 mg/dL). Thus, she is classified as having severe, recurrent CDI. Oral levofloxacin and metronidazole should be discontinued, because they increase the risk for treatment failure and development of more virulent CDI strains, such as BI/NAP1/027. Since Ms. Z used metronidazole for treatment of her initial CDI, vancomycin or fidaxomicin should be used at this time. Either vancomycin PO 125 mg qid for 10 days or fidaxomicin 200 mg bid for 10 days would be an appropriate regimen; however, because of cost and unknown insurance coverage, vancomycin is the most appropriate regimen.
CORRESPONDENCE
Jeremy Vandiver, PharmD, BCPS, University of Wyoming School of Pharmacy, Saint Joseph Family Medicine Residency, 1000 E. University Avenue, Dept 3375, Laramie, WY 82071; [email protected]
CASE 1
Beth O, a 63-year-old woman, presents to the emergency department (ED) with a 2-week history of diarrhea (6 very loose, watery stools per day) and lower abdominal pain. The patient denies any vomiting, sick contacts, or recent travel. Past medical history includes varicose veins. Her only active medication is loperamide, as needed, for the past 2 weeks. Ms. O also recently completed a 10-day course of clindamycin for an infected laceration on her finger.
Ms. O’s laboratory values are unremarkable, with a normal white blood cell (WBC) count and serum creatinine (SCr) level. Abdominal computed tomography (CT) reveals some abnormal bowel dilatation and a slight increase in colon wall thickness. There is a high suspicion for Clostridioides difficile (formerly Clostridium difficile) infection (CDI), and stool sent for polymerase chain reaction (PCR) testing comes back positive for C difficile toxin B. It is revealed to be a strain other than the BI/NAP1/027 epidemic strain (which has a higher mortality rate).
How should this patient be treated?
CASE 2
Sixty-eight-year-old Barbara Z presents to the ED from her skilled nursing facility with persistent diarrhea and abdominal cramping. She was diagnosed with CDI about 2 months ago and reports that her symptoms resolved within 4 to 5 days after starting a 14-day course of oral metronidazole.
Her past medical history is notable for multiple myeloma with bone metastasis, for which she is actively undergoing chemotherapy treatment. She also has chronic kidney disease (baseline SCr, 2.2 mg/dL), hypertension, and anemia of chronic disease. The patient’s medications include amlodipine and cholecalciferol. Her chemotherapy regimen consists of bortezomib, lenalidomide, and dexamethasone. CT of the abdomen shows diffuse colon wall thickening with surrounding inflammatory stranding—concerning for pancolitis. There is no evidence of toxic megacolon or ileus.
Ms. Z’s laboratory values are notable for a WBC count of 15,900 cells/mL and an SCr of 4.1 mg/dL. She is started on oral levofloxacin and metronidazole due to concern for an intra-abdominal infection. PCR testing is positive for C difficile, and an enzyme immunoassay (EIA) for C difficile toxin is positive.
What factors put Ms. Z at risk for C difficile, and how should she be treated?
Continue to: C difficile is one of the most...
C difficile is one of the most commonly reported pathogens in health care–associated infections and affects almost 1% of all hospitalized patients in the United States each year.1 From 2001 to 2010, the incidence of CDI doubled in patients discharged from hospitals,2 with an estimated cost of more than $5 billion annually.3 Furthermore, rates of community-associated CDI continue to increase and account for about 40% of cases.4
After colonization in the intestine, C difficile releases 2 toxins (TcdA and TcdB) that cause colitis.5 Patients may present with mild diarrhea that can progress to abdominal pain, cramping, fever, and leukocytosis. Fulminant CDI can lead to the formation of pseudomembranes in the colon, toxic megacolon, bowel perforation, shock, and death.2
Beginning in the early 2000s, hospitals reported increases in severe cases of CDI.6 A specific strain known as BI/NAP1/027 was identified and characterized by fluoroquinolone resistance, increased spore formation, and a higher mortality rate.6
Further complicating matters … Recurrent CDI occurs in up to 10% to 30% of patients,7 typically within 14 to 45 days of completion of antibiotic pharmacotherapy for CDI.8 Recurrence is characterized by new-onset diarrhea or abdominal symptoms after completion of treatment for CDI.5
It typically begins with an antibiotic
Risk factors for CDI are listed in TABLE 1.9 The most important modifiable risk factor for initial and recurrent CDI is recent use of antibiotics.10 Most antibiotics can disrupt normal intestinal flora, causing colonization of C difficile, but the strongest association seems to be with third- and fourth-generation cephalosporins, fluoroquinolones, carbapenems, and clindamycin.11 The risk for CDI occurs during antibiotic treatment, as well as up to 3 months after completion of antibiotic therapy.7 Exposure to multiple antibiotics and extended duration of antibacterial therapy can greatly increase the risk for CDI, so antimicrobial stewardship is key.11
Continue to: Continuing antibiotics while attempting...
Continuing antibiotics while attempting to treat CDI reduces the patient’s clinical response to CDI treatment, which can lead to recurrence.12 The Infectious Diseases Society of America (IDSA) guidelines include a strong recommendation to discontinue concurrent antibiotics as soon as possible in these scenarios.11
Acid-suppression therapy has also been associated with CDI. The mechanism is thought to be an interruption in the protection provided by stomach acid, and use over time may reduce the diversity of flora within the gut microbiome.13 The data demonstrating an association between acid-suppression therapy and CDI is conflicting, which may be a result of confounding factors such as the severity of CDI illness and diarrhea induced by use of proton pump inhibitors (PPIs).4 IDSA guidelines do not provide a recommendation regarding discontinuation of PPI therapy for the prevention of CDI, although inappropriate PPI therapy should always be discontinued.11
Advanced age is an important nonmodifiable risk factor for CDI. Older adults who live in long-term care facilities are at a higher risk for CDI, and these facilities have colonization rates as high as 50%.12
Community-associated risk. In an analysis of community-associated cases of CDI, 82% of patients reported some sort of health care exposure (ranging from physician office visit to surgery admission), 64% reported the receipt of antimicrobial therapy, and 31% reported the use of PPIs.14 Inflammatory bowel disease (IBD) may also put community dwellers at higher risk for CDI and its complications.15
CASES 1 & 2
Both CASE patients have risk factors for CDI. Ms. O (CASE 1) is likely at risk for CDI after completion of her recent course of clindamycin. Ms. Z (CASE 2) has several risk factors for recurrent CDI, including advanced age (≥ 65 years), residence in a long-term care facility, prior antibiotic exposure, and immunodeficiency because of chemotherapy/steroid use.
Continue to: Diagnosis
Diagnosis: Who and how to test
CDI should be both a clinical and laboratory-confirmed diagnosis. Patients should be tested for CDI if they have 3 or more episodes of unexplainable, new-onset unformed stools in 24 hours.11 Asymptomatic patients should not be tested to avoid unnecessary testing and treatment of those who are colonized but not infected.11 It is not recommended to routinely test patients who have taken laxatives within the previous 48 hours.11
There are several stool-based laboratory test options for the diagnosis of CDI (TABLE 211,12,16) but no definitive recommendation for all institutions.11 Many institutions have now implemented PCR testing for the diagnosis of CDI. However, while the benefits of this test include reduced need for repeat testing and possible identification of carriers, it’s estimated that reports of CDI increase more than 50% when an institution switches to PCR testing.1 Nonetheless, a one-step, highly sensitive test such as PCR may be used if strict criteria are implemented and followed.
The increase in positive PCR tests has prompted evaluation of using another test in addition to or in place of PCR. Multistep testing options include a glutamate dehydrogenase assay (GDH) with a toxin EIA, GDH with a toxin EIA and final decision via PCR, or PCR with toxin EIA.11 Use of a multistep diagnostic algorithm may increase overall specificity up to 100%, which may improve determination of asymptomatic colonization vs active infection.16 (Patients who have negative toxin results with positive PCR likely have colonization but not infection and often do not require treatment.) IDSA guidelines recommend that the stool toxin test should be part of a multistep algorithm for diagnosis, rather than PCR alone, if strict criteria are not implemented for stool test submission.11
There is no need to perform a test of cure after a patient has been treated for CDI, and no repeat testing should be performed within 7 days of the previous test.11 After successful treatment, patients will continue to shed spores and test positively via PCR for weeks to months.11 When patients have a positive PCR test, there are several important infection control efforts that institutions should consider; see “IDSA weighs in on measures to combat C difficile.”
SIDEBAR
IDSA weighs in on measures to combat C difficile
The spores produced by Clostridioides difficile can survive for 5 months or longer on dry surfaces because of resistance to heat, acid, antibiotics, and many cleaning products.38 Unfortunately, spores transmitted from health care workers and the environment are the most likely cause of infection spreading in health care institutions. To prevent transmission of C difficile infection (CDI) throughout institutions, appropriate infection control measures are necessary.
