Antimicrobial-resistant infections

The first strain of Escherichia coli harboring the antibiotic-resistant genes mcr-1 and bla_NDM-5 was isolated in the urine of a U.S. patient, according to a report in mBio.

A 76-year-old man was admitted to a tertiary-care hospital in New Jersey with a fever and flank pain in August 2014. The patient emigrated from India and resided in the United States for 1 year prior to this presentation. He had a history of prostate cancer treated with radiation therapy and subsequently developed recurrent urinary tract infections. He had also experienced bladder perforation requiring bilateral placement of nephrostomy tubes, which were clamped 5 days prior to presentation.

Manjurul/Thinkstock

[email protected]

The first strain of Escherichia coli harboring the antibiotic-resistant genes mcr-1 and bla_NDM-5 was isolated in the urine of a U.S. patient, according to a report in mBio.

A 76-year-old man was admitted to a tertiary-care hospital in New Jersey with a fever and flank pain in August 2014. The patient emigrated from India and resided in the United States for 1 year prior to this presentation. He had a history of prostate cancer treated with radiation therapy and subsequently developed recurrent urinary tract infections. He had also experienced bladder perforation requiring bilateral placement of nephrostomy tubes, which were clamped 5 days prior to presentation.

Manjurul/Thinkstock

[email protected]

The first strain of Escherichia coli harboring the antibiotic-resistant genes mcr-1 and bla_NDM-5 was isolated in the urine of a U.S. patient, according to a report in mBio.

A 76-year-old man was admitted to a tertiary-care hospital in New Jersey with a fever and flank pain in August 2014. The patient emigrated from India and resided in the United States for 1 year prior to this presentation. He had a history of prostate cancer treated with radiation therapy and subsequently developed recurrent urinary tract infections. He had also experienced bladder perforation requiring bilateral placement of nephrostomy tubes, which were clamped 5 days prior to presentation.

Manjurul/Thinkstock

[email protected]

Carbapenem-resistant Enterobacteriaceae (CRE) are extremely drug-resistant organisms. According to the Centers for Disease Control and Prevention’s National Healthcare Safety Network, in 2014 in the United States, 3.6% of Enterobacteriaceae causing hospital-acquired infections were resistant to carbapenems.¹ Antibiotic treatment options for CRE infections are severely limited, and mortality for invasive infections can be as high as 40%-50%.²

Resistance to carbapenems can be mediated by several mechanisms. From an epidemiologic standpoint, production of carbapenemases is the most-threatening mechanism because Enterobacteriaceae-harboring carbapenemases are highly transmissible.

Carbapenemase-producing CRE (CP-CRE) have caused large outbreaks throughout the world. Israel experienced a nationwide outbreak of CP-CRE, primarily Klebsiella pneumoniae carbapenemase–producing Klebsiella pneumoniae, in the mid-2000s. At the peak of the outbreak in 2007, there were 185 new cases per month (55.5/100,000 patient-days). A successful intervention at the national level dramatically decreased the incidence to 4.8/100,000 patient days in 2012.³

One component of the intervention (which is still ongoing) is active surveillance of high-risk groups using rectal swabs. Upon admission to the hospital, we screen patients who were recently in other hospitals or long-term care facilities. In addition, when a patient is newly diagnosed with CP-CRE (either asymptomatic carriage or clinical infection), we screen patients who had contact with that index case before isolation measures were implemented.

We recently published a study in Infection Control and Hospital Epidemiology that draws on our experience with CP-CRE screening of contacts at Tel Aviv Sourasky Medical Center.⁴ Both Israeli and International guidelines do not precisely define which contacts of a CP-CRE index case warrant screening. For example, should only roommates of index cases be screened or should we screen all patients on the same ward as the index case? Likewise, is there a minimum time of contact that should trigger screening?

Identifying which contacts are at high risk of acquiring CP-CRE is important for two reasons: We want to detect contacts who acquired CP-CRE so that they can be isolated before further transmission occurs, and we don’t want to waste resources and screen those at low risk. In our hospital, the criteria for being a contact are staying in the same ward and being treated by the same nursing staff as a newly identified CP-CRE patient.

This strategy appears to lead to overscreening, as we found that from October 2008 to June 2012, 3,158 screening tests were performed to detect 53 positive contacts (a yield of less than 2%). In order to screen more efficiently, our study aimed to determine risk factors for CP-CRE acquisition among patients exposed to a CP-CRE index patient.

We used a matched case-control design. The case group consisted of the 53 contacts who screened positive for CP-CRE. For each case we chose 2 controls: contacts who screened negative for CP-CRE. The basis for matching between the case and the 2 controls was that they were exposed to the same index patient. The benefit of matching this way was that it eliminated the question of whether a contact became positive because the index patient was more likely to transmit CP-CRE (e.g., because of diarrhea), and not because of characteristics of the contact patients themselves.

We found three factors that increased the risk that a contact would screen positive:

• Contact period of at least 3 days with the index case.

• Being on mechanical ventilation.

• Having a history of carriage or infection with another multidrug-resistant organism (such as methicillin-resistant Staphylococcus aureus).

Unexpectedly, sharing a room with the index patient or being debilitated did not significantly increase the risk of acquiring CP-CRE.

Many studies have identified antibiotic use as a risk factor for acquiring CP-CRE. In our study, no class of antibiotic increased the risk of CP-CRE acquisition, probably because only a small number of patients received each class. We were surprised to find that contacts who had taken cephalosporins were less likely to acquire CP-CRE. On further examination, when we compared patients who received only cephalosporins with patients who received no antibiotic, this protective effect disappeared. Nevertheless, compared with other antibiotics, it appears that cephalosporins might pose less of a risk for CP-CRE acquisition. More studies are needed to confirm our findings.

Our findings have practical implications for infection control. Using the risk factors we identified could help us to avoid excessive screening. We calculated that selective screening, based on our three risk factors, would have decreased the number of contacts screened by 30%, but 2 out of 53 positive contacts would have been missed. Institutions need to decide whether that is a trade-off they are willing to make.

Another way to apply our findings could be to add an additional layer of infection control by preemptively implementing contact precautions for patients at highest risk, for example, those with more than one risk factor.
 

1. Weiner LM, Fridkin SK, Aponte-Torres Z, Avery L, Coffin N, Dudeck MA, Edwards JR, Jernigan JA, Konnor R, Soe MM, Peterson K, Clifford McDonald L. Vital signs: preventing antibiotic-resistant infections in hospitals - United States, 2014. Am J Transplant. 2016 Jul;16(7):2224-30.

2. Centers for Disease Control and Prevention. Facility guidance for control of carbapenem-resistant Enterobacteriaceae (CRE): November 2015 update – CRE Toolkit.

3. Schwaber MJ, Carmeli Y. An ongoing national intervention to contain the spread of carbapenem-resistant enterobacteriaceae. Clin Infect Dis. 2014 Mar;58(5):697-703.

Schwartz-Neiderman A, Braun T, Fallach N, Schwartz D, Carmeli Y, Schechner V. Risk factors for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) acquisition among contacts of newly diagnosed CP-CRE patients. Infect Control Hosp Epidemiol. 2016 Jul 25:1-7.
 

Vered Schechner, MD, MSc, is an infection control physician in the department of epidemiology at Tel Aviv Sourasky Medical Center.

Carbapenem-resistant Enterobacteriaceae (CRE) are extremely drug-resistant organisms. According to the Centers for Disease Control and Prevention’s National Healthcare Safety Network, in 2014 in the United States, 3.6% of Enterobacteriaceae causing hospital-acquired infections were resistant to carbapenems.¹ Antibiotic treatment options for CRE infections are severely limited, and mortality for invasive infections can be as high as 40%-50%.²

Resistance to carbapenems can be mediated by several mechanisms. From an epidemiologic standpoint, production of carbapenemases is the most-threatening mechanism because Enterobacteriaceae-harboring carbapenemases are highly transmissible.

Carbapenemase-producing CRE (CP-CRE) have caused large outbreaks throughout the world. Israel experienced a nationwide outbreak of CP-CRE, primarily Klebsiella pneumoniae carbapenemase–producing Klebsiella pneumoniae, in the mid-2000s. At the peak of the outbreak in 2007, there were 185 new cases per month (55.5/100,000 patient-days). A successful intervention at the national level dramatically decreased the incidence to 4.8/100,000 patient days in 2012.³

One component of the intervention (which is still ongoing) is active surveillance of high-risk groups using rectal swabs. Upon admission to the hospital, we screen patients who were recently in other hospitals or long-term care facilities. In addition, when a patient is newly diagnosed with CP-CRE (either asymptomatic carriage or clinical infection), we screen patients who had contact with that index case before isolation measures were implemented.

We recently published a study in Infection Control and Hospital Epidemiology that draws on our experience with CP-CRE screening of contacts at Tel Aviv Sourasky Medical Center.⁴ Both Israeli and International guidelines do not precisely define which contacts of a CP-CRE index case warrant screening. For example, should only roommates of index cases be screened or should we screen all patients on the same ward as the index case? Likewise, is there a minimum time of contact that should trigger screening?

Identifying which contacts are at high risk of acquiring CP-CRE is important for two reasons: We want to detect contacts who acquired CP-CRE so that they can be isolated before further transmission occurs, and we don’t want to waste resources and screen those at low risk. In our hospital, the criteria for being a contact are staying in the same ward and being treated by the same nursing staff as a newly identified CP-CRE patient.

This strategy appears to lead to overscreening, as we found that from October 2008 to June 2012, 3,158 screening tests were performed to detect 53 positive contacts (a yield of less than 2%). In order to screen more efficiently, our study aimed to determine risk factors for CP-CRE acquisition among patients exposed to a CP-CRE index patient.

We used a matched case-control design. The case group consisted of the 53 contacts who screened positive for CP-CRE. For each case we chose 2 controls: contacts who screened negative for CP-CRE. The basis for matching between the case and the 2 controls was that they were exposed to the same index patient. The benefit of matching this way was that it eliminated the question of whether a contact became positive because the index patient was more likely to transmit CP-CRE (e.g., because of diarrhea), and not because of characteristics of the contact patients themselves.

We found three factors that increased the risk that a contact would screen positive:

• Contact period of at least 3 days with the index case.

• Being on mechanical ventilation.

• Having a history of carriage or infection with another multidrug-resistant organism (such as methicillin-resistant Staphylococcus aureus).

Unexpectedly, sharing a room with the index patient or being debilitated did not significantly increase the risk of acquiring CP-CRE.

Many studies have identified antibiotic use as a risk factor for acquiring CP-CRE. In our study, no class of antibiotic increased the risk of CP-CRE acquisition, probably because only a small number of patients received each class. We were surprised to find that contacts who had taken cephalosporins were less likely to acquire CP-CRE. On further examination, when we compared patients who received only cephalosporins with patients who received no antibiotic, this protective effect disappeared. Nevertheless, compared with other antibiotics, it appears that cephalosporins might pose less of a risk for CP-CRE acquisition. More studies are needed to confirm our findings.

Our findings have practical implications for infection control. Using the risk factors we identified could help us to avoid excessive screening. We calculated that selective screening, based on our three risk factors, would have decreased the number of contacts screened by 30%, but 2 out of 53 positive contacts would have been missed. Institutions need to decide whether that is a trade-off they are willing to make.

