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Inactivated Bifidobacterium improves IBS symptoms
pointing the way to a therapeutic path that could avoid some risks of live probiotic use.
Of 443 patients taking part in a randomized, double-blind, placebo-controlled trial of a heat-inactivated nonviable Bifidobacterium probiotic, 221 received the probiotic while 222 received placebo capsules. The study’s primary endpoint was a composite of at least 30% improvement in abdominal pain and “adequate relief” of overall irritable bowel syndrome (IBS) symptoms in at least 4 of the 8 weeks of the study.
Within the B. bifidum group, 74 patients (34%) reached this endpoint, compared with 43 (19%) of those in the placebo group, for a risk ratio of 1.7 (P = .0007). Patients had no serious adverse events from the oral therapy, which they took in the form of two capsules daily for 8 weeks, and participants found both the inactivated Bifidobacterium treatment and placebo tolerable overall.
Bowel movements became more frequent in those who received B. bifidum capsules who had constipation-predominant IBS and less frequent in those with diarrhea-predominant IBS; the changes were statistically significant in both subgroups.
“Some probiotic strains can adhere well to epithelial cells and strengthen intestinal barrier function, providing an explanation for the efficacy of at least some probiotics in the treatment of IBS,” wrote Viola Andresen, MD, MSc, the study‘s lead author.
“Accordingly, enhancing the gut barrier is a useful treatment approach for patients with IBS,” added Dr. Andresen, of the department of internal medicine at the University of Hamburg (Germany) Teaching Hospital, and collaborators. The adherent properties of some strains of Bifidobacteria are mainly dependent on properties of the cell surface that are not changed by heat inactivation, which makes the bacteria nonviable – and removes the risk of infection.
Additional benefits of using nonviable bacteria for IBS therapy might include more stability and enhanced standardization, although previous studies have shown a reduction in efficacy when bacteria are made nonviable. Inactivated B. bifidum MIMBb75 was used in this study because it had previously been shown effective against IBS symptoms, noted Dr. Andresen and coauthors.
Adult patients were included if they met criteria for IBS according to Rome III and had abdominal pain rated at least 4 on an 11-point scale for at least 2 days of a 2-week run-in phase. Among the many criteria for exclusion from the study were history of inflammatory gastrointestinal disease, cancer, other serious stomach diseases, diabetes, many abdominal surgeries, and recent antipsychotic or steroid use.
During the study, participants recorded their abdominal pain over the last 24 hours daily; weekly averages were tallied for each patient. Patients were also asked to rate their relief of IBS symptoms, including abdominal pain, bowel habits, and other symptoms over the past week at weekly time points on a 7-point Likert scale, where scores of 3 or less indicated some measure of relief; IBS symptoms were considered to be adequately relieved with a score of 3 or less.
Secondary outcome measures for the study included changes in the Subjects’ Global Assessment of symptoms, and changes in individual symptoms. Number of bowel movements, stool form, sensation of incomplete evacuation, and medication use were also recorded daily.
Participants were aged a mean of 41 years, and about 70% were female. The mean body mass index was just under 25 kg/m2. About half of each study arm had diarrhea-predominant IBS. About a quarter had constipation-predominant IBS, and most of the rest were not subtyped.
Looking at the primary endpoint, the number needed to treat for benefit was 7.1 in favor of the inactivated bacterium, using an intention-to-treat analysis. Results were similar when a per-protocol analysis was applied. The investigators saw response to treatment climb through the duration of the study for both the probiotic and the placebo arms, with the gap in improvement between the groups widening over the 8-week study period.
“It might be assumed that the use of nonviable bacteria for the treatment of IBS could be a safe alternative, even in patients who are potentially susceptible to infection,” concluded Dr. Andresen and colleagues. A further advantage, noted the researchers, is greater product stability in fluctuating temperatures compared with viable bacteria, ensuring better standardization even in regions with warm or changing climates.
Perspective was offered in an accompanying commentary whose lead author was Nicholas Talley, MD, PhD, a gastroenterologist, adjunct professor, and pro vice-chancellor for global research at the University of Newcastle (Australia).
“By heat inactivating the bacteria the researchers did not administer a probiotic but a bacterial therapy,” wrote Dr. Talley and coauthors. In any event, they added, the exact mechanism by which probiotics benefit individuals with IBS is unknown.