Clinical practice guidelines from the Infectious Diseases Society of America (IDSA) recommend that patients with CDI be isolated to a private room with a dedicated toilet. Health care staff should wear gloves and gowns when entering the room of, or taking care of, a patient with CDI. For patients who are suspected of having CDI, contact precautions should be implemented while awaiting test results. When the diagnosis is confirmed, contact precautions should remain in place for at least 48 hours after resolution of diarrhea but may be continued until discharge.11
Practicing good hand hygiene is essential, especially in institutions with high rates of CDI or if fecal contamination is likely.11 Hand hygiene with soap and water is preferred, due to evidence of a higher spore removal rate, but alcohol-based alternatives may be used if necessary.11 In institutions with high rates of CDI, terminal (post-discharge) cleaning of rooms with a sporicidal agent should be considered.11
Asymptomatic carriers are also a concern for transmission of CDI in institutional settings. Screening and isolating patients who are carriers may prevent transmission, and some institutions have implemented this process to reduce the risk for CDI that originates in a health care facility.39 The IDSA guidelines do not make a recommendation regarding screening or isolation of asymptomatic carriers, so the decision is institution specific.11 These guidelines also recommend that patients presenting with similar infectious organisms be housed in the same room, if needed, to avoid cross-contamination to others or additional surfaces.11
For pediatric patients, testing recommendations vary by age. Testing is not generally recommended for neonates or infants ≤ 2 years of age with diarrhea because of the prevalence of colonization with C difficile.11 For children older than 2 years, testing for CDI is only recommended in the setting of prolonged or worsening diarrhea and if the patient has risk factors such as IBD, immunocompromised state, health care exposure, or recent antibiotic use.11 In addition, testing in this population should only be considered once other infectious and noninfectious causes of diarrhea have been excluded.11
Continue to: First-line treatment? Drug of choice has changed
First-line treatment? Drug of choice has changed
In 2018, the IDSA published new treatment guidelines that provide important updates from the 2010 guidelines.11 Chief among these was the elimination of metronidazole as a first-line therapy. Vancomycin or fidaxomicin are now recommended as first-line treatment options because of superior eradication of C difficile when compared with metronidazole.11 In the opinion of the authors, vancomycin should be considered the drug of choice because of cost. (See “The case for vancomycin.”)
SIDEBAR
The case for vancomycin
The majority of studies conducted prior to publication of the 2010 Infectious Diseases Society of America guidelines described numerically worse eradication rates of Clostridioides difficile infection (CDI) with metronidazole compared with vancomycin for all severities of infection, but statistical significance was not achieved. These studies also showed a nonsignificant increase in CDI recurrence with metronidazole.17,40,41
A 2005 systematic review demonstrated increased treatment failure rates with metronidazole.42 The rates of metronidazole discontinuation and transition to alternative options more than doubled in 2003-2004, to 25.7% of patients compared with 9.6% in earlier years.42 Metronidazole efficacy was further questioned in a prospective observational study conducted in 2005, in which only 50% of patients were cured after an initial course of treatment, while 28% had recurrence within 90 days.43
Vancomycin was found to be the superior treatment option to metronidazole and tolevamer in a 2014 randomized controlled trial.18 This study also demonstrated that vancomycin was the superior therapy when comparing treatment-naïve vs experienced patients and severity of CDI.18 A 2017 retrospective cohort study demonstrated decreased 30-day all-cause mortality for patients taking vancomycin vs metronidazole (adjusted relative risk = 0.86; 95% confidence interval, 0.74-0.98), although it should be noted that this difference was driven by those with severe CDI, and there was no statistically significant difference in mortality for patients with mild-to-moderate CDI.44
The results of these studies led to the recommendation of vancomycin over metronidazole as first-line pharmacotherapy for CDI in practice, despite the historical perspective that overutilization of oral vancomycin could potentially increase rates of vancomycinresistant Enterococcus.11
Metronidazole should only be used in the treatment of CDI as a lastresort medication because of cost or insurance coverage. Although the price of oral vancomycin is higher, favorable patient outcomes are substantially greater, and recent analyses have shown that vancomycin is actually more cost-effective than metronidazole as a result.24 Adverse effects for metronidazole include neurotoxicity, gastrointestinal discomfort, and disulfiram-like reaction.
Vancomycin does not harbor as many adverse effects because of extremely low systemic absorption when taken orally, but patients may experience gastrointestinal discomfort.45 While systemic exposure with oral administration of vancomycin is very low (< 1%), there have been case reports of nephrotoxicity and “red man syndrome” that are more typically seen with intravenous vancomycin.44
Given the low rate of systemic exposure, routine monitoring of renal function and serum drug levels is not usually necessary during oral vancomycin therapy. However, it may be appropriate to monitor renal function and serum levels of vancomycin in patients who have renal failure, have altered intestinal integrity, are age ≥ 65 years, or are receiving high doses of vancomycin.46
10-day vs 14-day treatment of CDI. Most studies for the treatment of CDI have used a 10-day regimen rather than increasing the duration to a 14-day regimen, and nearly all studies conducted have displayed high rates of symptom resolution at the end of 10 days of treatment.17,18 Thus, treatment duration beyond 10 days should only be considered for patients who continue to have symptoms or complications with CDI on Day 10 of treatment.
First recurrence. Metronidazole is no longer the recommended treatment for first recurrence of CDI treated initially with metronidazole; instead, a 10-day course of vancomycin should be used.11 For recurrent cases in patients initially treated with vancomycin, a tapered and pulsed regimen of vancomycin is recommended11:
- vancomycin PO 125 mg four times daily for 10 to 14 days followed by
- vancomycin PO 125 mg twice daily for 7 days, then
- vancomycin PO 125 mg once daily for 7 days, then
- vancomycin PO 125 mg every 2 to 3 days for 2 to 8 weeks.
Pediatric patients. The IDSA guidelines recommend use of metronidazole or vancomycin to treat an initial case or first recurrence of mild-to-moderate CDI in this population.11 Due to a lack of quality evidence, the drug of choice for initial treatment is inconclusive, so patient-specific factors and cost should be considered when choosing an agent.11 If not cost prohibitive, vancomycin should be the drug of choice for most cases of pediatric CDI, and for severe cases or multiple recurrences of CDI, vancomycin is clearly the drug of choice.
Recommended agents: A closer look
Oral vancomycin products. Vancocin, a capsule, and Firvanq, an oral solution, are 2 vancomycin products currently on the market for CDI. Although the capsules are a readily available treatment option, the cost of the full course of treatment can be a barrier for patients without insurance, or with high copays or deductibles (brand name, $4000; generic, $1252).19
Continue to: Historically, in an effort to keep costs down...
Historically, in an effort to keep costs down, an oral solution was often inexpensively compounded at hospitals or pharmacies.20
Fidaxomicin, an oral macrocyclic antibiotic with minimal systemic absorption, was first approved by the US Food and Drug Administration (FDA) for CDI in 2011.21 The IDSA guidelines recommend fidaxomicin for initial, and recurrent, cases of CDI as an alternative to vancomycin.11 This recommendation is based on 2 randomized double-blind trials comparing fidaxomicin to standard-dose oral vancomycin for initial or recurrent CDI.21,22
Pooled data from these 2 similar studies found that fidaxomicin was noninferior (10% noninferiority margin) to vancomycin for the primary outcome of clinical cure.23 Fidaxomicin was shown to be superior to vancomycin regarding rate of CDI recurrence (relative risk [RR] = 0.61; 95% confidence interval [CI], 0.43-0.87). These results were similar regardless of whether the CDI was an initial or recurrent case.23
Given the lack of systemic absorption, fidaxomicin is generally very well tolerated. The largest downside to fidaxomicin is its cost, which can be nearly $5000 for a standard 10-day course (vs as little as $165 for oral vancomycin).19 As a result, oral vancomycin solution is likely the most cost-effective therapy for initial cases of CDI.24 In patients with poor medication adherence, fidaxomicin offers the advantage of less-frequent dosing (twice daily vs 4 times daily with vancomycin).
For cases of recurrent CDI, when treatment failure occurred with vancomycin, fidaxomicin should be considered as an efficacious alternative. If fidaxomicin is used, it is advisable to verify coverage with the patient’s insurance plan, since prior authorization is frequently required.
Continue to: When meds fail, consider a fecal microbiota transplant
When meds fail, consider a fecal microbiota transplant
Another important change in the IDSA guidelines for CDI management is the strong recommendation for fecal microbiota transplantation (FMT) in patients with multiple recurrences of CDI for whom appropriate antibiotic treatment courses have failed.11,25 The goal of FMT is to “normalize” an abnormal gut microbiome by transplanting donor stool into a recipient.26
FMT has been shown to be highly effective in 5 randomized clinical trials conducted since 2013, with CDI cure rates between 85% and 94%.11 This rate of cure is particularly impressive given that the studies only included patients with refractory CDI.
Patients with recurrent CDI who may be candidates for FMT should be referred to a center or specialist with experience in FMT. These transplants can be expensive because of the screening process involved in obtaining donor samples. (Historically, a single FMT has cost $3000-$5000, and it is seldom covered by insurance.27) The emergence of universal stool banks offers a streamlined solution to this process.26
Fresh or frozen stool is considered equally effective in treating refractory CDI.26 Oral capsule and freeze-dried stool formulations have been studied, but their use is considered investigational at this time.26
Delivery via colonoscopy to the right colon is the preferred route of infusion; however, delivery via enema or nasogastric, nasojejunal, or nasoduodenal infusion can be considered as well.26
Continue to: In preparing for stool transplantation...