Another way to apply our findings could be to add an additional layer of infection control by preemptively implementing contact precautions for patients at highest risk, for example, those with more than one risk factor.
 

1. Weiner LM, Fridkin SK, Aponte-Torres Z, Avery L, Coffin N, Dudeck MA, Edwards JR, Jernigan JA, Konnor R, Soe MM, Peterson K, Clifford McDonald L. Vital signs: preventing antibiotic-resistant infections in hospitals - United States, 2014. Am J Transplant. 2016 Jul;16(7):2224-30.

2. Centers for Disease Control and Prevention. Facility guidance for control of carbapenem-resistant Enterobacteriaceae (CRE): November 2015 update – CRE Toolkit.

3. Schwaber MJ, Carmeli Y. An ongoing national intervention to contain the spread of carbapenem-resistant enterobacteriaceae. Clin Infect Dis. 2014 Mar;58(5):697-703.

Schwartz-Neiderman A, Braun T, Fallach N, Schwartz D, Carmeli Y, Schechner V. Risk factors for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) acquisition among contacts of newly diagnosed CP-CRE patients. Infect Control Hosp Epidemiol. 2016 Jul 25:1-7.
 

Vered Schechner, MD, MSc, is an infection control physician in the department of epidemiology at Tel Aviv Sourasky Medical Center.

Carbapenem-resistant Enterobacteriaceae (CRE) are extremely drug-resistant organisms. According to the Centers for Disease Control and Prevention’s National Healthcare Safety Network, in 2014 in the United States, 3.6% of Enterobacteriaceae causing hospital-acquired infections were resistant to carbapenems.¹ Antibiotic treatment options for CRE infections are severely limited, and mortality for invasive infections can be as high as 40%-50%.²

Resistance to carbapenems can be mediated by several mechanisms. From an epidemiologic standpoint, production of carbapenemases is the most-threatening mechanism because Enterobacteriaceae-harboring carbapenemases are highly transmissible.

Carbapenemase-producing CRE (CP-CRE) have caused large outbreaks throughout the world. Israel experienced a nationwide outbreak of CP-CRE, primarily Klebsiella pneumoniae carbapenemase–producing Klebsiella pneumoniae, in the mid-2000s. At the peak of the outbreak in 2007, there were 185 new cases per month (55.5/100,000 patient-days). A successful intervention at the national level dramatically decreased the incidence to 4.8/100,000 patient days in 2012.³

One component of the intervention (which is still ongoing) is active surveillance of high-risk groups using rectal swabs. Upon admission to the hospital, we screen patients who were recently in other hospitals or long-term care facilities. In addition, when a patient is newly diagnosed with CP-CRE (either asymptomatic carriage or clinical infection), we screen patients who had contact with that index case before isolation measures were implemented.

We recently published a study in Infection Control and Hospital Epidemiology that draws on our experience with CP-CRE screening of contacts at Tel Aviv Sourasky Medical Center.⁴ Both Israeli and International guidelines do not precisely define which contacts of a CP-CRE index case warrant screening. For example, should only roommates of index cases be screened or should we screen all patients on the same ward as the index case? Likewise, is there a minimum time of contact that should trigger screening?

Identifying which contacts are at high risk of acquiring CP-CRE is important for two reasons: We want to detect contacts who acquired CP-CRE so that they can be isolated before further transmission occurs, and we don’t want to waste resources and screen those at low risk. In our hospital, the criteria for being a contact are staying in the same ward and being treated by the same nursing staff as a newly identified CP-CRE patient.

This strategy appears to lead to overscreening, as we found that from October 2008 to June 2012, 3,158 screening tests were performed to detect 53 positive contacts (a yield of less than 2%). In order to screen more efficiently, our study aimed to determine risk factors for CP-CRE acquisition among patients exposed to a CP-CRE index patient.

We used a matched case-control design. The case group consisted of the 53 contacts who screened positive for CP-CRE. For each case we chose 2 controls: contacts who screened negative for CP-CRE. The basis for matching between the case and the 2 controls was that they were exposed to the same index patient. The benefit of matching this way was that it eliminated the question of whether a contact became positive because the index patient was more likely to transmit CP-CRE (e.g., because of diarrhea), and not because of characteristics of the contact patients themselves.

We found three factors that increased the risk that a contact would screen positive:

• Contact period of at least 3 days with the index case.

• Being on mechanical ventilation.

• Having a history of carriage or infection with another multidrug-resistant organism (such as methicillin-resistant Staphylococcus aureus).

Unexpectedly, sharing a room with the index patient or being debilitated did not significantly increase the risk of acquiring CP-CRE.

Many studies have identified antibiotic use as a risk factor for acquiring CP-CRE. In our study, no class of antibiotic increased the risk of CP-CRE acquisition, probably because only a small number of patients received each class. We were surprised to find that contacts who had taken cephalosporins were less likely to acquire CP-CRE. On further examination, when we compared patients who received only cephalosporins with patients who received no antibiotic, this protective effect disappeared. Nevertheless, compared with other antibiotics, it appears that cephalosporins might pose less of a risk for CP-CRE acquisition. More studies are needed to confirm our findings.

Our findings have practical implications for infection control. Using the risk factors we identified could help us to avoid excessive screening. We calculated that selective screening, based on our three risk factors, would have decreased the number of contacts screened by 30%, but 2 out of 53 positive contacts would have been missed. Institutions need to decide whether that is a trade-off they are willing to make.

Another way to apply our findings could be to add an additional layer of infection control by preemptively implementing contact precautions for patients at highest risk, for example, those with more than one risk factor.
 

1. Weiner LM, Fridkin SK, Aponte-Torres Z, Avery L, Coffin N, Dudeck MA, Edwards JR, Jernigan JA, Konnor R, Soe MM, Peterson K, Clifford McDonald L. Vital signs: preventing antibiotic-resistant infections in hospitals - United States, 2014. Am J Transplant. 2016 Jul;16(7):2224-30.

2. Centers for Disease Control and Prevention. Facility guidance for control of carbapenem-resistant Enterobacteriaceae (CRE): November 2015 update – CRE Toolkit.

3. Schwaber MJ, Carmeli Y. An ongoing national intervention to contain the spread of carbapenem-resistant enterobacteriaceae. Clin Infect Dis. 2014 Mar;58(5):697-703.

Schwartz-Neiderman A, Braun T, Fallach N, Schwartz D, Carmeli Y, Schechner V. Risk factors for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) acquisition among contacts of newly diagnosed CP-CRE patients. Infect Control Hosp Epidemiol. 2016 Jul 25:1-7.
 

Vered Schechner, MD, MSc, is an infection control physician in the department of epidemiology at Tel Aviv Sourasky Medical Center.

Intravenous ceftazidime-avibactam successfully treated 59% of carbapenem-resistant Enterobacteriaceae (CRE) infections, and 76% of patients remained alive at 30 days, according to a retrospective cohort study published in Clinical Infectious Diseases.

Those rates resemble previous reports of treatment with in vitro active agents, while the rate of acute kidney injury was about a third lower, said Ryan K. Shields, PharmD, of the University of Pittsburgh, and his associates. But 8% of CRE infections developed ceftazidime-avibactam resistance, which accounted for about a third of microbiological failures, the researchers said. “It is incumbent upon health care providers to share their clinical experiences with ceftazidime-avibactam and other new beta-lactamase inhibitors, so these agents can be used most effectively for the longest period of time,” they added.

James Gathany/CDC

Ceftazidime-avibactam (Avycaz) is a novel beta-lactam/beta-lactamase inhibitor combination approved by the Food and Drug Administration in 2015 for complicated intra-abdominal and urinary tract infections. It was hoped that the newly approved combination would prove safer and more effective than previously developed agents that showed in vitro activity against CRE, such as colistin, gentamicin, and tigecycline, the researchers noted.

They described CRE-infected patients treated with ceftazidime-avibactam (median, 14 days; range, 4-71 days) between April 2015 and February 2016. The average age of the patients was 64 years (range 26-78 years), and 57% were men. Infections included ventilator or health care–associated pneumonia, primary bacteremia, intra-abdominal infection, skin and soft tissue infections, pyelonephritis, mediastinitis, subdural empyema/ventriculitis, and purulent tracheobronchitis. All the CRE isolates were susceptible to ceftazidime-avibactam at baseline. In all, 70% of patients received ceftazidime-avibactam as monotherapy, while 30% received it in combination with intravenous or inhaled gentamicin, intravenous or intrathecal colistin, or tigecycline (Clin Infect Dis. 2016 Sep 13. doi: 10.1093/cid/ciw636).

A total of 28 (76%) patients were alive at 30 days and 62% were alive at 90 days, the investigators said. They calculated a 59% rate of clinical success, defined as absence of recurrence within 30 days of onset, resolution of signs and symptoms, and sterilization of site-specific cultures within 7 days of treatment. Combination therapy did not improve the chances of clinical success, they noted. Among the 15 clinical failures, 9 patients died, 4 developed recurrent CRE infections, and 2 did not clinically improve. Clinical success was less likely when patients needed continuous renal replacement therapy (17% vs. 68% for other patients; P = .03) or had higher Sequential Organ Failure Assessment (SOFA) scores (average, 5.2 in clinical successes vs. 8.8 in clinical failures; P = .047). In addition, 10% of patients developed acute kidney injury within 7 days of starting treatment, which was “considerably lower than the approximately 30% rate we previously reported with carbapenem-colistin or aminoglycoside-based combinations,” the investigators said.

The sample size was too small to definitively answer questions about whether combination regimens can overcome resistance, improve outcomes, or effectively treat specific types of CRE infection, the researchers noted. “Nevertheless, we can conclude that ceftazidime-avibactam offers an important advance in the treatment of CRE infections,” they wrote. “The development of resistance after as few as 10 days of therapy is troubling, and treatment failures and deaths in a significant minority of patients highlight the need for more agents with activity against CRE.”

The University of Pittsburgh Medical Center and the National Institutes of Health provided funding. One coauthor disclosed ties to Meiji, Shionogi, Tetraphase, Achaogen, Merck, and The Medicines Company. The other authors had no disclosures.

Intravenous ceftazidime-avibactam successfully treated 59% of carbapenem-resistant Enterobacteriaceae (CRE) infections, and 76% of patients remained alive at 30 days, according to a retrospective cohort study published in Clinical Infectious Diseases.

Those rates resemble previous reports of treatment with in vitro active agents, while the rate of acute kidney injury was about a third lower, said Ryan K. Shields, PharmD, of the University of Pittsburgh, and his associates. But 8% of CRE infections developed ceftazidime-avibactam resistance, which accounted for about a third of microbiological failures, the researchers said. “It is incumbent upon health care providers to share their clinical experiences with ceftazidime-avibactam and other new beta-lactamase inhibitors, so these agents can be used most effectively for the longest period of time,” they added.

James Gathany/CDC

Ceftazidime-avibactam (Avycaz) is a novel beta-lactam/beta-lactamase inhibitor combination approved by the Food and Drug Administration in 2015 for complicated intra-abdominal and urinary tract infections. It was hoped that the newly approved combination would prove safer and more effective than previously developed agents that showed in vitro activity against CRE, such as colistin, gentamicin, and tigecycline, the researchers noted.