“The concept that a probiotic might be efficacious in IBS even if nonviable organisms are administered is an important observation,” they wrote. Fewer benefits have been seen with oral probiotic therapy than with fecal microbial transfer, and oral therapy does not produce durable results unless administered on a chronic basis, Dr. Talley and coauthors added.
“The absence of fundamental knowledge in terms of how bacterial therapy alters mechanisms in IBS continues to hamper improvements in treatment, limiting any success to short-term symptom control rather than the true goal, reversal of disease,” they concluded.
The study was funded by Synformulas. Dr. Andresen reported financial relationships with several pharmaceutical companies. Dr. Talley reported financial relationships with several pharmaceutical and nutritional companies.
SOURCE: Andresen V et al. Lancet Gastroenterol Hepatol. 2020 Apr 8. doi: 10.1016/S2468-1253(20)30079-0
pointing the way to a therapeutic path that could avoid some risks of live probiotic use.
Of 443 patients taking part in a randomized, double-blind, placebo-controlled trial of a heat-inactivated nonviable Bifidobacterium probiotic, 221 received the probiotic while 222 received placebo capsules. The study’s primary endpoint was a composite of at least 30% improvement in abdominal pain and “adequate relief” of overall irritable bowel syndrome (IBS) symptoms in at least 4 of the 8 weeks of the study.
Within the B. bifidum group, 74 patients (34%) reached this endpoint, compared with 43 (19%) of those in the placebo group, for a risk ratio of 1.7 (P = .0007). Patients had no serious adverse events from the oral therapy, which they took in the form of two capsules daily for 8 weeks, and participants found both the inactivated Bifidobacterium treatment and placebo tolerable overall.
Bowel movements became more frequent in those who received B. bifidum capsules who had constipation-predominant IBS and less frequent in those with diarrhea-predominant IBS; the changes were statistically significant in both subgroups.
“Some probiotic strains can adhere well to epithelial cells and strengthen intestinal barrier function, providing an explanation for the efficacy of at least some probiotics in the treatment of IBS,” wrote Viola Andresen, MD, MSc, the study‘s lead author.
“Accordingly, enhancing the gut barrier is a useful treatment approach for patients with IBS,” added Dr. Andresen, of the department of internal medicine at the University of Hamburg (Germany) Teaching Hospital, and collaborators. The adherent properties of some strains of Bifidobacteria are mainly dependent on properties of the cell surface that are not changed by heat inactivation, which makes the bacteria nonviable – and removes the risk of infection.
Additional benefits of using nonviable bacteria for IBS therapy might include more stability and enhanced standardization, although previous studies have shown a reduction in efficacy when bacteria are made nonviable. Inactivated B. bifidum MIMBb75 was used in this study because it had previously been shown effective against IBS symptoms, noted Dr. Andresen and coauthors.
Adult patients were included if they met criteria for IBS according to Rome III and had abdominal pain rated at least 4 on an 11-point scale for at least 2 days of a 2-week run-in phase. Among the many criteria for exclusion from the study were history of inflammatory gastrointestinal disease, cancer, other serious stomach diseases, diabetes, many abdominal surgeries, and recent antipsychotic or steroid use.
During the study, participants recorded their abdominal pain over the last 24 hours daily; weekly averages were tallied for each patient. Patients were also asked to rate their relief of IBS symptoms, including abdominal pain, bowel habits, and other symptoms over the past week at weekly time points on a 7-point Likert scale, where scores of 3 or less indicated some measure of relief; IBS symptoms were considered to be adequately relieved with a score of 3 or less.
Secondary outcome measures for the study included changes in the Subjects’ Global Assessment of symptoms, and changes in individual symptoms. Number of bowel movements, stool form, sensation of incomplete evacuation, and medication use were also recorded daily.
Participants were aged a mean of 41 years, and about 70% were female. The mean body mass index was just under 25 kg/m2. About half of each study arm had diarrhea-predominant IBS. About a quarter had constipation-predominant IBS, and most of the rest were not subtyped.
Looking at the primary endpoint, the number needed to treat for benefit was 7.1 in favor of the inactivated bacterium, using an intention-to-treat analysis. Results were similar when a per-protocol analysis was applied. The investigators saw response to treatment climb through the duration of the study for both the probiotic and the placebo arms, with the gap in improvement between the groups widening over the 8-week study period.
“It might be assumed that the use of nonviable bacteria for the treatment of IBS could be a safe alternative, even in patients who are potentially susceptible to infection,” concluded Dr. Andresen and colleagues. A further advantage, noted the researchers, is greater product stability in fluctuating temperatures compared with viable bacteria, ensuring better standardization even in regions with warm or changing climates.