In preparing for stool transplantation, patients should be treated with standard doses of oral vancomycin or fidaxomicin for 3 days before the procedure to suppress intestinal C difficile, and the last dose of antibiotics should be given 12 to 48 hours before the procedure.26 Bowel lavage with polyethylene glycol is recommended, regardless of whether stool is delivered via colonoscopy or upper GI route.
Short-term adverse events associated with FMT appear to be minimal; data is lacking for long-term safety outcomes.28 While only recommended currently for cases of recurrent CDI, there is promising data emerging for use of FMT for severe cases, even without recurrence.29
The role of probiotics remains unclear
Probiotics have been explored in numerous trials to determine if they are effective in preventing CDI in patients who have been prescribed antibiotics.11 While no randomized trials have conclusively shown benefit, several meta-analyses have shown that the use of probiotics may result in a 60% to 65% relative risk reduction in CDI incidence.30,31
One proviso to these meta-analyses is that the incorporated studies have typically included patients at very high risk for CDI, and subanalyses have only found a reduction in CDI incidence when patients are at a very high baseline risk. In addition, there are many differences in probiotic types, formulations, treatment durations, and follow-up. As a result, the IDSA guidelines state that there is “insufficient data at this time” to recommend routine administration of probiotics for either primary or secondary CDI prophylaxis.11
Due to insufficient high-quality data, the IDSA guidelines do not provide a recommendation regarding use as an adjunct treatment option for acute CDI.11 Probiotics should not be routinely used to prevent CDI; however, they may provide benefit if reserved for patients at the highest risk for CDI (eg, history of CDI, prolonged use of broad-spectrum antibiotics, high local incidence).
Continue to: What about surgical intervention?
What about surgical intervention?
In severe cases of CDI, surgery may be necessary and can reduce mortality.32 The surgical procedure with the strongest recommendation in the IDSA guidelines is the subtotal colectomy, though the diverting loop ileostomy is an alternative option.11 Patients who may benefit from surgery include those with a WBC count ≥ 25,000; lactate > 5 mmol/L11; altered mental status; megacolon; perforation of the colon; acute abdomen on physical examination; or septic shock due to CDI.33 Although surgery can be beneficial, the mortality rate remains high for those with CDI who undergo colectomy.33
Reserve bezlotoxumab for prevention of recurrence
Bezlotoxumab, a human monoclonal immunoglobulin GI/kappa antibody, was approved by the FDA in 2016 for the prevention of recurrent CDI. Its mechanism of action is to bind and neutralize C difficile toxin B. It was approved as a single infusion for adults who are receiving active antibiotic therapy for CDI and are considered to be at high risk for recurrence.34
This approval was based on 2 trials of more than 2500 patients, in which participants received bezlotoxumab or placebo while receiving treatment for primary or recurrent CDI. The primary outcome of these studies was recurrent infection within 12 weeks after infusion, which was significantly lower for bezlotoxumab in both studies: 17% vs 28% (P < 0.001) in one trial and 16% vs 26% (P < 0.001) in the other trial.35
Bezlotoxumab should only be used as an adjunct to prevent recurrence.32 There is no recommendation for or against bezlotoxumab in the IDSA guidelines because of the recent date of the drug’s approval. Its frequency of use will likely depend on the number of patients who meet criteria as high risk for recurrence and its estimated cost of $4560 per dose.34,36
CASES
CASE 1: In light of Ms. O’s recent completion of a course of clindamycin and unremarkable lab work, she should be treated for mild-to-moderate CDI. She has no comorbid conditions to warrant fidaxomicin, and thus vancomycin (capsules or oral solution) would be the best treatment option. Ms. O is started on vancomycin PO 125 mg qid for 10 days. She is also advised to discontinue loperamide as soon as possible, based on poor outcomes data seen with the use of antimotility agents in CDI.37
Continue to: CASE 2
CASE 2: Ms. Z has several risk factors for recurrent CDI and has an elevated WBC count and SCr level (WBC ≥ 15,000 and SCr > 1.5 mg/dL). Thus, she is classified as having severe, recurrent CDI. Oral levofloxacin and metronidazole should be discontinued, because they increase the risk for treatment failure and development of more virulent CDI strains, such as BI/NAP1/027. Since Ms. Z used metronidazole for treatment of her initial CDI, vancomycin or fidaxomicin should be used at this time. Either vancomycin PO 125 mg qid for 10 days or fidaxomicin 200 mg bid for 10 days would be an appropriate regimen; however, because of cost and unknown insurance coverage, vancomycin is the most appropriate regimen.
CORRESPONDENCE
Jeremy Vandiver, PharmD, BCPS, University of Wyoming School of Pharmacy, Saint Joseph Family Medicine Residency, 1000 E. University Avenue, Dept 3375, Laramie, WY 82071; [email protected]
1. Polage CR, Gyorke CE, Kennedy MA, et al. Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med. 2015;175:1792-1801.
2. Reveles KR, Lee GC, Boyd NK, et al. The rise in Clostridium difficile infection incidence among hospitalized adults in the United States: 2001-2010. Am J Infect Control. 2014;42:1028-1032.
3. Dubberke ER, Olsen MA. Burden of Clostridium difficile on the healthcare system. Clin Infect Dis. 2012;55(suppl 2):S88-S92.
4. Tariq R, Singh S, Gupta A, et al. Association of gastric acid suppression with recurrent Clostridium difficile infection: a systematic review and meta-analysis. JAMA Intern Med. 2017;177:784-791.
5. Kachrimanidou M, Malisiovas N. Clostridium difficile infection: a comprehensive review. Crit Rev Microbiol. 2011;37:178-187.
6. O’Connor JR, Johnson S, Gerding DN. Clostridium difficile infection caused by the epidemic BI/NAP1/027 strain. Gastroenterology. 2009;136:1913-1924.
7. Kelly CP. A 76-year-old man with recurrent Clostridium difficile-associated diarrhea: review of C difficile infection. JAMA. 2009;301:954-962.
8. Cornely OA, Miller MA, Louie TJ, et al. Treatment of first recurrence of Clostridium difficile infection: fidaxomicin versus vancomycin. Clin Infect Dis. 2012;55(suppl 2):S154-S161.
9. Napolitano LM, Edmiston CE Jr. Clostridium difficile disease: diagnosis, pathogenesis, and treatment update. Surgery 2017;162:325-348.
10. Deshpande A, Pasupuleti V, Thota P, et al. Risk factors for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol. 2015;36:452-460.
11. McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66:e1-e48.
12. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108:478-498; quiz 499.
13. Seto CT, Jeraldo P, Orenstein R, et al. Prolonged use of a proton pump inhibitor reduces microbial diversity: implications for Clostridium difficile susceptibility. Microbiome. 2014;2:42.
14. Chitnis AS, Holzbauer SM, Belflower RM, et al. Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. JAMA Intern Med. 2013;173:1359-1367.
15. Negrón ME, Rezaie A, Barkema HW, et al. Ulcerative colitis patients with Clostridium difficile are at increased risk of death, colectomy, and postoperative complications: a population-based inception cohort study. Am J Gastroenterol. 2016;111:691-704.
16. Bagdasarian N, Rao K, Malani PN. Diagnosis and treatment of Clostridium difficile in adults: a systematic review. JAMA. 2015;313:398-408.
17. Zar FA, Bakkanagari SR, Moorthi KM, et al. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45:302-307.
18. Johnson S, Louie TJ, Gerding DN, et al. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014;59:345-354.
19. Vancomycin: product details. Redbook Online. www.micromedexsolutions.com. Published 2018. Accessed June 13, 2020.
20. Mergenhagen KA, Wojciechowski AL, Paladino JA. A review of the economics of treating Clostridium difficile infection. Pharmacoeconomics. 2014;32:639-650.
21. Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422-431.
22. Cornely OA, Crook DW, Esposito R, et al. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis. 2012;12:281-289.
23. Crook DW, Walker AS, Kean Y, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials. Clin Infect Dis. 2012;55 suppl 2:S93-103.
24. Ford DC, Schroeder MC, Ince D, et al. Cost-effectiveness analysis of initial treatment strategies for mild-to-moderate Clostridium difficile infection in hospitalized patients. Am J Health Syst Pharm. 2018;75:1110-1121.
25. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31:431-455.
26. Panchal P, Budree S, Scheeler A, et al. Scaling safe access to fecal microbiota transplantation: past, present, and future. Curr Gastroenterol Rep. 2018;20:14.
27. Arbel LT, Hsu E, McNally K. Cost-effectiveness of fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection: a literature review. Cureus. 2017;9:e1599.
28. Cammarota G, Ianiro G, Tilg H, et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017;66:569-580.
29. Hocquart M, Lagier JC, Cassir N, et al. Early fecal microbiota transplantation improves survival in severe Clostridium difficile infections. Clin Infect Dis. 2018;66:645-650.
30. Goldenberg JZ, Yap C, Lytvyn L, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017;12:CD006095.
31. Johnston BC, Lytvyn L, Lo CK, et al. Microbial preparations (probiotics) for the prevention of Clostridium difficile infection in adults and children: an individual patient data meta-analysis of 6,851 participants. Infect Control Hosp Epidemiol. 2018:1-11.