They described CRE-infected patients treated with ceftazidime-avibactam (median, 14 days; range, 4-71 days) between April 2015 and February 2016. The average age of the patients was 64 years (range 26-78 years), and 57% were men. Infections included ventilator or health care–associated pneumonia, primary bacteremia, intra-abdominal infection, skin and soft tissue infections, pyelonephritis, mediastinitis, subdural empyema/ventriculitis, and purulent tracheobronchitis. All the CRE isolates were susceptible to ceftazidime-avibactam at baseline. In all, 70% of patients received ceftazidime-avibactam as monotherapy, while 30% received it in combination with intravenous or inhaled gentamicin, intravenous or intrathecal colistin, or tigecycline (Clin Infect Dis. 2016 Sep 13. doi: 10.1093/cid/ciw636).

A total of 28 (76%) patients were alive at 30 days and 62% were alive at 90 days, the investigators said. They calculated a 59% rate of clinical success, defined as absence of recurrence within 30 days of onset, resolution of signs and symptoms, and sterilization of site-specific cultures within 7 days of treatment. Combination therapy did not improve the chances of clinical success, they noted. Among the 15 clinical failures, 9 patients died, 4 developed recurrent CRE infections, and 2 did not clinically improve. Clinical success was less likely when patients needed continuous renal replacement therapy (17% vs. 68% for other patients; P = .03) or had higher Sequential Organ Failure Assessment (SOFA) scores (average, 5.2 in clinical successes vs. 8.8 in clinical failures; P = .047). In addition, 10% of patients developed acute kidney injury within 7 days of starting treatment, which was “considerably lower than the approximately 30% rate we previously reported with carbapenem-colistin or aminoglycoside-based combinations,” the investigators said.

The sample size was too small to definitively answer questions about whether combination regimens can overcome resistance, improve outcomes, or effectively treat specific types of CRE infection, the researchers noted. “Nevertheless, we can conclude that ceftazidime-avibactam offers an important advance in the treatment of CRE infections,” they wrote. “The development of resistance after as few as 10 days of therapy is troubling, and treatment failures and deaths in a significant minority of patients highlight the need for more agents with activity against CRE.”

The University of Pittsburgh Medical Center and the National Institutes of Health provided funding. One coauthor disclosed ties to Meiji, Shionogi, Tetraphase, Achaogen, Merck, and The Medicines Company. The other authors had no disclosures.

Intravenous ceftazidime-avibactam successfully treated 59% of carbapenem-resistant Enterobacteriaceae (CRE) infections, and 76% of patients remained alive at 30 days, according to a retrospective cohort study published in Clinical Infectious Diseases.

Those rates resemble previous reports of treatment with in vitro active agents, while the rate of acute kidney injury was about a third lower, said Ryan K. Shields, PharmD, of the University of Pittsburgh, and his associates. But 8% of CRE infections developed ceftazidime-avibactam resistance, which accounted for about a third of microbiological failures, the researchers said. “It is incumbent upon health care providers to share their clinical experiences with ceftazidime-avibactam and other new beta-lactamase inhibitors, so these agents can be used most effectively for the longest period of time,” they added.

James Gathany/CDC

Ceftazidime-avibactam (Avycaz) is a novel beta-lactam/beta-lactamase inhibitor combination approved by the Food and Drug Administration in 2015 for complicated intra-abdominal and urinary tract infections. It was hoped that the newly approved combination would prove safer and more effective than previously developed agents that showed in vitro activity against CRE, such as colistin, gentamicin, and tigecycline, the researchers noted.

They described CRE-infected patients treated with ceftazidime-avibactam (median, 14 days; range, 4-71 days) between April 2015 and February 2016. The average age of the patients was 64 years (range 26-78 years), and 57% were men. Infections included ventilator or health care–associated pneumonia, primary bacteremia, intra-abdominal infection, skin and soft tissue infections, pyelonephritis, mediastinitis, subdural empyema/ventriculitis, and purulent tracheobronchitis. All the CRE isolates were susceptible to ceftazidime-avibactam at baseline. In all, 70% of patients received ceftazidime-avibactam as monotherapy, while 30% received it in combination with intravenous or inhaled gentamicin, intravenous or intrathecal colistin, or tigecycline (Clin Infect Dis. 2016 Sep 13. doi: 10.1093/cid/ciw636).

A total of 28 (76%) patients were alive at 30 days and 62% were alive at 90 days, the investigators said. They calculated a 59% rate of clinical success, defined as absence of recurrence within 30 days of onset, resolution of signs and symptoms, and sterilization of site-specific cultures within 7 days of treatment. Combination therapy did not improve the chances of clinical success, they noted. Among the 15 clinical failures, 9 patients died, 4 developed recurrent CRE infections, and 2 did not clinically improve. Clinical success was less likely when patients needed continuous renal replacement therapy (17% vs. 68% for other patients; P = .03) or had higher Sequential Organ Failure Assessment (SOFA) scores (average, 5.2 in clinical successes vs. 8.8 in clinical failures; P = .047). In addition, 10% of patients developed acute kidney injury within 7 days of starting treatment, which was “considerably lower than the approximately 30% rate we previously reported with carbapenem-colistin or aminoglycoside-based combinations,” the investigators said.

The sample size was too small to definitively answer questions about whether combination regimens can overcome resistance, improve outcomes, or effectively treat specific types of CRE infection, the researchers noted. “Nevertheless, we can conclude that ceftazidime-avibactam offers an important advance in the treatment of CRE infections,” they wrote. “The development of resistance after as few as 10 days of therapy is troubling, and treatment failures and deaths in a significant minority of patients highlight the need for more agents with activity against CRE.”

The University of Pittsburgh Medical Center and the National Institutes of Health provided funding. One coauthor disclosed ties to Meiji, Shionogi, Tetraphase, Achaogen, Merck, and The Medicines Company. The other authors had no disclosures.

The Food and Drug Administration has released a draft guidance document intended to help drug sponsors and device manufacturers coordinate the development of new antimicrobial drugs and antimicrobial susceptibility test devices (ASTs).

The FDA said it wants the guidance document, entitled “Coordinated Development of Antimicrobial Drugs and Antimicrobial Susceptibility Test Devices,” to help harmonize “development of these products such that the AST device could be cleared either at the time of new drug approval or shortly thereafter.” The agency acknowledged in the guidance document that development of antimicrobial drugs and ASTs – which test for in vitro susceptibility of bacterial pathogens isolated from clinical specimens to antimicrobials – has traditionally occurred independently, with AST device development “often initiated following drug approval.” A coordinated approach to developing new antimicrobial drugs with AST devices ideally would minimize the time between the approval of a new antimicrobial drug and clearance of an AST device.

The FDA highlighted three key goals of the guidance document:

• Describe interactions between antimicrobial drug sponsors and AST device manufacturers to help improve coordinated development of a new antimicrobial drug and an AST device to streamline the clearance process.

• Explain the considerations for submitting separate applications to the Center for Drug Evaluation and Research and the Center for Devices and Radiological Health when seeking to facilitate clearance of an AST device as close in time as possible to antimicrobial drug approval.

• Emphasize that the review of the new antimicrobial drug product and AST device(s) will remain independent, and that coordinated development does not influence the review timelines for either product.

The FDA will accept comments and suggestions on the draft guidance document within 60 days of publication in the Federal Register.

[email protected]

On Twitter @richpizzi

The Food and Drug Administration has released a draft guidance document intended to help drug sponsors and device manufacturers coordinate the development of new antimicrobial drugs and antimicrobial susceptibility test devices (ASTs).

The FDA said it wants the guidance document, entitled “Coordinated Development of Antimicrobial Drugs and Antimicrobial Susceptibility Test Devices,” to help harmonize “development of these products such that the AST device could be cleared either at the time of new drug approval or shortly thereafter.” The agency acknowledged in the guidance document that development of antimicrobial drugs and ASTs – which test for in vitro susceptibility of bacterial pathogens isolated from clinical specimens to antimicrobials – has traditionally occurred independently, with AST device development “often initiated following drug approval.” A coordinated approach to developing new antimicrobial drugs with AST devices ideally would minimize the time between the approval of a new antimicrobial drug and clearance of an AST device.

The FDA highlighted three key goals of the guidance document:

• Describe interactions between antimicrobial drug sponsors and AST device manufacturers to help improve coordinated development of a new antimicrobial drug and an AST device to streamline the clearance process.

• Explain the considerations for submitting separate applications to the Center for Drug Evaluation and Research and the Center for Devices and Radiological Health when seeking to facilitate clearance of an AST device as close in time as possible to antimicrobial drug approval.

• Emphasize that the review of the new antimicrobial drug product and AST device(s) will remain independent, and that coordinated development does not influence the review timelines for either product.

The FDA will accept comments and suggestions on the draft guidance document within 60 days of publication in the Federal Register.

[email protected]

On Twitter @richpizzi

The Food and Drug Administration has released a draft guidance document intended to help drug sponsors and device manufacturers coordinate the development of new antimicrobial drugs and antimicrobial susceptibility test devices (ASTs).

The FDA said it wants the guidance document, entitled “Coordinated Development of Antimicrobial Drugs and Antimicrobial Susceptibility Test Devices,” to help harmonize “development of these products such that the AST device could be cleared either at the time of new drug approval or shortly thereafter.” The agency acknowledged in the guidance document that development of antimicrobial drugs and ASTs – which test for in vitro susceptibility of bacterial pathogens isolated from clinical specimens to antimicrobials – has traditionally occurred independently, with AST device development “often initiated following drug approval.” A coordinated approach to developing new antimicrobial drugs with AST devices ideally would minimize the time between the approval of a new antimicrobial drug and clearance of an AST device.

The FDA highlighted three key goals of the guidance document:

• Describe interactions between antimicrobial drug sponsors and AST device manufacturers to help improve coordinated development of a new antimicrobial drug and an AST device to streamline the clearance process.

• Explain the considerations for submitting separate applications to the Center for Drug Evaluation and Research and the Center for Devices and Radiological Health when seeking to facilitate clearance of an AST device as close in time as possible to antimicrobial drug approval.

• Emphasize that the review of the new antimicrobial drug product and AST device(s) will remain independent, and that coordinated development does not influence the review timelines for either product.

The FDA will accept comments and suggestions on the draft guidance document within 60 days of publication in the Federal Register.

[email protected]

On Twitter @richpizzi

Antimicrobial stewardship programs are being introduced in hospitals internationally amidst the problem of escalating antimicrobial resistance. But sustained behavioral change in the area of antibiotic prescribing has been difficult to achieve.

While we have an understanding of doctors’ roles in antibiotic optimization within hospital contexts, the role of hospital management in successes or failures of antimicrobial stewardship programs (and optimization of antibiotics more broadly) has not been explored. Our new study published in the Journal of Hospital Infection examines this very question – the role of the manager as an enabler, or indeed a barrier, to antibiotic optimization.