Perspective was offered in an accompanying commentary whose lead author was Nicholas Talley, MD, PhD, a gastroenterologist, adjunct professor, and pro vice-chancellor for global research at the University of Newcastle (Australia).
“By heat inactivating the bacteria the researchers did not administer a probiotic but a bacterial therapy,” wrote Dr. Talley and coauthors. In any event, they added, the exact mechanism by which probiotics benefit individuals with IBS is unknown.
“The concept that a probiotic might be efficacious in IBS even if nonviable organisms are administered is an important observation,” they wrote. Fewer benefits have been seen with oral probiotic therapy than with fecal microbial transfer, and oral therapy does not produce durable results unless administered on a chronic basis, Dr. Talley and coauthors added.
“The absence of fundamental knowledge in terms of how bacterial therapy alters mechanisms in IBS continues to hamper improvements in treatment, limiting any success to short-term symptom control rather than the true goal, reversal of disease,” they concluded.
The study was funded by Synformulas. Dr. Andresen reported financial relationships with several pharmaceutical companies. Dr. Talley reported financial relationships with several pharmaceutical and nutritional companies.
SOURCE: Andresen V et al. Lancet Gastroenterol Hepatol. 2020 Apr 8. doi: 10.1016/S2468-1253(20)30079-0
pointing the way to a therapeutic path that could avoid some risks of live probiotic use.
Of 443 patients taking part in a randomized, double-blind, placebo-controlled trial of a heat-inactivated nonviable Bifidobacterium probiotic, 221 received the probiotic while 222 received placebo capsules. The study’s primary endpoint was a composite of at least 30% improvement in abdominal pain and “adequate relief” of overall irritable bowel syndrome (IBS) symptoms in at least 4 of the 8 weeks of the study.
Within the B. bifidum group, 74 patients (34%) reached this endpoint, compared with 43 (19%) of those in the placebo group, for a risk ratio of 1.7 (P = .0007). Patients had no serious adverse events from the oral therapy, which they took in the form of two capsules daily for 8 weeks, and participants found both the inactivated Bifidobacterium treatment and placebo tolerable overall.
Bowel movements became more frequent in those who received B. bifidum capsules who had constipation-predominant IBS and less frequent in those with diarrhea-predominant IBS; the changes were statistically significant in both subgroups.
“Some probiotic strains can adhere well to epithelial cells and strengthen intestinal barrier function, providing an explanation for the efficacy of at least some probiotics in the treatment of IBS,” wrote Viola Andresen, MD, MSc, the study‘s lead author.
“Accordingly, enhancing the gut barrier is a useful treatment approach for patients with IBS,” added Dr. Andresen, of the department of internal medicine at the University of Hamburg (Germany) Teaching Hospital, and collaborators. The adherent properties of some strains of Bifidobacteria are mainly dependent on properties of the cell surface that are not changed by heat inactivation, which makes the bacteria nonviable – and removes the risk of infection.
Additional benefits of using nonviable bacteria for IBS therapy might include more stability and enhanced standardization, although previous studies have shown a reduction in efficacy when bacteria are made nonviable. Inactivated B. bifidum MIMBb75 was used in this study because it had previously been shown effective against IBS symptoms, noted Dr. Andresen and coauthors.
Adult patients were included if they met criteria for IBS according to Rome III and had abdominal pain rated at least 4 on an 11-point scale for at least 2 days of a 2-week run-in phase. Among the many criteria for exclusion from the study were history of inflammatory gastrointestinal disease, cancer, other serious stomach diseases, diabetes, many abdominal surgeries, and recent antipsychotic or steroid use.
During the study, participants recorded their abdominal pain over the last 24 hours daily; weekly averages were tallied for each patient. Patients were also asked to rate their relief of IBS symptoms, including abdominal pain, bowel habits, and other symptoms over the past week at weekly time points on a 7-point Likert scale, where scores of 3 or less indicated some measure of relief; IBS symptoms were considered to be adequately relieved with a score of 3 or less.
Secondary outcome measures for the study included changes in the Subjects’ Global Assessment of symptoms, and changes in individual symptoms. Number of bowel movements, stool form, sensation of incomplete evacuation, and medication use were also recorded daily.
Participants were aged a mean of 41 years, and about 70% were female. The mean body mass index was just under 25 kg/m2. About half of each study arm had diarrhea-predominant IBS. About a quarter had constipation-predominant IBS, and most of the rest were not subtyped.