32. Stewart DB, Hollenbeak CS, Wilson MZ. Is colectomy for fulminant Clostridium difficile colitis life saving? A systematic review. Colorectal Dis. 2013;15:798-804.
33. Julien M, Wild JL, Blansfield J, et al. Severe complicated Clostridium difficile infection: can the UPMC proposed scoring system predict the need for surgery? J Trauma Acute Care Surg. 2016;81:221-228.
34. Merck & Co, Inc. Sharp M. ZinplavaTM (bezlotoxumab [package insert] US Food and Drug Administration Web site. www.accessdata.fda.gov/drugsatfda_docs/label/2016/761046s000lbl.pdf. Revised October 2016. Accessed May 29, 2020.
35. Wilcox MH, Gerding DN, Poxton IR, et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376:305-317.
36. Chahine EB, Cho JC, Worley MV. Bezlotoxumab for the Prevention of Clostridium difficile recurrence. Consult Pharm. 2018;33:89-97.
37. Koo HL, Koo DC, Musher DM, et al. Antimotility agents for the treatment of Clostridium difficile diarrhea and colitis. Clin Infect Dis. 2009;48:598-605.
38. Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol. 2009;7:526-536.
39. Longtin Y, Paquet-Bolduc B, Gilca R, et al. Effect of detecting and isolating Clostridium difficile carriers at hospital admission on the incidence of C difficile infections: a quasi-experimental controlled study. JAMA Intern Med. 2016;176:796-804.
40. Teasley DG, Gerding DN, Olson MM, et al. Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet. 1983;2:1043-1046.
41. Wenisch C, Parschalk B, Hasenhündl M, et al. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis. 1996;22:813-818.
42. Pepin J, Alary ME, Valiquette L, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis. 2005;40:1591-1597.
43. Musher DM, Aslam S, Logan N, et al. Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis. 2005;40:1586-1590.
44. Stevens VW, Nelson RE, Schwab-Daugherty EM, et al. Comparative effectiveness of vancomycin and metronidazole for the prevention of recurrence and death in patients with Clostridium difficile infection. JAMA Intern Med. 2017;177:546-553.
45. CutisPharma. FirvanqTM (vancomycin hydrochloride) for oral solution [package insert]. US Food and Drug Administration Web site. www.accessdata.fda.gov/drugsatfda_docs/label/2018/208910s000lbl.pdf. Revised January 2018. Accessed May 29, 2020.
46.
1. Polage CR, Gyorke CE, Kennedy MA, et al. Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med. 2015;175:1792-1801.
2. Reveles KR, Lee GC, Boyd NK, et al. The rise in Clostridium difficile infection incidence among hospitalized adults in the United States: 2001-2010. Am J Infect Control. 2014;42:1028-1032.
3. Dubberke ER, Olsen MA. Burden of Clostridium difficile on the healthcare system. Clin Infect Dis. 2012;55(suppl 2):S88-S92.
4. Tariq R, Singh S, Gupta A, et al. Association of gastric acid suppression with recurrent Clostridium difficile infection: a systematic review and meta-analysis. JAMA Intern Med. 2017;177:784-791.
5. Kachrimanidou M, Malisiovas N. Clostridium difficile infection: a comprehensive review. Crit Rev Microbiol. 2011;37:178-187.
6. O’Connor JR, Johnson S, Gerding DN. Clostridium difficile infection caused by the epidemic BI/NAP1/027 strain. Gastroenterology. 2009;136:1913-1924.
7. Kelly CP. A 76-year-old man with recurrent Clostridium difficile-associated diarrhea: review of C difficile infection. JAMA. 2009;301:954-962.
8. Cornely OA, Miller MA, Louie TJ, et al. Treatment of first recurrence of Clostridium difficile infection: fidaxomicin versus vancomycin. Clin Infect Dis. 2012;55(suppl 2):S154-S161.
9. Napolitano LM, Edmiston CE Jr. Clostridium difficile disease: diagnosis, pathogenesis, and treatment update. Surgery 2017;162:325-348.
10. Deshpande A, Pasupuleti V, Thota P, et al. Risk factors for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol. 2015;36:452-460.
11. McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66:e1-e48.
12. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108:478-498; quiz 499.
13. Seto CT, Jeraldo P, Orenstein R, et al. Prolonged use of a proton pump inhibitor reduces microbial diversity: implications for Clostridium difficile susceptibility. Microbiome. 2014;2:42.
14. Chitnis AS, Holzbauer SM, Belflower RM, et al. Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. JAMA Intern Med. 2013;173:1359-1367.
15. Negrón ME, Rezaie A, Barkema HW, et al. Ulcerative colitis patients with Clostridium difficile are at increased risk of death, colectomy, and postoperative complications: a population-based inception cohort study. Am J Gastroenterol. 2016;111:691-704.
16. Bagdasarian N, Rao K, Malani PN. Diagnosis and treatment of Clostridium difficile in adults: a systematic review. JAMA. 2015;313:398-408.
17. Zar FA, Bakkanagari SR, Moorthi KM, et al. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45:302-307.
18. Johnson S, Louie TJ, Gerding DN, et al. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014;59:345-354.
19. Vancomycin: product details. Redbook Online. www.micromedexsolutions.com. Published 2018. Accessed June 13, 2020.
20. Mergenhagen KA, Wojciechowski AL, Paladino JA. A review of the economics of treating Clostridium difficile infection. Pharmacoeconomics. 2014;32:639-650.
21. Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422-431.
22. Cornely OA, Crook DW, Esposito R, et al. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis. 2012;12:281-289.
23. Crook DW, Walker AS, Kean Y, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials. Clin Infect Dis. 2012;55 suppl 2:S93-103.
24. Ford DC, Schroeder MC, Ince D, et al. Cost-effectiveness analysis of initial treatment strategies for mild-to-moderate Clostridium difficile infection in hospitalized patients. Am J Health Syst Pharm. 2018;75:1110-1121.
25. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31:431-455.
26. Panchal P, Budree S, Scheeler A, et al. Scaling safe access to fecal microbiota transplantation: past, present, and future. Curr Gastroenterol Rep. 2018;20:14.
27. Arbel LT, Hsu E, McNally K. Cost-effectiveness of fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection: a literature review. Cureus. 2017;9:e1599.
28. Cammarota G, Ianiro G, Tilg H, et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017;66:569-580.
29. Hocquart M, Lagier JC, Cassir N, et al. Early fecal microbiota transplantation improves survival in severe Clostridium difficile infections. Clin Infect Dis. 2018;66:645-650.
30. Goldenberg JZ, Yap C, Lytvyn L, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017;12:CD006095.
31. Johnston BC, Lytvyn L, Lo CK, et al. Microbial preparations (probiotics) for the prevention of Clostridium difficile infection in adults and children: an individual patient data meta-analysis of 6,851 participants. Infect Control Hosp Epidemiol. 2018:1-11.
32. Stewart DB, Hollenbeak CS, Wilson MZ. Is colectomy for fulminant Clostridium difficile colitis life saving? A systematic review. Colorectal Dis. 2013;15:798-804.
33. Julien M, Wild JL, Blansfield J, et al. Severe complicated Clostridium difficile infection: can the UPMC proposed scoring system predict the need for surgery? J Trauma Acute Care Surg. 2016;81:221-228.
34. Merck & Co, Inc. Sharp M. ZinplavaTM (bezlotoxumab [package insert] US Food and Drug Administration Web site. www.accessdata.fda.gov/drugsatfda_docs/label/2016/761046s000lbl.pdf. Revised October 2016. Accessed May 29, 2020.
35. Wilcox MH, Gerding DN, Poxton IR, et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376:305-317.
36. Chahine EB, Cho JC, Worley MV. Bezlotoxumab for the Prevention of Clostridium difficile recurrence. Consult Pharm. 2018;33:89-97.
37. Koo HL, Koo DC, Musher DM, et al. Antimotility agents for the treatment of Clostridium difficile diarrhea and colitis. Clin Infect Dis. 2009;48:598-605.
38. Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol. 2009;7:526-536.
39. Longtin Y, Paquet-Bolduc B, Gilca R, et al. Effect of detecting and isolating Clostridium difficile carriers at hospital admission on the incidence of C difficile infections: a quasi-experimental controlled study. JAMA Intern Med. 2016;176:796-804.
40. Teasley DG, Gerding DN, Olson MM, et al. Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet. 1983;2:1043-1046.
41. Wenisch C, Parschalk B, Hasenhündl M, et al. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis. 1996;22:813-818.
42. Pepin J, Alary ME, Valiquette L, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis. 2005;40:1591-1597.
43. Musher DM, Aslam S, Logan N, et al. Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis. 2005;40:1586-1590.
44. Stevens VW, Nelson RE, Schwab-Daugherty EM, et al. Comparative effectiveness of vancomycin and metronidazole for the prevention of recurrence and death in patients with Clostridium difficile infection. JAMA Intern Med. 2017;177:546-553.