Researchers in the study performed semistructured interviews with 23 hospital managers at three hospitals in two different states in Australia to specifically examine their opinions on antibiotic resistance, antibiotic governance, and their roles as senior management. The results illustrate how hospital managers prioritize financial pressures and immediate clinical demands over longer-term issues such as antibiotic prescribing and resistance. Here is an example of those pressures, described by one manager:

“I think the problem is [antimicrobial stewardship] in a competitive market. Are the waiting lists more newsworthy than antibiotic prescribing? Absolutely. You get more adverse events happening because of the waiting lists. … So, of course it’s not going to be the [antibiotic] prescribing that comes up to the top of that.” –Departmental Director

The study results also showed how managers find it challenging to comprehend, or act on the basis of, antibiotic-prescribing audits and had little faith in the value of data on antibiotic use and appropriateness. Other clinical areas with more clearly defined targets (and consequences for failing to meet targets) were prioritized over antibiotic prescribing in medical management decision making. Managers also found it difficult to influence the behavior of doctors and thought that it was a clinical responsibility to improve practice. In the words of one:

“I am a believer in delegated accountability and people on the shop floor knowing what they’re doing and being held accountable for it.” – Divisional Director

Managers perceived that there was limited accountability among doctors for antibiotic use and limited education and feedback to doctors:

“Those figures [on suboptimal prescribing] you give me, I haven’t heard them before. So, that in itself is a problem, and I would suggest you’d probably find a large number of medical staff haven’t been exposed to that.”

– Divisional Director

This study was performed in three hospitals with active antimicrobial stewardship programs. In Australia, as is becoming the pattern in countries within the Organisation for Economic Co-operation and Development (OECD), there is a legislative requirement for hospitals to have an effective antimicrobial stewardship program. And yet, meaningful sustained change in antibiotic prescribing is elusive, as evidenced by national antibiotic-prescribing data. The study results raise the important question of who is perceived as responsible for antibiotic-prescribing improvement and the actual and potential role of hospital managers in enacting change. It seems likely that both “top-down” influence (by managers and executive) and “bottom-up” influence (clinician-driven processes) will be required for effective and sustained practice change.

It is also clear from the results of this study that hospital managers do not perceive clear or immediate consequences for failing to improve antibiotic prescribing, and the perceived “distant” threat of antimicrobial resistance is not prioritized among other competing pressures. In addition, the widespread nature of antibiotic use makes it difficult to audit and even more difficult to communicate the extent of the problem.

These data would suggest that to move forward we need to look at an incentive structure for antibiotic-prescribing improvements or consequences in the short term for failing to optimize antibiotic use, and clearly defined goals for antibiotic optimization in hospitals.

Jennifer Broom, MBChB, PhD, is an infectious diseases physician at the Sunshine Coast Hospital and Health Service and an associate professor of medicine at the University of Queensland, Brisbane, Australia. Alex Broom, PhD, is professor of sociology in the School of Social Sciences at the University of New South Wales, Sydney.

Antimicrobial stewardship programs are being introduced in hospitals internationally amidst the problem of escalating antimicrobial resistance. But sustained behavioral change in the area of antibiotic prescribing has been difficult to achieve.

While we have an understanding of doctors’ roles in antibiotic optimization within hospital contexts, the role of hospital management in successes or failures of antimicrobial stewardship programs (and optimization of antibiotics more broadly) has not been explored. Our new study published in the Journal of Hospital Infection examines this very question – the role of the manager as an enabler, or indeed a barrier, to antibiotic optimization.

Researchers in the study performed semistructured interviews with 23 hospital managers at three hospitals in two different states in Australia to specifically examine their opinions on antibiotic resistance, antibiotic governance, and their roles as senior management. The results illustrate how hospital managers prioritize financial pressures and immediate clinical demands over longer-term issues such as antibiotic prescribing and resistance. Here is an example of those pressures, described by one manager:

“I think the problem is [antimicrobial stewardship] in a competitive market. Are the waiting lists more newsworthy than antibiotic prescribing? Absolutely. You get more adverse events happening because of the waiting lists. … So, of course it’s not going to be the [antibiotic] prescribing that comes up to the top of that.” –Departmental Director

The study results also showed how managers find it challenging to comprehend, or act on the basis of, antibiotic-prescribing audits and had little faith in the value of data on antibiotic use and appropriateness. Other clinical areas with more clearly defined targets (and consequences for failing to meet targets) were prioritized over antibiotic prescribing in medical management decision making. Managers also found it difficult to influence the behavior of doctors and thought that it was a clinical responsibility to improve practice. In the words of one:

“I am a believer in delegated accountability and people on the shop floor knowing what they’re doing and being held accountable for it.” – Divisional Director

Managers perceived that there was limited accountability among doctors for antibiotic use and limited education and feedback to doctors:

“Those figures [on suboptimal prescribing] you give me, I haven’t heard them before. So, that in itself is a problem, and I would suggest you’d probably find a large number of medical staff haven’t been exposed to that.”

– Divisional Director

This study was performed in three hospitals with active antimicrobial stewardship programs. In Australia, as is becoming the pattern in countries within the Organisation for Economic Co-operation and Development (OECD), there is a legislative requirement for hospitals to have an effective antimicrobial stewardship program. And yet, meaningful sustained change in antibiotic prescribing is elusive, as evidenced by national antibiotic-prescribing data. The study results raise the important question of who is perceived as responsible for antibiotic-prescribing improvement and the actual and potential role of hospital managers in enacting change. It seems likely that both “top-down” influence (by managers and executive) and “bottom-up” influence (clinician-driven processes) will be required for effective and sustained practice change.

It is also clear from the results of this study that hospital managers do not perceive clear or immediate consequences for failing to improve antibiotic prescribing, and the perceived “distant” threat of antimicrobial resistance is not prioritized among other competing pressures. In addition, the widespread nature of antibiotic use makes it difficult to audit and even more difficult to communicate the extent of the problem.

These data would suggest that to move forward we need to look at an incentive structure for antibiotic-prescribing improvements or consequences in the short term for failing to optimize antibiotic use, and clearly defined goals for antibiotic optimization in hospitals.

Jennifer Broom, MBChB, PhD, is an infectious diseases physician at the Sunshine Coast Hospital and Health Service and an associate professor of medicine at the University of Queensland, Brisbane, Australia. Alex Broom, PhD, is professor of sociology in the School of Social Sciences at the University of New South Wales, Sydney.

Antimicrobial stewardship programs are being introduced in hospitals internationally amidst the problem of escalating antimicrobial resistance. But sustained behavioral change in the area of antibiotic prescribing has been difficult to achieve.

While we have an understanding of doctors’ roles in antibiotic optimization within hospital contexts, the role of hospital management in successes or failures of antimicrobial stewardship programs (and optimization of antibiotics more broadly) has not been explored. Our new study published in the Journal of Hospital Infection examines this very question – the role of the manager as an enabler, or indeed a barrier, to antibiotic optimization.

Researchers in the study performed semistructured interviews with 23 hospital managers at three hospitals in two different states in Australia to specifically examine their opinions on antibiotic resistance, antibiotic governance, and their roles as senior management. The results illustrate how hospital managers prioritize financial pressures and immediate clinical demands over longer-term issues such as antibiotic prescribing and resistance. Here is an example of those pressures, described by one manager:

“I think the problem is [antimicrobial stewardship] in a competitive market. Are the waiting lists more newsworthy than antibiotic prescribing? Absolutely. You get more adverse events happening because of the waiting lists. … So, of course it’s not going to be the [antibiotic] prescribing that comes up to the top of that.” –Departmental Director

The study results also showed how managers find it challenging to comprehend, or act on the basis of, antibiotic-prescribing audits and had little faith in the value of data on antibiotic use and appropriateness. Other clinical areas with more clearly defined targets (and consequences for failing to meet targets) were prioritized over antibiotic prescribing in medical management decision making. Managers also found it difficult to influence the behavior of doctors and thought that it was a clinical responsibility to improve practice. In the words of one:

“I am a believer in delegated accountability and people on the shop floor knowing what they’re doing and being held accountable for it.” – Divisional Director

Managers perceived that there was limited accountability among doctors for antibiotic use and limited education and feedback to doctors:

“Those figures [on suboptimal prescribing] you give me, I haven’t heard them before. So, that in itself is a problem, and I would suggest you’d probably find a large number of medical staff haven’t been exposed to that.”

– Divisional Director

This study was performed in three hospitals with active antimicrobial stewardship programs. In Australia, as is becoming the pattern in countries within the Organisation for Economic Co-operation and Development (OECD), there is a legislative requirement for hospitals to have an effective antimicrobial stewardship program. And yet, meaningful sustained change in antibiotic prescribing is elusive, as evidenced by national antibiotic-prescribing data. The study results raise the important question of who is perceived as responsible for antibiotic-prescribing improvement and the actual and potential role of hospital managers in enacting change. It seems likely that both “top-down” influence (by managers and executive) and “bottom-up” influence (clinician-driven processes) will be required for effective and sustained practice change.

It is also clear from the results of this study that hospital managers do not perceive clear or immediate consequences for failing to improve antibiotic prescribing, and the perceived “distant” threat of antimicrobial resistance is not prioritized among other competing pressures. In addition, the widespread nature of antibiotic use makes it difficult to audit and even more difficult to communicate the extent of the problem.

These data would suggest that to move forward we need to look at an incentive structure for antibiotic-prescribing improvements or consequences in the short term for failing to optimize antibiotic use, and clearly defined goals for antibiotic optimization in hospitals.

Jennifer Broom, MBChB, PhD, is an infectious diseases physician at the Sunshine Coast Hospital and Health Service and an associate professor of medicine at the University of Queensland, Brisbane, Australia. Alex Broom, PhD, is professor of sociology in the School of Social Sciences at the University of New South Wales, Sydney.

About half of individuals infected with methicillin-resistant Staphylococcus aureus report feeling stigmatized in interactions with hospital staff, data from a survey of 61 adult patients show.

“Hospital care for people who carry MRSA calls for a dedicated and patient-centered approach in both the way the care is delivered ... as well as the way the care is organized at the institutional level,” wrote Babette Rump, MD, of the Regional Health Service Utrecht region, Zeist, the Netherlands, and her coauthors (J Hosp Infect. 2016. doi: 10.1016/j.jhin.2016.09.010). “Prevention of unnecessary intrusive measures, while as the same time applying appropriate precautionary measures, is key to successful and respectful MRSA management.”

Courtesy U.S. National Institute of Allergy and Infectious Diseases

Dr. Rump and her associates set out to identify and quantify stigma tied to MRSA and “explore its association with mental health within a country with a MRSA ‘search and destroy’ policy.” In the Netherlands and Scandinavian countries, this policy includes isolating MRSA carriers, wearing personal protective equipment, and disinfecting the room after patients are discharged (Antimicrob Resist Infect Control. 2014 Jan 15;3[1]3). The U.S. Centers for Disease Control and Prevention, in its 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings, recommends similar methods, including application of infection control precautions during patient care and environmental measures, such as cleaning and disinfection of the patient care environment and dedicated single-patient use of noncritical equipment.

In the current study, 60-item questionnaires were provided to all adult patients at two hospitals and two regional health services who had acquired MRSA between Oct. 1, 2013, and April 1, 2014. Stigma was assessed using the 40-item Berger HIV Stigma Scale, reported Dr. Rump.

Overall, 56% of survey respondents reported stigma, including 14% who reported clear stigma and 42% who reported suggestive stigma. The remaining 44% reported no stigma. A total of 80% of the patients received MRSA eradication treatment, which was strongly associated with higher stigma, the researchers noted.

Written comments provided by 40 patients (68%) along with the questionnaires “offer valuable insights to set the focus for improvement,” the researchers said.