Looking at the primary endpoint, the number needed to treat for benefit was 7.1 in favor of the inactivated bacterium, using an intention-to-treat analysis. Results were similar when a per-protocol analysis was applied. The investigators saw response to treatment climb through the duration of the study for both the probiotic and the placebo arms, with the gap in improvement between the groups widening over the 8-week study period.
“It might be assumed that the use of nonviable bacteria for the treatment of IBS could be a safe alternative, even in patients who are potentially susceptible to infection,” concluded Dr. Andresen and colleagues. A further advantage, noted the researchers, is greater product stability in fluctuating temperatures compared with viable bacteria, ensuring better standardization even in regions with warm or changing climates.
Perspective was offered in an accompanying commentary whose lead author was Nicholas Talley, MD, PhD, a gastroenterologist, adjunct professor, and pro vice-chancellor for global research at the University of Newcastle (Australia).
“By heat inactivating the bacteria the researchers did not administer a probiotic but a bacterial therapy,” wrote Dr. Talley and coauthors. In any event, they added, the exact mechanism by which probiotics benefit individuals with IBS is unknown.
“The concept that a probiotic might be efficacious in IBS even if nonviable organisms are administered is an important observation,” they wrote. Fewer benefits have been seen with oral probiotic therapy than with fecal microbial transfer, and oral therapy does not produce durable results unless administered on a chronic basis, Dr. Talley and coauthors added.
“The absence of fundamental knowledge in terms of how bacterial therapy alters mechanisms in IBS continues to hamper improvements in treatment, limiting any success to short-term symptom control rather than the true goal, reversal of disease,” they concluded.
The study was funded by Synformulas. Dr. Andresen reported financial relationships with several pharmaceutical companies. Dr. Talley reported financial relationships with several pharmaceutical and nutritional companies.
SOURCE: Andresen V et al. Lancet Gastroenterol Hepatol. 2020 Apr 8. doi: 10.1016/S2468-1253(20)30079-0
FROM THE LANCET GASTROENTEROLOGY AND HEPATOLOGY
Arsenic levels in infant rice cereal are down
according to test results released by the Food and Drug Administration.
In April 2016, the FDA issued draft guidance calling for manufacturers of the product to reduce the level of arsenic in their cereals by establishing an action level of arsenic of 100 mcg/kg or 100 parts per billion.
Seventy-six percent of samples of infant rice cereal tested in 2018 had levels of arsenic at or below 100 parts per billion versus 47% of samples tested in 2014, according to a statement from the FDA. In 2011-2013, an even lower percentage of samples tested contained amounts of inorganic arsenic at or below the FDA’s current action level for this element, whose consumption has been associated with cancer, skin lesions, cardiovascular diseases, and diabetes.
The 2018 data is based on the testing of 149 samples of infant white and brown rice cereal samples.
“Results from our tests show that manufacturers have made significant progress in ensuring lower levels of inorganic arsenic in infant rice cereal,” Susan Mayne, PhD, director of the Center for Food Safety and Applied Nutrition, said in the FDA statement.
“Both white rice and brown rice cereals showed improvement in meeting the FDA’s 100 ppb proposed action level, but the improvement was greatest for white rice cereals, which tend to have lower levels of inorganic arsenic overall,” according to the statement.
according to test results released by the Food and Drug Administration.
In April 2016, the FDA issued draft guidance calling for manufacturers of the product to reduce the level of arsenic in their cereals by establishing an action level of arsenic of 100 mcg/kg or 100 parts per billion.
Seventy-six percent of samples of infant rice cereal tested in 2018 had levels of arsenic at or below 100 parts per billion versus 47% of samples tested in 2014, according to a statement from the FDA. In 2011-2013, an even lower percentage of samples tested contained amounts of inorganic arsenic at or below the FDA’s current action level for this element, whose consumption has been associated with cancer, skin lesions, cardiovascular diseases, and diabetes.
The 2018 data is based on the testing of 149 samples of infant white and brown rice cereal samples.
“Results from our tests show that manufacturers have made significant progress in ensuring lower levels of inorganic arsenic in infant rice cereal,” Susan Mayne, PhD, director of the Center for Food Safety and Applied Nutrition, said in the FDA statement.
“Both white rice and brown rice cereals showed improvement in meeting the FDA’s 100 ppb proposed action level, but the improvement was greatest for white rice cereals, which tend to have lower levels of inorganic arsenic overall,” according to the statement.
according to test results released by the Food and Drug Administration.