45. CutisPharma. FirvanqTM (vancomycin hydrochloride) for oral solution [package insert]. US Food and Drug Administration Web site. www.accessdata.fda.gov/drugsatfda_docs/label/2018/208910s000lbl.pdf. Revised January 2018. Accessed May 29, 2020.
46.
PRACTICE RECOMMENDATIONS
› Keep in mind that previous exposure to antibiotics is the most important risk factor for initial and recurrent Clostridioides difficile infection (CDI). Thus, appropriate antimicrobial stewardship is key to prevention. C
› Begin with vancomycin or fidaxomicin (over metronidazole) for first-line treatment of CDI in adults. A
› Consider fecal microbiota transplantation in high-risk patients with recurrent CDI for whom antimicrobial therapy has failed. A
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
Simplifying the antibiotic selection process
Hospitalists are constantly battling infection.
James Soo Kim, MD, a hospitalist and assistant professor at Emory Healthcare in Atlanta, a presenter of the session “Antibiotics Made Ridiculously Simple” during HM20 Virtual, said that while he has given this talk at previous Society of Hospital Medicine Annual Conferences, the presentation has undergone significant changes over the years as the landscape of infectious disease treatment has shifted.
He hopes attendees of HM20 Virtual will appreciate the changes and encourages those who have attended his presentation in previous years to come see what is new, but admitted newcomers may think the presentation’s title is a bit of a misnomer.
“Despite the title of the talk, there really isn’t any way to make antibiotics ridiculously simple,” he said.
Dr. Kim, who is also an editorial board member for The Hospitalist, said the origin of “Antibiotics Made Ridiculously Simple” took place during his residency, where he had an interest in infectious disease. This interest carried over to his time in fellowship at the Keck School of Medicine of the University of Southern California – and was enough to become board certified in infectious disease by the American Board of Internal Medicine. Infectious disease continues to interest him now as an attending, he said, and since he joined Emory Healthcare in 2012, he has given a version of this presentation every year.
HM20 Virtual attendees will come away from the presentation with an idea of how to choose an antibiotic regimen, Dr. Kim said, including how to select an antibiotic when you’re worried about Pseudomonas, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus or other likely organisms. “There are a variety of drugs out there that have activity against our ‘usual suspects,’ ” he said.
Attendees will also learn to select antibiotic options that have empiric coverage during a shortage of piperacillin/tazobactam (Zosyn), vancomycin, or your preferred drug of choice for treating common infections. He will also review the latest drugs that have been released over the past few years so attendees can add them to their armamentarium.
“I won’t necessarily expect attendees to use everything I talk about, but if you have a patient on service that infectious disease started Vabomere on, you’ll at least have a general idea of what they were worried about,” Dr. Kim said.
One practice pearl he hopes attendees take away from his presentation: Allergies to beta-lactam antibiotics like penicillin (PCN) derivatives are not as common as most providers and patients believe, and not giving these antibiotics to patients can actually decrease the chance that the patient gets appropriate therapy while also increasing the cost of care.
“I hope that my talk changes practice by making people aware of how infrequent true clinically significant PCN cross-reactions are so that patients can get more cost-effective and medically effective therapy,” he said.Dr. Kim reports no relevant financial disclosures.
Antibiotics Made Ridiculously Simple Live Q&A: Tuesday, August 18, 3:30-4:30 p.m.
Hospitalists are constantly battling infection.
James Soo Kim, MD, a hospitalist and assistant professor at Emory Healthcare in Atlanta, a presenter of the session “Antibiotics Made Ridiculously Simple” during HM20 Virtual, said that while he has given this talk at previous Society of Hospital Medicine Annual Conferences, the presentation has undergone significant changes over the years as the landscape of infectious disease treatment has shifted.
He hopes attendees of HM20 Virtual will appreciate the changes and encourages those who have attended his presentation in previous years to come see what is new, but admitted newcomers may think the presentation’s title is a bit of a misnomer.
“Despite the title of the talk, there really isn’t any way to make antibiotics ridiculously simple,” he said.
Dr. Kim, who is also an editorial board member for The Hospitalist, said the origin of “Antibiotics Made Ridiculously Simple” took place during his residency, where he had an interest in infectious disease. This interest carried over to his time in fellowship at the Keck School of Medicine of the University of Southern California – and was enough to become board certified in infectious disease by the American Board of Internal Medicine. Infectious disease continues to interest him now as an attending, he said, and since he joined Emory Healthcare in 2012, he has given a version of this presentation every year.
HM20 Virtual attendees will come away from the presentation with an idea of how to choose an antibiotic regimen, Dr. Kim said, including how to select an antibiotic when you’re worried about Pseudomonas, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus or other likely organisms. “There are a variety of drugs out there that have activity against our ‘usual suspects,’ ” he said.
Attendees will also learn to select antibiotic options that have empiric coverage during a shortage of piperacillin/tazobactam (Zosyn), vancomycin, or your preferred drug of choice for treating common infections. He will also review the latest drugs that have been released over the past few years so attendees can add them to their armamentarium.
“I won’t necessarily expect attendees to use everything I talk about, but if you have a patient on service that infectious disease started Vabomere on, you’ll at least have a general idea of what they were worried about,” Dr. Kim said.
One practice pearl he hopes attendees take away from his presentation: Allergies to beta-lactam antibiotics like penicillin (PCN) derivatives are not as common as most providers and patients believe, and not giving these antibiotics to patients can actually decrease the chance that the patient gets appropriate therapy while also increasing the cost of care.
“I hope that my talk changes practice by making people aware of how infrequent true clinically significant PCN cross-reactions are so that patients can get more cost-effective and medically effective therapy,” he said.Dr. Kim reports no relevant financial disclosures.
Antibiotics Made Ridiculously Simple Live Q&A: Tuesday, August 18, 3:30-4:30 p.m.
Hospitalists are constantly battling infection.
James Soo Kim, MD, a hospitalist and assistant professor at Emory Healthcare in Atlanta, a presenter of the session “Antibiotics Made Ridiculously Simple” during HM20 Virtual, said that while he has given this talk at previous Society of Hospital Medicine Annual Conferences, the presentation has undergone significant changes over the years as the landscape of infectious disease treatment has shifted.
He hopes attendees of HM20 Virtual will appreciate the changes and encourages those who have attended his presentation in previous years to come see what is new, but admitted newcomers may think the presentation’s title is a bit of a misnomer.
“Despite the title of the talk, there really isn’t any way to make antibiotics ridiculously simple,” he said.
Dr. Kim, who is also an editorial board member for The Hospitalist, said the origin of “Antibiotics Made Ridiculously Simple” took place during his residency, where he had an interest in infectious disease. This interest carried over to his time in fellowship at the Keck School of Medicine of the University of Southern California – and was enough to become board certified in infectious disease by the American Board of Internal Medicine. Infectious disease continues to interest him now as an attending, he said, and since he joined Emory Healthcare in 2012, he has given a version of this presentation every year.
HM20 Virtual attendees will come away from the presentation with an idea of how to choose an antibiotic regimen, Dr. Kim said, including how to select an antibiotic when you’re worried about Pseudomonas, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus or other likely organisms. “There are a variety of drugs out there that have activity against our ‘usual suspects,’ ” he said.
Attendees will also learn to select antibiotic options that have empiric coverage during a shortage of piperacillin/tazobactam (Zosyn), vancomycin, or your preferred drug of choice for treating common infections. He will also review the latest drugs that have been released over the past few years so attendees can add them to their armamentarium.
“I won’t necessarily expect attendees to use everything I talk about, but if you have a patient on service that infectious disease started Vabomere on, you’ll at least have a general idea of what they were worried about,” Dr. Kim said.
One practice pearl he hopes attendees take away from his presentation: Allergies to beta-lactam antibiotics like penicillin (PCN) derivatives are not as common as most providers and patients believe, and not giving these antibiotics to patients can actually decrease the chance that the patient gets appropriate therapy while also increasing the cost of care.
“I hope that my talk changes practice by making people aware of how infrequent true clinically significant PCN cross-reactions are so that patients can get more cost-effective and medically effective therapy,” he said.Dr. Kim reports no relevant financial disclosures.
Antibiotics Made Ridiculously Simple Live Q&A: Tuesday, August 18, 3:30-4:30 p.m.
Get updated: Latest ATS/ISDA guidelines for pneumonia
according to Joanna M. Bonsall, MD, PhD, SFHM, chief of hospital medicine at Grady Memorial Hospital and associate professor of medicine at Emory University, both in Atlanta.
Last year, the American Thoracic Society and the Infectious Diseases Society of America updated their clinical guidelines on community-acquired pneumonia (CAP) for the first time since 2007. The guidelines were published in the Oct. 1, 2019 issue of the American Journal of Respiratory and Critical Care Medicine.
CAP is one of the most common reasons for hospitalization in the United States, and it is estimated that CAP comprises over 4.5 million outpatient and ED visits each year, according to the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey in 2009-2010. It is also the most common cause of death from infection disease, according to the Centers for Disease Control and Prevention.