The most frequent comments involved patients’ perceived organizational problems with the hospital (8 patients), lack of staff knowledge (4 patients), as well as little attention paid to patient perspectives (4 patients) and unnecessarily intrusive treatments (3 patients). Also of note, 5 patients blamed and 2 “shamed” the hospital as their source of MRSA.

The results were limited by several factors, including the small study size, the researchers wrote. However, the findings suggest that “a substantial proportion of people that carry MRSA experience signs of stigma and that anticipation on MRSA-associated stigma is warranted,” they said.

The researchers had no financial conflicts to disclose.

About half of individuals infected with methicillin-resistant Staphylococcus aureus report feeling stigmatized in interactions with hospital staff, data from a survey of 61 adult patients show.

“Hospital care for people who carry MRSA calls for a dedicated and patient-centered approach in both the way the care is delivered ... as well as the way the care is organized at the institutional level,” wrote Babette Rump, MD, of the Regional Health Service Utrecht region, Zeist, the Netherlands, and her coauthors (J Hosp Infect. 2016. doi: 10.1016/j.jhin.2016.09.010). “Prevention of unnecessary intrusive measures, while as the same time applying appropriate precautionary measures, is key to successful and respectful MRSA management.”

Courtesy U.S. National Institute of Allergy and Infectious Diseases

Dr. Rump and her associates set out to identify and quantify stigma tied to MRSA and “explore its association with mental health within a country with a MRSA ‘search and destroy’ policy.” In the Netherlands and Scandinavian countries, this policy includes isolating MRSA carriers, wearing personal protective equipment, and disinfecting the room after patients are discharged (Antimicrob Resist Infect Control. 2014 Jan 15;3[1]3). The U.S. Centers for Disease Control and Prevention, in its 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings, recommends similar methods, including application of infection control precautions during patient care and environmental measures, such as cleaning and disinfection of the patient care environment and dedicated single-patient use of noncritical equipment.

In the current study, 60-item questionnaires were provided to all adult patients at two hospitals and two regional health services who had acquired MRSA between Oct. 1, 2013, and April 1, 2014. Stigma was assessed using the 40-item Berger HIV Stigma Scale, reported Dr. Rump.

Overall, 56% of survey respondents reported stigma, including 14% who reported clear stigma and 42% who reported suggestive stigma. The remaining 44% reported no stigma. A total of 80% of the patients received MRSA eradication treatment, which was strongly associated with higher stigma, the researchers noted.

Written comments provided by 40 patients (68%) along with the questionnaires “offer valuable insights to set the focus for improvement,” the researchers said.

The most frequent comments involved patients’ perceived organizational problems with the hospital (8 patients), lack of staff knowledge (4 patients), as well as little attention paid to patient perspectives (4 patients) and unnecessarily intrusive treatments (3 patients). Also of note, 5 patients blamed and 2 “shamed” the hospital as their source of MRSA.

The results were limited by several factors, including the small study size, the researchers wrote. However, the findings suggest that “a substantial proportion of people that carry MRSA experience signs of stigma and that anticipation on MRSA-associated stigma is warranted,” they said.

The researchers had no financial conflicts to disclose.

About half of individuals infected with methicillin-resistant Staphylococcus aureus report feeling stigmatized in interactions with hospital staff, data from a survey of 61 adult patients show.

“Hospital care for people who carry MRSA calls for a dedicated and patient-centered approach in both the way the care is delivered ... as well as the way the care is organized at the institutional level,” wrote Babette Rump, MD, of the Regional Health Service Utrecht region, Zeist, the Netherlands, and her coauthors (J Hosp Infect. 2016. doi: 10.1016/j.jhin.2016.09.010). “Prevention of unnecessary intrusive measures, while as the same time applying appropriate precautionary measures, is key to successful and respectful MRSA management.”

Courtesy U.S. National Institute of Allergy and Infectious Diseases

Dr. Rump and her associates set out to identify and quantify stigma tied to MRSA and “explore its association with mental health within a country with a MRSA ‘search and destroy’ policy.” In the Netherlands and Scandinavian countries, this policy includes isolating MRSA carriers, wearing personal protective equipment, and disinfecting the room after patients are discharged (Antimicrob Resist Infect Control. 2014 Jan 15;3[1]3). The U.S. Centers for Disease Control and Prevention, in its 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings, recommends similar methods, including application of infection control precautions during patient care and environmental measures, such as cleaning and disinfection of the patient care environment and dedicated single-patient use of noncritical equipment.

In the current study, 60-item questionnaires were provided to all adult patients at two hospitals and two regional health services who had acquired MRSA between Oct. 1, 2013, and April 1, 2014. Stigma was assessed using the 40-item Berger HIV Stigma Scale, reported Dr. Rump.

Overall, 56% of survey respondents reported stigma, including 14% who reported clear stigma and 42% who reported suggestive stigma. The remaining 44% reported no stigma. A total of 80% of the patients received MRSA eradication treatment, which was strongly associated with higher stigma, the researchers noted.

Written comments provided by 40 patients (68%) along with the questionnaires “offer valuable insights to set the focus for improvement,” the researchers said.

The most frequent comments involved patients’ perceived organizational problems with the hospital (8 patients), lack of staff knowledge (4 patients), as well as little attention paid to patient perspectives (4 patients) and unnecessarily intrusive treatments (3 patients). Also of note, 5 patients blamed and 2 “shamed” the hospital as their source of MRSA.

The results were limited by several factors, including the small study size, the researchers wrote. However, the findings suggest that “a substantial proportion of people that carry MRSA experience signs of stigma and that anticipation on MRSA-associated stigma is warranted,” they said.

The researchers had no financial conflicts to disclose.

ATLANTA – A cluster of gonorrhea cases from the state of Hawaii has been identified as the first in the United States to show decreased susceptibility to ceftriaxone and azithromycin, the two most commonly prescribed drugs used to treat the infection.

“We’re seeing new, troubling signs that our current gonorrhea treatment is losing its effectiveness [but] we’ve not seen a treatment failure in the U.S.,” explained Jonathan Mermin, MD, director of the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, during a conference on STD prevention sponsored by the Centers for Disease Control and Prevention.

Isolates were collected from seven individuals in Hawaii during April and May of this year, all of which showed “dramatically higher levels” of resistance to azithromycin in laboratory testing than has normally been seen in the U.S. While large-scale resistance to azithromycin is something the CDC has watched for several months, four of these seven isolates also demonstrated less vulnerability to ceftriaxone, the first time that has occurred. Since 2010, the recommended treatment for gonorrhea has consisted of a single ceftriaxone shot and an oral dose of azithromycin; having a cluster with increased resistance to both is problematic on several levels, infectious disease experts say.

According to Alan Katz, MD, of the University of Hawaii in Honolulu, “the state of Hawaii has been a seminal site for monitoring Neisseria gonorrhoeae resistance, and the Hawaii state Department of Health has been one of the original CDC gonococcal isolate surveillance program surveillance sites since its inception in 1986.” Hawaii typically sees more gonorrhea cases than the rest of the country, partially due its location between the U.S. and Asia, the latter of which Dr. Katz explained is “where we believe many [drug]-resistant strains originate.”

Currently, trials are underway to identify a new treatment that can replace the current regimen, with promising early results. The drug in question, known as ETX0914, is a single-dose oral therapy that would substitute for ceftriaxone in the currently recommended treatment protocol. Stephanie N. Taylor, MD, of Louisiana State University in New Orleans, shared results of a randomized controlled trial, in which 179 subjects – 167 males and 12 females – received either 2g or 3g doses of only ETX0914, or only ceftriaxone.

A total of 47 subjects received the 3g ETX0914 dose, while 49 subjects received the 2g dose, and the rest received ceftriaxone. All patients (47/47) receiving the 3g dose were cured, and 98% (48/49) in the 2g dose were cured, with only 21 subjects (12%) in the entire study population reporting mild side effects.

“We are very pleased with these results and look forward to seeing ETX0914 advance through additional clinical trials,” Dr. Taylor said in a statement.

For now, health care providers are encouraged to continue with the currently recommended drug therapy, which is still effective. In a statement, Gail Bolan, MD, director of the Division of STD Prevention at the CDC, reminded providers that infections should be treated immediately in order for the drugs to have their full impact.

“All health care providers should also promptly report any suspected treatment failure to local health officials and CDC to ensure rapid response to cases or clusters of concern,” she added.

[email protected]

ATLANTA – A cluster of gonorrhea cases from the state of Hawaii has been identified as the first in the United States to show decreased susceptibility to ceftriaxone and azithromycin, the two most commonly prescribed drugs used to treat the infection.

“We’re seeing new, troubling signs that our current gonorrhea treatment is losing its effectiveness [but] we’ve not seen a treatment failure in the U.S.,” explained Jonathan Mermin, MD, director of the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, during a conference on STD prevention sponsored by the Centers for Disease Control and Prevention.

Isolates were collected from seven individuals in Hawaii during April and May of this year, all of which showed “dramatically higher levels” of resistance to azithromycin in laboratory testing than has normally been seen in the U.S. While large-scale resistance to azithromycin is something the CDC has watched for several months, four of these seven isolates also demonstrated less vulnerability to ceftriaxone, the first time that has occurred. Since 2010, the recommended treatment for gonorrhea has consisted of a single ceftriaxone shot and an oral dose of azithromycin; having a cluster with increased resistance to both is problematic on several levels, infectious disease experts say.

According to Alan Katz, MD, of the University of Hawaii in Honolulu, “the state of Hawaii has been a seminal site for monitoring Neisseria gonorrhoeae resistance, and the Hawaii state Department of Health has been one of the original CDC gonococcal isolate surveillance program surveillance sites since its inception in 1986.” Hawaii typically sees more gonorrhea cases than the rest of the country, partially due its location between the U.S. and Asia, the latter of which Dr. Katz explained is “where we believe many [drug]-resistant strains originate.”

Currently, trials are underway to identify a new treatment that can replace the current regimen, with promising early results. The drug in question, known as ETX0914, is a single-dose oral therapy that would substitute for ceftriaxone in the currently recommended treatment protocol. Stephanie N. Taylor, MD, of Louisiana State University in New Orleans, shared results of a randomized controlled trial, in which 179 subjects – 167 males and 12 females – received either 2g or 3g doses of only ETX0914, or only ceftriaxone.

A total of 47 subjects received the 3g ETX0914 dose, while 49 subjects received the 2g dose, and the rest received ceftriaxone. All patients (47/47) receiving the 3g dose were cured, and 98% (48/49) in the 2g dose were cured, with only 21 subjects (12%) in the entire study population reporting mild side effects.

“We are very pleased with these results and look forward to seeing ETX0914 advance through additional clinical trials,” Dr. Taylor said in a statement.

For now, health care providers are encouraged to continue with the currently recommended drug therapy, which is still effective. In a statement, Gail Bolan, MD, director of the Division of STD Prevention at the CDC, reminded providers that infections should be treated immediately in order for the drugs to have their full impact.

“All health care providers should also promptly report any suspected treatment failure to local health officials and CDC to ensure rapid response to cases or clusters of concern,” she added.

[email protected]

ATLANTA – A cluster of gonorrhea cases from the state of Hawaii has been identified as the first in the United States to show decreased susceptibility to ceftriaxone and azithromycin, the two most commonly prescribed drugs used to treat the infection.