In April 2016, the FDA issued draft guidance calling for manufacturers of the product to reduce the level of arsenic in their cereals by establishing an action level of arsenic of 100 mcg/kg or 100 parts per billion.
Seventy-six percent of samples of infant rice cereal tested in 2018 had levels of arsenic at or below 100 parts per billion versus 47% of samples tested in 2014, according to a statement from the FDA. In 2011-2013, an even lower percentage of samples tested contained amounts of inorganic arsenic at or below the FDA’s current action level for this element, whose consumption has been associated with cancer, skin lesions, cardiovascular diseases, and diabetes.
The 2018 data is based on the testing of 149 samples of infant white and brown rice cereal samples.
“Results from our tests show that manufacturers have made significant progress in ensuring lower levels of inorganic arsenic in infant rice cereal,” Susan Mayne, PhD, director of the Center for Food Safety and Applied Nutrition, said in the FDA statement.
“Both white rice and brown rice cereals showed improvement in meeting the FDA’s 100 ppb proposed action level, but the improvement was greatest for white rice cereals, which tend to have lower levels of inorganic arsenic overall,” according to the statement.
Prevention and Treatment of Traveler’s Diarrhea
Importance
The prevention and treatment of traveler’s diarrhea (TD) is a common reason that patients consult their physician prior to foreign travel. TD can result in lost time and opportunity, as well as overseas medical encounters and hospitalization. to providers regarding the use of antibiotic and nonantibiotic therapies for the prevention and treatment of TD.
Prophylaxis
The panel recommends that antimicrobial prophylaxis should not be used routinely in travelers, but it should be considered for travelers who are at high risk of health-related complications of TD (both strong recommendations, low/very low level of evidence [LOE]). High-risk individuals include those with a history of clinically significant long-term morbidity following an enteric infection or serious chronic illnesses that predisposes them for TD-related complications. Bismuth subsalicylate (BSS) may be considered for any traveler to prevent TD (3, strong recommendation, high LOE). Studies show that a lower dose of 1.05 g/day is preventive, although it is unclear whether it is as effective as higher doses of 2.1 g/day or 4.2 g/day. When prophylaxis is indicated, travelers should be prescribed rifaximin (strong recommendation, moderate LOE) based on susceptibility of most enteric pathogens and the drug’s extremely favorable safety profile. Fluoroquinolones (FQ) are no longer recommended for prophylaxis (strong recommendation, low/very low LOE) because of neurologic and musculoskeletal side effects that may outweigh benefits, as well as emerging resistance of enteric pathogens (70%-80% in Campylobacter spp. from Nepal and Thailand and 65% in Enterotoxigenic Escherichia coli [ETEC] and Enteroaggregative E. coli [EAEC] in India).
Treatment
The following treatment recommendations are based on the classification of TD using functional effects of severity; therefore, the panel made new definitions for TD severity. This is a change from previous definitions that utilized a traditional frequency-based algorithm in order to tailor therapy for the individual. Individuals can be prescribed antibiotics and antimotility agents to take with them during travel, along with advice regarding how to judge when to use each agent.
Mild: diarrhea that is tolerable, is not distressing, and does not interfere with planned activities.
Encourage supportive measures such as rehydration and nonantibiotic, antimotility drugs, such as loperamide or BSS (both strong recommendations, moderate LOE).
Moderate: diarrhea that is distressing or interferes with planned activities.
Antibiotics may be used (weak recommendation, moderate LOE) as early and effective treatment may mitigate the well-described chronic health consequences including irritable bowel syndrome. Three options exist. FQs may be used outside of Southeast and South Asia (strong recommendation, moderate LOE), but their potential for adverse effects and musculoskeletal consequences must be considered. Azithromycin may be used (strong recommendation, high LOE) because studies show no significant differences in efficacy between it and FQs, limited resistance to common TD pathogens (although concerns exist in Nepal), and good side effect profile. Another choice is rifaximin (weak recommendation, moderate LOE), although one should exercise caution for empirical therapy in regions in which being at high risk of invasive pathogens is anticipated.
Loperamide may be used as adjunctive therapy for moderate to severe TD (strong recommendation, high LOE) to add symptomatic relief with curative treatment or as monotherapy in moderate TD (strong recommendation, high LOE). This is specifically true in children aged 2-11 years, in whom loperamide is beneficial without causing severe side effects.