Dr. Bonsall will present “Updates in Pneumonia” at HM20 Virtual, the virtual annual meeting of the Society of Hospital Medicine; a live question-and-answer session will be held online Aug. 20. In her session, Dr. Bonsall said she plans to cover the new ATS/IDSA guidelines for CAP, which will include what initial testing to order, which empiric antibiotics to use, and how to manage patients at risk for resistant organisms, formerly known as health care–associated pneumonia (HCAP). Dr. Bonsall also will outline the evidence for use of steroids, especially in cases of severe pneumonia, and review the 2016 ATS/IDSA guidelines for hospital-acquired pneumonia with a focus on antibiotic selection.
One major change for 2019: The ATS/IDSA CAP guideline authors issued a strong recommendation to abandon use of the term HCAP as a “distinct clinical entity” when considering antibiotics for patients with CAP. In addition, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa should only be empirically covered in patients with CAP if they present with locally validated risk factors for either pathogen, according to the guidelines.
“Order pretreatment testing based on severity of illness as well as risk factors for drug-resistant pathogens,” Dr. Bonsall said. Hospitalists also should avoid using procalcitonin levels as a benchmark for whether a patient should be started on antibiotics. Once the recommended antibiotic treatment has been initiated, attendees should use culture results to narrow down the possibilities, especially in cases of drug-resistant pathogens.
The ATS/IDSA guidelines also state that corticosteroids should not be routinely used for patients with nonsevere CAP, but attendees should also be aware of the limitations and interpretations of the evidence, Dr. Bonsall said. Avoiding routine corticosteroid use in patients with severe CAP or in patients with severe influenza pneumonia carries a conditional recommendation with a moderate and low quality of evidence, respectively. In general, cases of CAP should be treated for no more than 5 days, or 3 days of treatment after the patient becomes clinically stable.
Attendees at HM20 Virtual should walk away from the session knowing what testing is necessary and what testing is unnecessary, and how to reduce antibiotic exposure for both broad spectrum use and duration. “At the end of the session, you should feel comfortable using both the CAP and HAP guidelines,” Dr. Bonsall said.
Dr. Bonsall reported no relevant financial disclosures.
Updates in Pneumonia
Live Q&A: Thursday, Aug. 20, 2:15 p.m to 3:15 p.m.
according to Joanna M. Bonsall, MD, PhD, SFHM, chief of hospital medicine at Grady Memorial Hospital and associate professor of medicine at Emory University, both in Atlanta.
Last year, the American Thoracic Society and the Infectious Diseases Society of America updated their clinical guidelines on community-acquired pneumonia (CAP) for the first time since 2007. The guidelines were published in the Oct. 1, 2019 issue of the American Journal of Respiratory and Critical Care Medicine.
CAP is one of the most common reasons for hospitalization in the United States, and it is estimated that CAP comprises over 4.5 million outpatient and ED visits each year, according to the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey in 2009-2010. It is also the most common cause of death from infection disease, according to the Centers for Disease Control and Prevention.
Dr. Bonsall will present “Updates in Pneumonia” at HM20 Virtual, the virtual annual meeting of the Society of Hospital Medicine; a live question-and-answer session will be held online Aug. 20. In her session, Dr. Bonsall said she plans to cover the new ATS/IDSA guidelines for CAP, which will include what initial testing to order, which empiric antibiotics to use, and how to manage patients at risk for resistant organisms, formerly known as health care–associated pneumonia (HCAP). Dr. Bonsall also will outline the evidence for use of steroids, especially in cases of severe pneumonia, and review the 2016 ATS/IDSA guidelines for hospital-acquired pneumonia with a focus on antibiotic selection.
One major change for 2019: The ATS/IDSA CAP guideline authors issued a strong recommendation to abandon use of the term HCAP as a “distinct clinical entity” when considering antibiotics for patients with CAP. In addition, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa should only be empirically covered in patients with CAP if they present with locally validated risk factors for either pathogen, according to the guidelines.
“Order pretreatment testing based on severity of illness as well as risk factors for drug-resistant pathogens,” Dr. Bonsall said. Hospitalists also should avoid using procalcitonin levels as a benchmark for whether a patient should be started on antibiotics. Once the recommended antibiotic treatment has been initiated, attendees should use culture results to narrow down the possibilities, especially in cases of drug-resistant pathogens.
The ATS/IDSA guidelines also state that corticosteroids should not be routinely used for patients with nonsevere CAP, but attendees should also be aware of the limitations and interpretations of the evidence, Dr. Bonsall said. Avoiding routine corticosteroid use in patients with severe CAP or in patients with severe influenza pneumonia carries a conditional recommendation with a moderate and low quality of evidence, respectively. In general, cases of CAP should be treated for no more than 5 days, or 3 days of treatment after the patient becomes clinically stable.
Attendees at HM20 Virtual should walk away from the session knowing what testing is necessary and what testing is unnecessary, and how to reduce antibiotic exposure for both broad spectrum use and duration. “At the end of the session, you should feel comfortable using both the CAP and HAP guidelines,” Dr. Bonsall said.
Dr. Bonsall reported no relevant financial disclosures.
Updates in Pneumonia
Live Q&A: Thursday, Aug. 20, 2:15 p.m to 3:15 p.m.
according to Joanna M. Bonsall, MD, PhD, SFHM, chief of hospital medicine at Grady Memorial Hospital and associate professor of medicine at Emory University, both in Atlanta.
Last year, the American Thoracic Society and the Infectious Diseases Society of America updated their clinical guidelines on community-acquired pneumonia (CAP) for the first time since 2007. The guidelines were published in the Oct. 1, 2019 issue of the American Journal of Respiratory and Critical Care Medicine.
CAP is one of the most common reasons for hospitalization in the United States, and it is estimated that CAP comprises over 4.5 million outpatient and ED visits each year, according to the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey in 2009-2010. It is also the most common cause of death from infection disease, according to the Centers for Disease Control and Prevention.
Dr. Bonsall will present “Updates in Pneumonia” at HM20 Virtual, the virtual annual meeting of the Society of Hospital Medicine; a live question-and-answer session will be held online Aug. 20. In her session, Dr. Bonsall said she plans to cover the new ATS/IDSA guidelines for CAP, which will include what initial testing to order, which empiric antibiotics to use, and how to manage patients at risk for resistant organisms, formerly known as health care–associated pneumonia (HCAP). Dr. Bonsall also will outline the evidence for use of steroids, especially in cases of severe pneumonia, and review the 2016 ATS/IDSA guidelines for hospital-acquired pneumonia with a focus on antibiotic selection.
One major change for 2019: The ATS/IDSA CAP guideline authors issued a strong recommendation to abandon use of the term HCAP as a “distinct clinical entity” when considering antibiotics for patients with CAP. In addition, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa should only be empirically covered in patients with CAP if they present with locally validated risk factors for either pathogen, according to the guidelines.
“Order pretreatment testing based on severity of illness as well as risk factors for drug-resistant pathogens,” Dr. Bonsall said. Hospitalists also should avoid using procalcitonin levels as a benchmark for whether a patient should be started on antibiotics. Once the recommended antibiotic treatment has been initiated, attendees should use culture results to narrow down the possibilities, especially in cases of drug-resistant pathogens.
The ATS/IDSA guidelines also state that corticosteroids should not be routinely used for patients with nonsevere CAP, but attendees should also be aware of the limitations and interpretations of the evidence, Dr. Bonsall said. Avoiding routine corticosteroid use in patients with severe CAP or in patients with severe influenza pneumonia carries a conditional recommendation with a moderate and low quality of evidence, respectively. In general, cases of CAP should be treated for no more than 5 days, or 3 days of treatment after the patient becomes clinically stable.
Attendees at HM20 Virtual should walk away from the session knowing what testing is necessary and what testing is unnecessary, and how to reduce antibiotic exposure for both broad spectrum use and duration. “At the end of the session, you should feel comfortable using both the CAP and HAP guidelines,” Dr. Bonsall said.
Dr. Bonsall reported no relevant financial disclosures.
Updates in Pneumonia
Live Q&A: Thursday, Aug. 20, 2:15 p.m to 3:15 p.m.
Sepsis: Vitamin C, thiamine, glucocorticoids remain controversial
Sepsis is the number one killer in U.S. hospitals. About one in three patient deaths in a hospital are attributable to sepsis, according to the Centers for Disease Control and Prevention, and it is the leading cause of readmission for U.S. hospitals as well.
Patricia Kritek MD, EdM, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, hopes to bring attendees up to speed on sepsis with her presentation, “Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis” at HM20 Virtual.
Each year, approximately 1.7 million American adults develop sepsis, and nearly 270,000 Americans will die from sepsis annually. Although sepsis disproportionately affects young children, older adults, patients with chronic diseases, and those with a weak immune system, the disease can affect anyone.
With that reputation, sepsis is on the forefront of hospitalists’ minds. Hospitalists are traditionally well versed in current sepsis guidelines, but time to treatment is paramount, and it can be difficult to stay up to date on the latest studies in the field.
The title of Dr. Kritek’s presentation hints at the theme: Hospitalists may have learned the systemic inflammatory response syndrome (SIRS) criteria for diagnosing sepsis, but the Sequential Organ Failure Assessment (SOFA) Score developed by the Third International Consensus Definitions for Sepsis and Septic Shock – previously known as the sepsis-related organ failure assessment score – has been the new method since 2016 to assess the clinical outcomes of patients with sepsis.