“We’re seeing new, troubling signs that our current gonorrhea treatment is losing its effectiveness [but] we’ve not seen a treatment failure in the U.S.,” explained Jonathan Mermin, MD, director of the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, during a conference on STD prevention sponsored by the Centers for Disease Control and Prevention.

Isolates were collected from seven individuals in Hawaii during April and May of this year, all of which showed “dramatically higher levels” of resistance to azithromycin in laboratory testing than has normally been seen in the U.S. While large-scale resistance to azithromycin is something the CDC has watched for several months, four of these seven isolates also demonstrated less vulnerability to ceftriaxone, the first time that has occurred. Since 2010, the recommended treatment for gonorrhea has consisted of a single ceftriaxone shot and an oral dose of azithromycin; having a cluster with increased resistance to both is problematic on several levels, infectious disease experts say.

According to Alan Katz, MD, of the University of Hawaii in Honolulu, “the state of Hawaii has been a seminal site for monitoring Neisseria gonorrhoeae resistance, and the Hawaii state Department of Health has been one of the original CDC gonococcal isolate surveillance program surveillance sites since its inception in 1986.” Hawaii typically sees more gonorrhea cases than the rest of the country, partially due its location between the U.S. and Asia, the latter of which Dr. Katz explained is “where we believe many [drug]-resistant strains originate.”

Currently, trials are underway to identify a new treatment that can replace the current regimen, with promising early results. The drug in question, known as ETX0914, is a single-dose oral therapy that would substitute for ceftriaxone in the currently recommended treatment protocol. Stephanie N. Taylor, MD, of Louisiana State University in New Orleans, shared results of a randomized controlled trial, in which 179 subjects – 167 males and 12 females – received either 2g or 3g doses of only ETX0914, or only ceftriaxone.

A total of 47 subjects received the 3g ETX0914 dose, while 49 subjects received the 2g dose, and the rest received ceftriaxone. All patients (47/47) receiving the 3g dose were cured, and 98% (48/49) in the 2g dose were cured, with only 21 subjects (12%) in the entire study population reporting mild side effects.

“We are very pleased with these results and look forward to seeing ETX0914 advance through additional clinical trials,” Dr. Taylor said in a statement.

For now, health care providers are encouraged to continue with the currently recommended drug therapy, which is still effective. In a statement, Gail Bolan, MD, director of the Division of STD Prevention at the CDC, reminded providers that infections should be treated immediately in order for the drugs to have their full impact.

“All health care providers should also promptly report any suspected treatment failure to local health officials and CDC to ensure rapid response to cases or clusters of concern,” she added.

[email protected]

Sepsis is the primary cause of death from infection. Early identification and treatment of sepsis is important in improving patient outcomes. The consensus conference sought to differentiate sepsis, which is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection” from uncomplicated infection.

Sepsis was last classified in a 2001 guideline that based its definition on the presence of two or more systemic inflammatory response syndrome (SIRS) criteria, which included an elevated temperature, heart rate higher than 90 bpm, respiratory rate higher than 20 breaths per minute, and a white blood cell count greater than greater than 12,000 mcL or less than 4,000 mcL or greater than 10% immature bands.

The problem with the SIRS definition of sepsis is that while it reflects a response to infection, it does not sufficiently distinguish between individuals with infections and those with a dysregulated response that leads to a poor prognosis, which is the definition of sepsis. The current consensus conference redefines sepsis with a more direct emphasis on organ dysfunction, as this is the aspect of sepsis that is most clearly linked to patient outcomes.

In the consensus conference document, sepsis is defined as a “life-threatening organ dysfunction caused by a dysregulated host response to infection.” The guidelines recommend using the quick version of the sequential (sepsis-related) organ failure assessment score (qSOFA) to identify patients with sepsis. In its long form, the SOFA used seven clinical and laboratory data points for completion, and is best suited to use in an intensive care setting where detailed data are available. The qSOFA score has only three criteria and by being easier to use can aid in rapid identification of sepsis and the patients most likely to deteriorate from sepsis.

The qSOFA criteria predict poor outcome in patients with infection who have two or more of the following: respiratory rate greater than or equal to 22 breaths/min, new or worsened altered mentation, or systolic blood pressure less than or equal to 100 mm Hg. Unlike the full SOFA score, the qSOFA does not require any laboratory testing and so can be performed in the office or bedside on a hospital floor. The qSOFA does not necessarily define sepsis, rather it identifies patients at a higher risk of hospital death or prolonged ICU stay. The consensus conference suggests that “qSOFA criteria be used to prompt clinicians to further investigate for organ dysfunction, initiate or escalate therapy as appropriate, and consider referral to critical care or increase the frequency of monitoring, if such actions have not already been undertaken.” The task force suggested that the qSOFA score may be a helpful adjunct to best clinical judgment for identifying patients who might benefit from a higher level of care.

Septic shock is defined as a subset of sepsis in which profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk for death than sepsis alone. Septic shock can be identified when, after adequate fluid resuscitation, the patient requires vasopressor therapy to maintain mean arterial pressure of at least 65 mm Hg and has a serum lactate level greater than 2 mmol/L.

Once sepsis is suspected, prompt therapy needs to be started as per the Surviving Sepsis Campaign Guidelines. The qSOFA criteria can be used to identify patients at high risk for morbidity and mortality. Within 3 hours, a lactate level should be obtained as well as blood cultures from two separate sites drawn prior to administration of antibiotics (but do not delay antibiotic administration). Empiric broad-spectrum antibiotics should be given within 45 minutes of the identification of sepsis. Antibiotic choice will vary per clinician/institution preference, but should likely include coverage for Pseudomonas and MRSA (piperacillin/tazobactam and vancomycin, for example). Antibiotics should be reassessed daily for de-escalation. Administer 30 mL/kg crystalloid for hypotension or lactate greater than or equal to 4 mmol/L. Within 6 hours, vasopressors should be given for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure (MAP) of at least 65mm Hg. In the event of persistent hypotension after initial fluid administration (MAP under 65 mm Hg) or if initial lactate was greater than or equal to 4 mmol/L, volume status and tissue perfusion should be reassessed and lactate should be rechecked if it was initially elevated.

The bottom line

A 2016 international task force recommended that the definition of sepsis should be changed to emphasize organ dysfunction rather than a systemic inflammatory response. Use of the qSOFA score, which relies only on clinically observable data rather than laboratory evaluation, is recommended to identify patients at high risk for morbidity and mortality. Early recognition of sepsis and evaluation with qSOFT should facilitate early treatment and improve survival.

References

Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) FRCP; JAMA. 2016;315[8]:801-10. doi: 10.1001/jama.2016.0287.

Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250-6.

Singer M, Deutschman CS, Seymour C, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016 Feb 23;315(8):801-10.

Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004 Mar;32(3):858-73.

Dr. Mills is assistant residency program director and assistant professor in the department of family and community medicine and department of physiology at Sidney Kimmel Medical College at Thomas Jefferson University. Dr. Botti is a second-year resident in the family medicine residency program department of family and community medicine at Sidney Kimmel Medical College at Thomas Jefferson University. Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia.

Sepsis is the primary cause of death from infection. Early identification and treatment of sepsis is important in improving patient outcomes. The consensus conference sought to differentiate sepsis, which is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection” from uncomplicated infection.

Sepsis was last classified in a 2001 guideline that based its definition on the presence of two or more systemic inflammatory response syndrome (SIRS) criteria, which included an elevated temperature, heart rate higher than 90 bpm, respiratory rate higher than 20 breaths per minute, and a white blood cell count greater than greater than 12,000 mcL or less than 4,000 mcL or greater than 10% immature bands.

The problem with the SIRS definition of sepsis is that while it reflects a response to infection, it does not sufficiently distinguish between individuals with infections and those with a dysregulated response that leads to a poor prognosis, which is the definition of sepsis. The current consensus conference redefines sepsis with a more direct emphasis on organ dysfunction, as this is the aspect of sepsis that is most clearly linked to patient outcomes.

In the consensus conference document, sepsis is defined as a “life-threatening organ dysfunction caused by a dysregulated host response to infection.” The guidelines recommend using the quick version of the sequential (sepsis-related) organ failure assessment score (qSOFA) to identify patients with sepsis. In its long form, the SOFA used seven clinical and laboratory data points for completion, and is best suited to use in an intensive care setting where detailed data are available. The qSOFA score has only three criteria and by being easier to use can aid in rapid identification of sepsis and the patients most likely to deteriorate from sepsis.

The qSOFA criteria predict poor outcome in patients with infection who have two or more of the following: respiratory rate greater than or equal to 22 breaths/min, new or worsened altered mentation, or systolic blood pressure less than or equal to 100 mm Hg. Unlike the full SOFA score, the qSOFA does not require any laboratory testing and so can be performed in the office or bedside on a hospital floor. The qSOFA does not necessarily define sepsis, rather it identifies patients at a higher risk of hospital death or prolonged ICU stay. The consensus conference suggests that “qSOFA criteria be used to prompt clinicians to further investigate for organ dysfunction, initiate or escalate therapy as appropriate, and consider referral to critical care or increase the frequency of monitoring, if such actions have not already been undertaken.” The task force suggested that the qSOFA score may be a helpful adjunct to best clinical judgment for identifying patients who might benefit from a higher level of care.

Septic shock is defined as a subset of sepsis in which profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk for death than sepsis alone. Septic shock can be identified when, after adequate fluid resuscitation, the patient requires vasopressor therapy to maintain mean arterial pressure of at least 65 mm Hg and has a serum lactate level greater than 2 mmol/L.

Once sepsis is suspected, prompt therapy needs to be started as per the Surviving Sepsis Campaign Guidelines. The qSOFA criteria can be used to identify patients at high risk for morbidity and mortality. Within 3 hours, a lactate level should be obtained as well as blood cultures from two separate sites drawn prior to administration of antibiotics (but do not delay antibiotic administration). Empiric broad-spectrum antibiotics should be given within 45 minutes of the identification of sepsis. Antibiotic choice will vary per clinician/institution preference, but should likely include coverage for Pseudomonas and MRSA (piperacillin/tazobactam and vancomycin, for example). Antibiotics should be reassessed daily for de-escalation. Administer 30 mL/kg crystalloid for hypotension or lactate greater than or equal to 4 mmol/L. Within 6 hours, vasopressors should be given for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure (MAP) of at least 65mm Hg. In the event of persistent hypotension after initial fluid administration (MAP under 65 mm Hg) or if initial lactate was greater than or equal to 4 mmol/L, volume status and tissue perfusion should be reassessed and lactate should be rechecked if it was initially elevated.

The bottom line

A 2016 international task force recommended that the definition of sepsis should be changed to emphasize organ dysfunction rather than a systemic inflammatory response. Use of the qSOFA score, which relies only on clinically observable data rather than laboratory evaluation, is recommended to identify patients at high risk for morbidity and mortality. Early recognition of sepsis and evaluation with qSOFT should facilitate early treatment and improve survival.

References

Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) FRCP; JAMA. 2016;315[8]:801-10. doi: 10.1001/jama.2016.0287.

Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250-6.

Singer M, Deutschman CS, Seymour C, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016 Feb 23;315(8):801-10.

Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004 Mar;32(3):858-73.

Dr. Mills is assistant residency program director and assistant professor in the department of family and community medicine and department of physiology at Sidney Kimmel Medical College at Thomas Jefferson University. Dr. Botti is a second-year resident in the family medicine residency program department of family and community medicine at Sidney Kimmel Medical College at Thomas Jefferson University. Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia.