Severe: diarrhea that is incapacitating or completely prevents planned activities; all dysentery (passage of grossly bloody stools).
Antibiotics should be used (strong recommendation, high LOE). Azithromycin is the preferred choice and is first-line for dysentery or febrile diarrhea (strong recommendation, moderate LOE) because of the likelihood of FQ-resistant bacteria being the cause of dysentery. FQs and rifaximin are also choices that can be used to treat severe, nondysenteric TD (both weak recommendations, moderate LOE).
Furthermore, single-dose antibiotics may be used to treat moderate or severe TD (strong recommendation, high LOE) because studies have shown equivalent efficacy for treatment of watery noninvasive diarrhea among FQs (3 days, single dose), azithromycin (3 days, single dose), and rifaximin (3 days, three times daily).
Persistent: diarrhea lasting longer than 2 weeks.
Functional bowel disease (FBD) may occur after bouts of TD and may meet Rome III or IV criteria for irritable bowel syndrome. Thus, in a traveler without pretravel GI disease, in whom the evaluation for microbial etiologies and underlying GI disease is negative, postinfectious FBD must be considered.
Follow-up and diagnostic testing
The panel recommends microbiological testing in returning travelers with severe or persistent symptoms, bloody/mucousy diarrhea, or in those who fail empiric therapy (strong recommendation, low/very low LOE). Molecular testing, aimed at a broad range of clinically relevant pathogens, is preferred when rapid results are clinically important or nonmolecular tests have failed to establish a diagnosis. Furthermore, molecular testing may, in some cases, detect colonization rather than infection.
The bottom line
The expert panel made 20 graded recommendations to help guide the provider with nonantibiotic and antibiotic prophylaxis and treatment of TD. The main take-home points include:
- Prophylaxis should be considered only in high-risk groups; rifaximin is the first choice, and BSS is a second option.
- All travelers should be provided with loperamide and an antibiotic for self-treatment if needed.
- Mild diarrhea should be treated with increased fluid intake and loperamide or BSS.
- Moderate to severe diarrhea should be treated with single-dose antimicrobial therapy of FQ or azithromycin or with rifaximin dosing three times a day.
- Instead of antibiotics, loperamide may be considered as monotherapy for moderate diarrhea; loperamide can be used with antibiotics for both moderate and severe TD.
Dr. Shrestha is a second-year resident in the Family Medicine Residency Program at Abington (Pa.) - Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington - Jefferson Health.
Reference:
Importance
The prevention and treatment of traveler’s diarrhea (TD) is a common reason that patients consult their physician prior to foreign travel. TD can result in lost time and opportunity, as well as overseas medical encounters and hospitalization. to providers regarding the use of antibiotic and nonantibiotic therapies for the prevention and treatment of TD.
Prophylaxis
The panel recommends that antimicrobial prophylaxis should not be used routinely in travelers, but it should be considered for travelers who are at high risk of health-related complications of TD (both strong recommendations, low/very low level of evidence [LOE]). High-risk individuals include those with a history of clinically significant long-term morbidity following an enteric infection or serious chronic illnesses that predisposes them for TD-related complications. Bismuth subsalicylate (BSS) may be considered for any traveler to prevent TD (3, strong recommendation, high LOE). Studies show that a lower dose of 1.05 g/day is preventive, although it is unclear whether it is as effective as higher doses of 2.1 g/day or 4.2 g/day. When prophylaxis is indicated, travelers should be prescribed rifaximin (strong recommendation, moderate LOE) based on susceptibility of most enteric pathogens and the drug’s extremely favorable safety profile. Fluoroquinolones (FQ) are no longer recommended for prophylaxis (strong recommendation, low/very low LOE) because of neurologic and musculoskeletal side effects that may outweigh benefits, as well as emerging resistance of enteric pathogens (70%-80% in Campylobacter spp. from Nepal and Thailand and 65% in Enterotoxigenic Escherichia coli [ETEC] and Enteroaggregative E. coli [EAEC] in India).
Treatment
The following treatment recommendations are based on the classification of TD using functional effects of severity; therefore, the panel made new definitions for TD severity. This is a change from previous definitions that utilized a traditional frequency-based algorithm in order to tailor therapy for the individual. Individuals can be prescribed antibiotics and antimotility agents to take with them during travel, along with advice regarding how to judge when to use each agent.
Mild: diarrhea that is tolerable, is not distressing, and does not interfere with planned activities.