The quick SOFA score (qSOFA), developed by the Society of Critical Care and European Society of Intensive Care Medicine in 2016 guidelines, further helps hospitalists and other hospital physicians identify those patients at highest risk of mortality from sepsis outside an intensive care unit setting.
Dr. Kritek, who is a board-certified critical care medicine physician, has previously presented this talk at the Society for Hospital Medicine Annual Conference in the past. This year the presentation will include a number of studies that examine what role vitamin C, thiamine, and glucocorticoids have in treating patients with sepsis, she said. For example, it is thought that parenteral administration of vitamin C could raise plasma levels and reduce multiorgan failure. Thiamine could be useful in sepsis treatment because of its role in glucose metabolism and lactate production, while glucocorticoids could help improve the mortality rate of patients with sepsis.
While Dr. Kritek said she is not going to be advocating for the benefit of vitamin C and thiamine during the session, “this is an area of ongoing debate, and we will walk through the most recent data to try to make sense of it,” she said.
Dr. Kritek noted that the role of balanced crystalloids in resuscitation will be discussed versus when to use saline, as well as the potential of new vasopressors for the treatment of septic shock.
“Our goal will be to integrate the most recent literature into day-to-day practice,” Dr. Kritek said.Dr. Kritek reports no conflicts of interest.
“Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis”
Sepsis is the number one killer in U.S. hospitals. About one in three patient deaths in a hospital are attributable to sepsis, according to the Centers for Disease Control and Prevention, and it is the leading cause of readmission for U.S. hospitals as well.
Patricia Kritek MD, EdM, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, hopes to bring attendees up to speed on sepsis with her presentation, “Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis” at HM20 Virtual.
Each year, approximately 1.7 million American adults develop sepsis, and nearly 270,000 Americans will die from sepsis annually. Although sepsis disproportionately affects young children, older adults, patients with chronic diseases, and those with a weak immune system, the disease can affect anyone.
With that reputation, sepsis is on the forefront of hospitalists’ minds. Hospitalists are traditionally well versed in current sepsis guidelines, but time to treatment is paramount, and it can be difficult to stay up to date on the latest studies in the field.
The title of Dr. Kritek’s presentation hints at the theme: Hospitalists may have learned the systemic inflammatory response syndrome (SIRS) criteria for diagnosing sepsis, but the Sequential Organ Failure Assessment (SOFA) Score developed by the Third International Consensus Definitions for Sepsis and Septic Shock – previously known as the sepsis-related organ failure assessment score – has been the new method since 2016 to assess the clinical outcomes of patients with sepsis.
The quick SOFA score (qSOFA), developed by the Society of Critical Care and European Society of Intensive Care Medicine in 2016 guidelines, further helps hospitalists and other hospital physicians identify those patients at highest risk of mortality from sepsis outside an intensive care unit setting.
Dr. Kritek, who is a board-certified critical care medicine physician, has previously presented this talk at the Society for Hospital Medicine Annual Conference in the past. This year the presentation will include a number of studies that examine what role vitamin C, thiamine, and glucocorticoids have in treating patients with sepsis, she said. For example, it is thought that parenteral administration of vitamin C could raise plasma levels and reduce multiorgan failure. Thiamine could be useful in sepsis treatment because of its role in glucose metabolism and lactate production, while glucocorticoids could help improve the mortality rate of patients with sepsis.
While Dr. Kritek said she is not going to be advocating for the benefit of vitamin C and thiamine during the session, “this is an area of ongoing debate, and we will walk through the most recent data to try to make sense of it,” she said.
Dr. Kritek noted that the role of balanced crystalloids in resuscitation will be discussed versus when to use saline, as well as the potential of new vasopressors for the treatment of septic shock.
“Our goal will be to integrate the most recent literature into day-to-day practice,” Dr. Kritek said.Dr. Kritek reports no conflicts of interest.
“Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis”
Sepsis is the number one killer in U.S. hospitals. About one in three patient deaths in a hospital are attributable to sepsis, according to the Centers for Disease Control and Prevention, and it is the leading cause of readmission for U.S. hospitals as well.
Patricia Kritek MD, EdM, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, hopes to bring attendees up to speed on sepsis with her presentation, “Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis” at HM20 Virtual.
Each year, approximately 1.7 million American adults develop sepsis, and nearly 270,000 Americans will die from sepsis annually. Although sepsis disproportionately affects young children, older adults, patients with chronic diseases, and those with a weak immune system, the disease can affect anyone.
With that reputation, sepsis is on the forefront of hospitalists’ minds. Hospitalists are traditionally well versed in current sepsis guidelines, but time to treatment is paramount, and it can be difficult to stay up to date on the latest studies in the field.
The title of Dr. Kritek’s presentation hints at the theme: Hospitalists may have learned the systemic inflammatory response syndrome (SIRS) criteria for diagnosing sepsis, but the Sequential Organ Failure Assessment (SOFA) Score developed by the Third International Consensus Definitions for Sepsis and Septic Shock – previously known as the sepsis-related organ failure assessment score – has been the new method since 2016 to assess the clinical outcomes of patients with sepsis.
The quick SOFA score (qSOFA), developed by the Society of Critical Care and European Society of Intensive Care Medicine in 2016 guidelines, further helps hospitalists and other hospital physicians identify those patients at highest risk of mortality from sepsis outside an intensive care unit setting.
Dr. Kritek, who is a board-certified critical care medicine physician, has previously presented this talk at the Society for Hospital Medicine Annual Conference in the past. This year the presentation will include a number of studies that examine what role vitamin C, thiamine, and glucocorticoids have in treating patients with sepsis, she said. For example, it is thought that parenteral administration of vitamin C could raise plasma levels and reduce multiorgan failure. Thiamine could be useful in sepsis treatment because of its role in glucose metabolism and lactate production, while glucocorticoids could help improve the mortality rate of patients with sepsis.
While Dr. Kritek said she is not going to be advocating for the benefit of vitamin C and thiamine during the session, “this is an area of ongoing debate, and we will walk through the most recent data to try to make sense of it,” she said.
Dr. Kritek noted that the role of balanced crystalloids in resuscitation will be discussed versus when to use saline, as well as the potential of new vasopressors for the treatment of septic shock.
“Our goal will be to integrate the most recent literature into day-to-day practice,” Dr. Kritek said.Dr. Kritek reports no conflicts of interest.
“Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis”
Schools can reopen safely with precautions, experts say
The absence of in-person school has harmed children in ways beyond loss of academic learning, according to Josh Sharfstein, MD, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health, Baltimore. In addition to learning, school is a place where many children receive breakfast and lunch every day, as well as support services and the benefits of being in a safe and secure environment, Dr. Sharfstein said in a press briefing sponsored by Johns Hopkins University.
However, although it is an important priority for children to return to school, “we are in the midst of a pandemic that poses real risk,” he said.
In the press briefing, several experts shared ideas and considerations for safely reopening K-12 schools in the fall of 2020.
Data from other countries where schools have reopened, notably Austria and Denmark, have been reassuring about the lack of transmission of SARS-CoV-2 among children in a school setting, said Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins Center for Health Security. However, other countries where schools have reopened successfully have reported low levels of viral transmission locally, and a responsible strategy for school reopening in the United States should follow a similar plan, she said. In areas where transmission and infection rates are increasing “it may not be safe to reopen,” but in areas where rates are declining or stable, schools could potentially reopen if they follow safety measures.
Dr. Nuzzo suggested that Considerations include protocols for handwashing and sanitation, and maintaining physical distance by creative use of outdoor classrooms (weather permitting) or other spaces within school buildings. Transportation to and from school also will be an issue to address, she noted.
None of the strategies being considered will completely eliminate risk of SARS-CoV-2 infection in school settings, so allowing parents and students to opt out and choose distance learning will be important as well, said Dr. Nuzzo. In addition, schools may need to consider alternative roles for teachers and staff who don’t feel comfortable being in contact with students and fellow staff members. “All of these things are going to be hard,” Dr. Nuzzo acknowledged. “Hard should not be a deterrent,” to reopening schools, but “we acknowledge the resources that schools will need in order to do this.”
At present, all 50 states and the District of Columbia have released some type of plan for reopening schools, said Megan Collins, MD, MPH, codirector the Johns Hopkins Consortium for School-Based Health Solutions.
Dr. Collins and colleagues have developed a school reopening tracker, which is “a national snapshot of current reopening plans that have been released,” she said. The tracker is being updated continuously as plans evolve. The eSchool+ K-12 School Reopening Tracker identifies 12 reopening categories that states could potentially address in the plans. These categories are divided into Operational and Ethics/Equity. The operational categories include:
- Core academics
- SARS-CoV-2 protection
- Before and after school programs
- School access and transportation
- Student health services
- Food and nutrition.
Ethics/equity categories include the following:
- Parent choice
- Teacher and staff choice
- Children of poverty and systemic disadvantage
- Children with special needs/English as second language/gifted and twice exceptional
- Privacy
- Engagement and transparency.
As of July 15, 2020, 16 states (Arizona, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, North Carolina, North Dakota, Ohio, Rhode Island, Tennessee, Texas, Virginia, Washington, and Wisconsin) had addressed all 12 categories in their reopening plans, Dr. Collins said.