Sepsis is the primary cause of death from infection. Early identification and treatment of sepsis is important in improving patient outcomes. The consensus conference sought to differentiate sepsis, which is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection” from uncomplicated infection.

Sepsis was last classified in a 2001 guideline that based its definition on the presence of two or more systemic inflammatory response syndrome (SIRS) criteria, which included an elevated temperature, heart rate higher than 90 bpm, respiratory rate higher than 20 breaths per minute, and a white blood cell count greater than greater than 12,000 mcL or less than 4,000 mcL or greater than 10% immature bands.

The problem with the SIRS definition of sepsis is that while it reflects a response to infection, it does not sufficiently distinguish between individuals with infections and those with a dysregulated response that leads to a poor prognosis, which is the definition of sepsis. The current consensus conference redefines sepsis with a more direct emphasis on organ dysfunction, as this is the aspect of sepsis that is most clearly linked to patient outcomes.

In the consensus conference document, sepsis is defined as a “life-threatening organ dysfunction caused by a dysregulated host response to infection.” The guidelines recommend using the quick version of the sequential (sepsis-related) organ failure assessment score (qSOFA) to identify patients with sepsis. In its long form, the SOFA used seven clinical and laboratory data points for completion, and is best suited to use in an intensive care setting where detailed data are available. The qSOFA score has only three criteria and by being easier to use can aid in rapid identification of sepsis and the patients most likely to deteriorate from sepsis.

The qSOFA criteria predict poor outcome in patients with infection who have two or more of the following: respiratory rate greater than or equal to 22 breaths/min, new or worsened altered mentation, or systolic blood pressure less than or equal to 100 mm Hg. Unlike the full SOFA score, the qSOFA does not require any laboratory testing and so can be performed in the office or bedside on a hospital floor. The qSOFA does not necessarily define sepsis, rather it identifies patients at a higher risk of hospital death or prolonged ICU stay. The consensus conference suggests that “qSOFA criteria be used to prompt clinicians to further investigate for organ dysfunction, initiate or escalate therapy as appropriate, and consider referral to critical care or increase the frequency of monitoring, if such actions have not already been undertaken.” The task force suggested that the qSOFA score may be a helpful adjunct to best clinical judgment for identifying patients who might benefit from a higher level of care.

Septic shock is defined as a subset of sepsis in which profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk for death than sepsis alone. Septic shock can be identified when, after adequate fluid resuscitation, the patient requires vasopressor therapy to maintain mean arterial pressure of at least 65 mm Hg and has a serum lactate level greater than 2 mmol/L.

Once sepsis is suspected, prompt therapy needs to be started as per the Surviving Sepsis Campaign Guidelines. The qSOFA criteria can be used to identify patients at high risk for morbidity and mortality. Within 3 hours, a lactate level should be obtained as well as blood cultures from two separate sites drawn prior to administration of antibiotics (but do not delay antibiotic administration). Empiric broad-spectrum antibiotics should be given within 45 minutes of the identification of sepsis. Antibiotic choice will vary per clinician/institution preference, but should likely include coverage for Pseudomonas and MRSA (piperacillin/tazobactam and vancomycin, for example). Antibiotics should be reassessed daily for de-escalation. Administer 30 mL/kg crystalloid for hypotension or lactate greater than or equal to 4 mmol/L. Within 6 hours, vasopressors should be given for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure (MAP) of at least 65mm Hg. In the event of persistent hypotension after initial fluid administration (MAP under 65 mm Hg) or if initial lactate was greater than or equal to 4 mmol/L, volume status and tissue perfusion should be reassessed and lactate should be rechecked if it was initially elevated.

The bottom line

A 2016 international task force recommended that the definition of sepsis should be changed to emphasize organ dysfunction rather than a systemic inflammatory response. Use of the qSOFA score, which relies only on clinically observable data rather than laboratory evaluation, is recommended to identify patients at high risk for morbidity and mortality. Early recognition of sepsis and evaluation with qSOFT should facilitate early treatment and improve survival.

References

Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) FRCP; JAMA. 2016;315[8]:801-10. doi: 10.1001/jama.2016.0287.

Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250-6.

Singer M, Deutschman CS, Seymour C, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016 Feb 23;315(8):801-10.

Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004 Mar;32(3):858-73.

Dr. Mills is assistant residency program director and assistant professor in the department of family and community medicine and department of physiology at Sidney Kimmel Medical College at Thomas Jefferson University. Dr. Botti is a second-year resident in the family medicine residency program department of family and community medicine at Sidney Kimmel Medical College at Thomas Jefferson University. Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia.

Primary care practitioners’ use of a seven-item checklist may reduce the number of pediatric patients with respiratory tract infections who are prescribed unnecessary antibiotics, a prognostic cohort study suggests.

The study revealed short illness (a duration of illness of 3 days or less), temperature (a body temperature of 37.8°C or greater at presentation), age (being under 2 years), intercostal or subcostal recession, wheeze on auscultation, asthma, and vomiting (moderate or severe in the previous 24 hours) were each independently associated with hospital admission (P less than .01 for all associations).

©Devonyu/thinkstockphotos.com

The checklist includes these seven characteristics or risk variables (short illness, temperature, age, recession, wheeze, asthma, and vomiting [mnemonic STARWAVe]). To use the checklist, a primary care practitioner would assign one point for the presence of each item in a patient then add up all of the points to determine that patient’s risk level for future hospital admission for respiratory tract infection. A score of 1 point or less, observed in 5,593 (67%) cases would be considered indicative of a very low rate of risk for hospitalization (0.3%, 0.2%-0.4%). A score of 2 or 3 points, found for 2,520 (30%) children, would be considered as a normal level of risk (1.5%, 1.0%-1.9%), and a score of 4 or more points, seen in 204 (3%) children, would signify a high risk level (11.8%, 7.3%-16.2%).

Of the 8,394 children assessed, 78 (0.9%; 95% confidence interval, 0.7%-1.2%) were admitted to a hospital. Most were admitted on days 2-7 (33, 42%) and on days 8-30 (30, 39%) following recruitment. Only 15 (19%) were admitted on the day of recruitment (day 1).

“Many clinicians report that they prescribe antibiotics just in case, to mitigate perceived risk of future hospital admission and complications, and that failing to provide a prescription for a child who subsequently becomes seriously unwell is professionally unacceptable. If primary care clinicians could identify children at low (or very low) risk of such future complications, the reduced clinical uncertainty could lead to a reduced use of antibiotics in these groups of patients,” wrote first author Alastair Hay, MD, from the Centre for Academic Primary Care in the School of Social and Community Medicine at the University of Bristol (England), and his colleagues.

These researchers conducted the study based on a structured, blinded review of the medical records from children aged between 3 months and 16 years presenting with acute cough (less than or equal to 28 days) and respiratory tract infection treated by 519 general practitioners in 247 practices in England between July 2011 and June 2013. The primary study outcome was hospital admission for respiratory tract infection within 30 days.

Additionally, a multivariable model was employed to detect factors associated with increased risk of hospital admission. As measured by receiver operating characteristic curve analysis, the accuracy of the STARWAVe score checklist in predicting risk groups and associated risk of hospitalization was found to be high (0.81; 95% CI, 0.77-0.86). The suggested probability of hospital admission for children who did not have any of the seven characteristics included in the checklist was found to be exceptionally low (0.14%).

Significantly associated parent-reported variables included both moderate or severe vomiting and severe fever, each in the previous 24 hours. Significant clinician-reported variables included intercostal or subcostal recession and wheeze on auscultation.

“The main value of our results is to reduce clinical uncertainty and antibiotic use in children least likely to benefit from them, namely those at very low risk of future hospital admission,” Dr. Hay and his associates noted in The Lancet Respiratory Medicine (Lancet Respir Med. 2016 Sep 1. doi: 10.1016/S2213-2600(16)30223-5).

Funding for this study was provided by the National Institute for Health Research and sponsored by the University of Bristol. Only one of the study’s authors, Dr. Peter Muir, reported ties to industry sources.

Primary care practitioners’ use of a seven-item checklist may reduce the number of pediatric patients with respiratory tract infections who are prescribed unnecessary antibiotics, a prognostic cohort study suggests.

The study revealed short illness (a duration of illness of 3 days or less), temperature (a body temperature of 37.8°C or greater at presentation), age (being under 2 years), intercostal or subcostal recession, wheeze on auscultation, asthma, and vomiting (moderate or severe in the previous 24 hours) were each independently associated with hospital admission (P less than .01 for all associations).

©Devonyu/thinkstockphotos.com

The checklist includes these seven characteristics or risk variables (short illness, temperature, age, recession, wheeze, asthma, and vomiting [mnemonic STARWAVe]). To use the checklist, a primary care practitioner would assign one point for the presence of each item in a patient then add up all of the points to determine that patient’s risk level for future hospital admission for respiratory tract infection. A score of 1 point or less, observed in 5,593 (67%) cases would be considered indicative of a very low rate of risk for hospitalization (0.3%, 0.2%-0.4%). A score of 2 or 3 points, found for 2,520 (30%) children, would be considered as a normal level of risk (1.5%, 1.0%-1.9%), and a score of 4 or more points, seen in 204 (3%) children, would signify a high risk level (11.8%, 7.3%-16.2%).

Of the 8,394 children assessed, 78 (0.9%; 95% confidence interval, 0.7%-1.2%) were admitted to a hospital. Most were admitted on days 2-7 (33, 42%) and on days 8-30 (30, 39%) following recruitment. Only 15 (19%) were admitted on the day of recruitment (day 1).

“Many clinicians report that they prescribe antibiotics just in case, to mitigate perceived risk of future hospital admission and complications, and that failing to provide a prescription for a child who subsequently becomes seriously unwell is professionally unacceptable. If primary care clinicians could identify children at low (or very low) risk of such future complications, the reduced clinical uncertainty could lead to a reduced use of antibiotics in these groups of patients,” wrote first author Alastair Hay, MD, from the Centre for Academic Primary Care in the School of Social and Community Medicine at the University of Bristol (England), and his colleagues.

These researchers conducted the study based on a structured, blinded review of the medical records from children aged between 3 months and 16 years presenting with acute cough (less than or equal to 28 days) and respiratory tract infection treated by 519 general practitioners in 247 practices in England between July 2011 and June 2013. The primary study outcome was hospital admission for respiratory tract infection within 30 days.

Additionally, a multivariable model was employed to detect factors associated with increased risk of hospital admission. As measured by receiver operating characteristic curve analysis, the accuracy of the STARWAVe score checklist in predicting risk groups and associated risk of hospitalization was found to be high (0.81; 95% CI, 0.77-0.86). The suggested probability of hospital admission for children who did not have any of the seven characteristics included in the checklist was found to be exceptionally low (0.14%).

Significantly associated parent-reported variables included both moderate or severe vomiting and severe fever, each in the previous 24 hours. Significant clinician-reported variables included intercostal or subcostal recession and wheeze on auscultation.

“The main value of our results is to reduce clinical uncertainty and antibiotic use in children least likely to benefit from them, namely those at very low risk of future hospital admission,” Dr. Hay and his associates noted in The Lancet Respiratory Medicine (Lancet Respir Med. 2016 Sep 1. doi: 10.1016/S2213-2600(16)30223-5).