Encourage supportive measures such as rehydration and nonantibiotic, antimotility drugs, such as loperamide or BSS (both strong recommendations, moderate LOE).
Moderate: diarrhea that is distressing or interferes with planned activities.
Antibiotics may be used (weak recommendation, moderate LOE) as early and effective treatment may mitigate the well-described chronic health consequences including irritable bowel syndrome. Three options exist. FQs may be used outside of Southeast and South Asia (strong recommendation, moderate LOE), but their potential for adverse effects and musculoskeletal consequences must be considered. Azithromycin may be used (strong recommendation, high LOE) because studies show no significant differences in efficacy between it and FQs, limited resistance to common TD pathogens (although concerns exist in Nepal), and good side effect profile. Another choice is rifaximin (weak recommendation, moderate LOE), although one should exercise caution for empirical therapy in regions in which being at high risk of invasive pathogens is anticipated.
Loperamide may be used as adjunctive therapy for moderate to severe TD (strong recommendation, high LOE) to add symptomatic relief with curative treatment or as monotherapy in moderate TD (strong recommendation, high LOE). This is specifically true in children aged 2-11 years, in whom loperamide is beneficial without causing severe side effects.
Severe: diarrhea that is incapacitating or completely prevents planned activities; all dysentery (passage of grossly bloody stools).
Antibiotics should be used (strong recommendation, high LOE). Azithromycin is the preferred choice and is first-line for dysentery or febrile diarrhea (strong recommendation, moderate LOE) because of the likelihood of FQ-resistant bacteria being the cause of dysentery. FQs and rifaximin are also choices that can be used to treat severe, nondysenteric TD (both weak recommendations, moderate LOE).
Furthermore, single-dose antibiotics may be used to treat moderate or severe TD (strong recommendation, high LOE) because studies have shown equivalent efficacy for treatment of watery noninvasive diarrhea among FQs (3 days, single dose), azithromycin (3 days, single dose), and rifaximin (3 days, three times daily).
Persistent: diarrhea lasting longer than 2 weeks.
Functional bowel disease (FBD) may occur after bouts of TD and may meet Rome III or IV criteria for irritable bowel syndrome. Thus, in a traveler without pretravel GI disease, in whom the evaluation for microbial etiologies and underlying GI disease is negative, postinfectious FBD must be considered.
Follow-up and diagnostic testing
The panel recommends microbiological testing in returning travelers with severe or persistent symptoms, bloody/mucousy diarrhea, or in those who fail empiric therapy (strong recommendation, low/very low LOE). Molecular testing, aimed at a broad range of clinically relevant pathogens, is preferred when rapid results are clinically important or nonmolecular tests have failed to establish a diagnosis. Furthermore, molecular testing may, in some cases, detect colonization rather than infection.
The bottom line
The expert panel made 20 graded recommendations to help guide the provider with nonantibiotic and antibiotic prophylaxis and treatment of TD. The main take-home points include:
- Prophylaxis should be considered only in high-risk groups; rifaximin is the first choice, and BSS is a second option.
- All travelers should be provided with loperamide and an antibiotic for self-treatment if needed.
- Mild diarrhea should be treated with increased fluid intake and loperamide or BSS.
- Moderate to severe diarrhea should be treated with single-dose antimicrobial therapy of FQ or azithromycin or with rifaximin dosing three times a day.
- Instead of antibiotics, loperamide may be considered as monotherapy for moderate diarrhea; loperamide can be used with antibiotics for both moderate and severe TD.
Dr. Shrestha is a second-year resident in the Family Medicine Residency Program at Abington (Pa.) - Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington - Jefferson Health.
Reference:
Importance
The prevention and treatment of traveler’s diarrhea (TD) is a common reason that patients consult their physician prior to foreign travel. TD can result in lost time and opportunity, as well as overseas medical encounters and hospitalization. to providers regarding the use of antibiotic and nonantibiotic therapies for the prevention and treatment of TD.