School reopening plans must take equity issues into account, said Annette Anderson, PhD, of the Johns Hopkins University School of Education.
Specifically, developing learning plans for special education students and others at the most risk for learning loss will be essential. “The digital divide has become a digital canyon” in some areas, Dr. Anderson noted, and schools need to rethink eligibility and work to provide access to devices for online learning for all students.
In addition, schools need to convince parents that schools are safe. She recommended that schools consider inviting parents and families to visit buildings in advance of reopening so they can see the safety measures, such as space between desks, cleaning stations, and other protective strategies.
The message to pediatricians and health care professionals when counseling families about returning individual children to school is to consider the risk to the child and the family directly in the context of the local plans, Dr. Sharfstein said during a question and answer session. “One school system’s plan is one school system’s plan,” he said, and added that families who are concerned about the risk should have an online option. However, “if you see a thoughtful approach” to reopening, with safety steps taken and parents informed, with protocols such as keeping small groups of children together to reduce transmission, “it is a pretty good trade-off,” and that is why the American Academy of Pediatrics currently favors children returning to school, he said.
The briefing participants had no relevant financial conflicts to disclose.
The absence of in-person school has harmed children in ways beyond loss of academic learning, according to Josh Sharfstein, MD, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health, Baltimore. In addition to learning, school is a place where many children receive breakfast and lunch every day, as well as support services and the benefits of being in a safe and secure environment, Dr. Sharfstein said in a press briefing sponsored by Johns Hopkins University.
However, although it is an important priority for children to return to school, “we are in the midst of a pandemic that poses real risk,” he said.
In the press briefing, several experts shared ideas and considerations for safely reopening K-12 schools in the fall of 2020.
Data from other countries where schools have reopened, notably Austria and Denmark, have been reassuring about the lack of transmission of SARS-CoV-2 among children in a school setting, said Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins Center for Health Security. However, other countries where schools have reopened successfully have reported low levels of viral transmission locally, and a responsible strategy for school reopening in the United States should follow a similar plan, she said. In areas where transmission and infection rates are increasing “it may not be safe to reopen,” but in areas where rates are declining or stable, schools could potentially reopen if they follow safety measures.
Dr. Nuzzo suggested that Considerations include protocols for handwashing and sanitation, and maintaining physical distance by creative use of outdoor classrooms (weather permitting) or other spaces within school buildings. Transportation to and from school also will be an issue to address, she noted.
None of the strategies being considered will completely eliminate risk of SARS-CoV-2 infection in school settings, so allowing parents and students to opt out and choose distance learning will be important as well, said Dr. Nuzzo. In addition, schools may need to consider alternative roles for teachers and staff who don’t feel comfortable being in contact with students and fellow staff members. “All of these things are going to be hard,” Dr. Nuzzo acknowledged. “Hard should not be a deterrent,” to reopening schools, but “we acknowledge the resources that schools will need in order to do this.”
At present, all 50 states and the District of Columbia have released some type of plan for reopening schools, said Megan Collins, MD, MPH, codirector the Johns Hopkins Consortium for School-Based Health Solutions.
Dr. Collins and colleagues have developed a school reopening tracker, which is “a national snapshot of current reopening plans that have been released,” she said. The tracker is being updated continuously as plans evolve. The eSchool+ K-12 School Reopening Tracker identifies 12 reopening categories that states could potentially address in the plans. These categories are divided into Operational and Ethics/Equity. The operational categories include:
- Core academics
- SARS-CoV-2 protection
- Before and after school programs
- School access and transportation
- Student health services
- Food and nutrition.
Ethics/equity categories include the following:
- Parent choice
- Teacher and staff choice
- Children of poverty and systemic disadvantage
- Children with special needs/English as second language/gifted and twice exceptional
- Privacy
- Engagement and transparency.
As of July 15, 2020, 16 states (Arizona, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, North Carolina, North Dakota, Ohio, Rhode Island, Tennessee, Texas, Virginia, Washington, and Wisconsin) had addressed all 12 categories in their reopening plans, Dr. Collins said.
School reopening plans must take equity issues into account, said Annette Anderson, PhD, of the Johns Hopkins University School of Education.
Specifically, developing learning plans for special education students and others at the most risk for learning loss will be essential. “The digital divide has become a digital canyon” in some areas, Dr. Anderson noted, and schools need to rethink eligibility and work to provide access to devices for online learning for all students.
In addition, schools need to convince parents that schools are safe. She recommended that schools consider inviting parents and families to visit buildings in advance of reopening so they can see the safety measures, such as space between desks, cleaning stations, and other protective strategies.
The message to pediatricians and health care professionals when counseling families about returning individual children to school is to consider the risk to the child and the family directly in the context of the local plans, Dr. Sharfstein said during a question and answer session. “One school system’s plan is one school system’s plan,” he said, and added that families who are concerned about the risk should have an online option. However, “if you see a thoughtful approach” to reopening, with safety steps taken and parents informed, with protocols such as keeping small groups of children together to reduce transmission, “it is a pretty good trade-off,” and that is why the American Academy of Pediatrics currently favors children returning to school, he said.
The briefing participants had no relevant financial conflicts to disclose.
The absence of in-person school has harmed children in ways beyond loss of academic learning, according to Josh Sharfstein, MD, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health, Baltimore. In addition to learning, school is a place where many children receive breakfast and lunch every day, as well as support services and the benefits of being in a safe and secure environment, Dr. Sharfstein said in a press briefing sponsored by Johns Hopkins University.
However, although it is an important priority for children to return to school, “we are in the midst of a pandemic that poses real risk,” he said.
In the press briefing, several experts shared ideas and considerations for safely reopening K-12 schools in the fall of 2020.
Data from other countries where schools have reopened, notably Austria and Denmark, have been reassuring about the lack of transmission of SARS-CoV-2 among children in a school setting, said Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins Center for Health Security. However, other countries where schools have reopened successfully have reported low levels of viral transmission locally, and a responsible strategy for school reopening in the United States should follow a similar plan, she said. In areas where transmission and infection rates are increasing “it may not be safe to reopen,” but in areas where rates are declining or stable, schools could potentially reopen if they follow safety measures.
Dr. Nuzzo suggested that Considerations include protocols for handwashing and sanitation, and maintaining physical distance by creative use of outdoor classrooms (weather permitting) or other spaces within school buildings. Transportation to and from school also will be an issue to address, she noted.
None of the strategies being considered will completely eliminate risk of SARS-CoV-2 infection in school settings, so allowing parents and students to opt out and choose distance learning will be important as well, said Dr. Nuzzo. In addition, schools may need to consider alternative roles for teachers and staff who don’t feel comfortable being in contact with students and fellow staff members. “All of these things are going to be hard,” Dr. Nuzzo acknowledged. “Hard should not be a deterrent,” to reopening schools, but “we acknowledge the resources that schools will need in order to do this.”
At present, all 50 states and the District of Columbia have released some type of plan for reopening schools, said Megan Collins, MD, MPH, codirector the Johns Hopkins Consortium for School-Based Health Solutions.
Dr. Collins and colleagues have developed a school reopening tracker, which is “a national snapshot of current reopening plans that have been released,” she said. The tracker is being updated continuously as plans evolve. The eSchool+ K-12 School Reopening Tracker identifies 12 reopening categories that states could potentially address in the plans. These categories are divided into Operational and Ethics/Equity. The operational categories include:
- Core academics
- SARS-CoV-2 protection
- Before and after school programs
- School access and transportation
- Student health services
- Food and nutrition.
Ethics/equity categories include the following:
- Parent choice
- Teacher and staff choice
- Children of poverty and systemic disadvantage
- Children with special needs/English as second language/gifted and twice exceptional
- Privacy
- Engagement and transparency.
As of July 15, 2020, 16 states (Arizona, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, North Carolina, North Dakota, Ohio, Rhode Island, Tennessee, Texas, Virginia, Washington, and Wisconsin) had addressed all 12 categories in their reopening plans, Dr. Collins said.
School reopening plans must take equity issues into account, said Annette Anderson, PhD, of the Johns Hopkins University School of Education.
Specifically, developing learning plans for special education students and others at the most risk for learning loss will be essential. “The digital divide has become a digital canyon” in some areas, Dr. Anderson noted, and schools need to rethink eligibility and work to provide access to devices for online learning for all students.
In addition, schools need to convince parents that schools are safe. She recommended that schools consider inviting parents and families to visit buildings in advance of reopening so they can see the safety measures, such as space between desks, cleaning stations, and other protective strategies.
The message to pediatricians and health care professionals when counseling families about returning individual children to school is to consider the risk to the child and the family directly in the context of the local plans, Dr. Sharfstein said during a question and answer session. “One school system’s plan is one school system’s plan,” he said, and added that families who are concerned about the risk should have an online option. However, “if you see a thoughtful approach” to reopening, with safety steps taken and parents informed, with protocols such as keeping small groups of children together to reduce transmission, “it is a pretty good trade-off,” and that is why the American Academy of Pediatrics currently favors children returning to school, he said.
The briefing participants had no relevant financial conflicts to disclose.