Funding for this study was provided by the National Institute for Health Research and sponsored by the University of Bristol. Only one of the study’s authors, Dr. Peter Muir, reported ties to industry sources.

Primary care practitioners’ use of a seven-item checklist may reduce the number of pediatric patients with respiratory tract infections who are prescribed unnecessary antibiotics, a prognostic cohort study suggests.

The study revealed short illness (a duration of illness of 3 days or less), temperature (a body temperature of 37.8°C or greater at presentation), age (being under 2 years), intercostal or subcostal recession, wheeze on auscultation, asthma, and vomiting (moderate or severe in the previous 24 hours) were each independently associated with hospital admission (P less than .01 for all associations).

©Devonyu/thinkstockphotos.com

The checklist includes these seven characteristics or risk variables (short illness, temperature, age, recession, wheeze, asthma, and vomiting [mnemonic STARWAVe]). To use the checklist, a primary care practitioner would assign one point for the presence of each item in a patient then add up all of the points to determine that patient’s risk level for future hospital admission for respiratory tract infection. A score of 1 point or less, observed in 5,593 (67%) cases would be considered indicative of a very low rate of risk for hospitalization (0.3%, 0.2%-0.4%). A score of 2 or 3 points, found for 2,520 (30%) children, would be considered as a normal level of risk (1.5%, 1.0%-1.9%), and a score of 4 or more points, seen in 204 (3%) children, would signify a high risk level (11.8%, 7.3%-16.2%).

Of the 8,394 children assessed, 78 (0.9%; 95% confidence interval, 0.7%-1.2%) were admitted to a hospital. Most were admitted on days 2-7 (33, 42%) and on days 8-30 (30, 39%) following recruitment. Only 15 (19%) were admitted on the day of recruitment (day 1).

“Many clinicians report that they prescribe antibiotics just in case, to mitigate perceived risk of future hospital admission and complications, and that failing to provide a prescription for a child who subsequently becomes seriously unwell is professionally unacceptable. If primary care clinicians could identify children at low (or very low) risk of such future complications, the reduced clinical uncertainty could lead to a reduced use of antibiotics in these groups of patients,” wrote first author Alastair Hay, MD, from the Centre for Academic Primary Care in the School of Social and Community Medicine at the University of Bristol (England), and his colleagues.

These researchers conducted the study based on a structured, blinded review of the medical records from children aged between 3 months and 16 years presenting with acute cough (less than or equal to 28 days) and respiratory tract infection treated by 519 general practitioners in 247 practices in England between July 2011 and June 2013. The primary study outcome was hospital admission for respiratory tract infection within 30 days.

Additionally, a multivariable model was employed to detect factors associated with increased risk of hospital admission. As measured by receiver operating characteristic curve analysis, the accuracy of the STARWAVe score checklist in predicting risk groups and associated risk of hospitalization was found to be high (0.81; 95% CI, 0.77-0.86). The suggested probability of hospital admission for children who did not have any of the seven characteristics included in the checklist was found to be exceptionally low (0.14%).

Significantly associated parent-reported variables included both moderate or severe vomiting and severe fever, each in the previous 24 hours. Significant clinician-reported variables included intercostal or subcostal recession and wheeze on auscultation.

“The main value of our results is to reduce clinical uncertainty and antibiotic use in children least likely to benefit from them, namely those at very low risk of future hospital admission,” Dr. Hay and his associates noted in The Lancet Respiratory Medicine (Lancet Respir Med. 2016 Sep 1. doi: 10.1016/S2213-2600(16)30223-5).

Funding for this study was provided by the National Institute for Health Research and sponsored by the University of Bristol. Only one of the study’s authors, Dr. Peter Muir, reported ties to industry sources.

ANNAPOLIS, MD. – Three novel treatments for gonorrhea, currently in late stages of development, could give clinicians an edge in the fight against antibacterial resistance, according to a federal health official.

The pathogen Neisseria gonorrhoeae is already showing signs of besting first-line therapy ceftriaxone in Japan and parts of Europe, said Carolyn Deal, PhD, chief of the sexually transmitted diseases branch at the National Institute of Allergy and Infectious Diseases (NIAID). And the Centers for Disease Control and Prevention lists N. gonorrhoeae among its “urgent” antibiotic resistance threats.

“I think we have a new superbug,” Dr. Deal said at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology. “In my opinion, it’s just a matter of time in this country.”

But three agents in late-stage clinical trials for uncomplicated urogenital gonorrhea offer promise in fighting the gram-negative bacteria, according to Dr. Deal. The first is solithromycin, manufactured by Cempra. The company has a phase III study underway to compare a single dose of oral solithromycin with intramuscular ceftriaxone plus oral azithromycin for urogenital gonorrhea.

The other two drugs are first-in-class antibacterial agents. In partnership with the NIAID, the company Entasis recently completed a phase II study of zoliflodacin, an oral agent in a novel class of topoisomerase inhibitors. A phase III trial is expected to begin in 2017, also in partnership with the NIAID, according to an Entasis document. The third agent is gepotidacin, a novel triazaacenaphthylene antibacterial agent currently being investigated by GlaxoSmithKline in a phase II study.

Centers for Disease Control and Prevention

Because N. gonorrhoeae poses such an urgent threat, waiting to develop a vaccine is less feasible than working with companies to develop additional antibacterial agents, Dr. Deal said. But taking a compound out of the basic research lab and having enough data to get into the investigational new drug phase is a significant investment, she said, so pharmaceutical manufacturers look for as many indications for a drug as possible.

For instance, solithromycin was initially investigated for community-acquired pneumonia. Gepotidacin initially was developed in partnership with the NIAID and the Biomedical Advanced Research and Development Authority in case of an anthrax attack, Dr. Deal said. “The Entasis product is the only one specifically developed for Neisseria gonorrhoeae,” she said.

One reason that two of the drugs in the pipeline include N. gonorrhoeae as an indication is that the Food and Drug Administration has issued guidance on developing drugs in the area of uncomplicated gonorrhea. That guidance is lacking for nasopharyngeal and rectal gonorrhea, leaving a “vacuum” in the pipeline, Dr. Deal said. “Many of us have come to the conclusion that developing vaccines is the only real long-term solution.”

[email protected]

On Twitter @whitneymcknight

ANNAPOLIS, MD. – Three novel treatments for gonorrhea, currently in late stages of development, could give clinicians an edge in the fight against antibacterial resistance, according to a federal health official.

The pathogen Neisseria gonorrhoeae is already showing signs of besting first-line therapy ceftriaxone in Japan and parts of Europe, said Carolyn Deal, PhD, chief of the sexually transmitted diseases branch at the National Institute of Allergy and Infectious Diseases (NIAID). And the Centers for Disease Control and Prevention lists N. gonorrhoeae among its “urgent” antibiotic resistance threats.

“I think we have a new superbug,” Dr. Deal said at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology. “In my opinion, it’s just a matter of time in this country.”

But three agents in late-stage clinical trials for uncomplicated urogenital gonorrhea offer promise in fighting the gram-negative bacteria, according to Dr. Deal. The first is solithromycin, manufactured by Cempra. The company has a phase III study underway to compare a single dose of oral solithromycin with intramuscular ceftriaxone plus oral azithromycin for urogenital gonorrhea.

The other two drugs are first-in-class antibacterial agents. In partnership with the NIAID, the company Entasis recently completed a phase II study of zoliflodacin, an oral agent in a novel class of topoisomerase inhibitors. A phase III trial is expected to begin in 2017, also in partnership with the NIAID, according to an Entasis document. The third agent is gepotidacin, a novel triazaacenaphthylene antibacterial agent currently being investigated by GlaxoSmithKline in a phase II study.

Centers for Disease Control and Prevention

Because N. gonorrhoeae poses such an urgent threat, waiting to develop a vaccine is less feasible than working with companies to develop additional antibacterial agents, Dr. Deal said. But taking a compound out of the basic research lab and having enough data to get into the investigational new drug phase is a significant investment, she said, so pharmaceutical manufacturers look for as many indications for a drug as possible.

For instance, solithromycin was initially investigated for community-acquired pneumonia. Gepotidacin initially was developed in partnership with the NIAID and the Biomedical Advanced Research and Development Authority in case of an anthrax attack, Dr. Deal said. “The Entasis product is the only one specifically developed for Neisseria gonorrhoeae,” she said.

One reason that two of the drugs in the pipeline include N. gonorrhoeae as an indication is that the Food and Drug Administration has issued guidance on developing drugs in the area of uncomplicated gonorrhea. That guidance is lacking for nasopharyngeal and rectal gonorrhea, leaving a “vacuum” in the pipeline, Dr. Deal said. “Many of us have come to the conclusion that developing vaccines is the only real long-term solution.”

[email protected]

On Twitter @whitneymcknight

ANNAPOLIS, MD. – Three novel treatments for gonorrhea, currently in late stages of development, could give clinicians an edge in the fight against antibacterial resistance, according to a federal health official.

The pathogen Neisseria gonorrhoeae is already showing signs of besting first-line therapy ceftriaxone in Japan and parts of Europe, said Carolyn Deal, PhD, chief of the sexually transmitted diseases branch at the National Institute of Allergy and Infectious Diseases (NIAID). And the Centers for Disease Control and Prevention lists N. gonorrhoeae among its “urgent” antibiotic resistance threats.

“I think we have a new superbug,” Dr. Deal said at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology. “In my opinion, it’s just a matter of time in this country.”

But three agents in late-stage clinical trials for uncomplicated urogenital gonorrhea offer promise in fighting the gram-negative bacteria, according to Dr. Deal. The first is solithromycin, manufactured by Cempra. The company has a phase III study underway to compare a single dose of oral solithromycin with intramuscular ceftriaxone plus oral azithromycin for urogenital gonorrhea.

The other two drugs are first-in-class antibacterial agents. In partnership with the NIAID, the company Entasis recently completed a phase II study of zoliflodacin, an oral agent in a novel class of topoisomerase inhibitors. A phase III trial is expected to begin in 2017, also in partnership with the NIAID, according to an Entasis document. The third agent is gepotidacin, a novel triazaacenaphthylene antibacterial agent currently being investigated by GlaxoSmithKline in a phase II study.

Centers for Disease Control and Prevention

Because N. gonorrhoeae poses such an urgent threat, waiting to develop a vaccine is less feasible than working with companies to develop additional antibacterial agents, Dr. Deal said. But taking a compound out of the basic research lab and having enough data to get into the investigational new drug phase is a significant investment, she said, so pharmaceutical manufacturers look for as many indications for a drug as possible.

For instance, solithromycin was initially investigated for community-acquired pneumonia. Gepotidacin initially was developed in partnership with the NIAID and the Biomedical Advanced Research and Development Authority in case of an anthrax attack, Dr. Deal said. “The Entasis product is the only one specifically developed for Neisseria gonorrhoeae,” she said.

One reason that two of the drugs in the pipeline include N. gonorrhoeae as an indication is that the Food and Drug Administration has issued guidance on developing drugs in the area of uncomplicated gonorrhea. That guidance is lacking for nasopharyngeal and rectal gonorrhea, leaving a “vacuum” in the pipeline, Dr. Deal said. “Many of us have come to the conclusion that developing vaccines is the only real long-term solution.”

[email protected]

On Twitter @whitneymcknight