Prophylaxis
The panel recommends that antimicrobial prophylaxis should not be used routinely in travelers, but it should be considered for travelers who are at high risk of health-related complications of TD (both strong recommendations, low/very low level of evidence [LOE]). High-risk individuals include those with a history of clinically significant long-term morbidity following an enteric infection or serious chronic illnesses that predisposes them for TD-related complications. Bismuth subsalicylate (BSS) may be considered for any traveler to prevent TD (3, strong recommendation, high LOE). Studies show that a lower dose of 1.05 g/day is preventive, although it is unclear whether it is as effective as higher doses of 2.1 g/day or 4.2 g/day. When prophylaxis is indicated, travelers should be prescribed rifaximin (strong recommendation, moderate LOE) based on susceptibility of most enteric pathogens and the drug’s extremely favorable safety profile. Fluoroquinolones (FQ) are no longer recommended for prophylaxis (strong recommendation, low/very low LOE) because of neurologic and musculoskeletal side effects that may outweigh benefits, as well as emerging resistance of enteric pathogens (70%-80% in Campylobacter spp. from Nepal and Thailand and 65% in Enterotoxigenic Escherichia coli [ETEC] and Enteroaggregative E. coli [EAEC] in India).
Treatment
The following treatment recommendations are based on the classification of TD using functional effects of severity; therefore, the panel made new definitions for TD severity. This is a change from previous definitions that utilized a traditional frequency-based algorithm in order to tailor therapy for the individual. Individuals can be prescribed antibiotics and antimotility agents to take with them during travel, along with advice regarding how to judge when to use each agent.
Mild: diarrhea that is tolerable, is not distressing, and does not interfere with planned activities.
Encourage supportive measures such as rehydration and nonantibiotic, antimotility drugs, such as loperamide or BSS (both strong recommendations, moderate LOE).
Moderate: diarrhea that is distressing or interferes with planned activities.
Antibiotics may be used (weak recommendation, moderate LOE) as early and effective treatment may mitigate the well-described chronic health consequences including irritable bowel syndrome. Three options exist. FQs may be used outside of Southeast and South Asia (strong recommendation, moderate LOE), but their potential for adverse effects and musculoskeletal consequences must be considered. Azithromycin may be used (strong recommendation, high LOE) because studies show no significant differences in efficacy between it and FQs, limited resistance to common TD pathogens (although concerns exist in Nepal), and good side effect profile. Another choice is rifaximin (weak recommendation, moderate LOE), although one should exercise caution for empirical therapy in regions in which being at high risk of invasive pathogens is anticipated.
Loperamide may be used as adjunctive therapy for moderate to severe TD (strong recommendation, high LOE) to add symptomatic relief with curative treatment or as monotherapy in moderate TD (strong recommendation, high LOE). This is specifically true in children aged 2-11 years, in whom loperamide is beneficial without causing severe side effects.
Severe: diarrhea that is incapacitating or completely prevents planned activities; all dysentery (passage of grossly bloody stools).
Antibiotics should be used (strong recommendation, high LOE). Azithromycin is the preferred choice and is first-line for dysentery or febrile diarrhea (strong recommendation, moderate LOE) because of the likelihood of FQ-resistant bacteria being the cause of dysentery. FQs and rifaximin are also choices that can be used to treat severe, nondysenteric TD (both weak recommendations, moderate LOE).
Furthermore, single-dose antibiotics may be used to treat moderate or severe TD (strong recommendation, high LOE) because studies have shown equivalent efficacy for treatment of watery noninvasive diarrhea among FQs (3 days, single dose), azithromycin (3 days, single dose), and rifaximin (3 days, three times daily).
Persistent: diarrhea lasting longer than 2 weeks.
Functional bowel disease (FBD) may occur after bouts of TD and may meet Rome III or IV criteria for irritable bowel syndrome. Thus, in a traveler without pretravel GI disease, in whom the evaluation for microbial etiologies and underlying GI disease is negative, postinfectious FBD must be considered.
Follow-up and diagnostic testing
The panel recommends microbiological testing in returning travelers with severe or persistent symptoms, bloody/mucousy diarrhea, or in those who fail empiric therapy (strong recommendation, low/very low LOE). Molecular testing, aimed at a broad range of clinically relevant pathogens, is preferred when rapid results are clinically important or nonmolecular tests have failed to establish a diagnosis. Furthermore, molecular testing may, in some cases, detect colonization rather than infection.
The bottom line
The expert panel made 20 graded recommendations to help guide the provider with nonantibiotic and antibiotic prophylaxis and treatment of TD. The main take-home points include:
- Prophylaxis should be considered only in high-risk groups; rifaximin is the first choice, and BSS is a second option.
- All travelers should be provided with loperamide and an antibiotic for self-treatment if needed.
- Mild diarrhea should be treated with increased fluid intake and loperamide or BSS.
- Moderate to severe diarrhea should be treated with single-dose antimicrobial therapy of FQ or azithromycin or with rifaximin dosing three times a day.
- Instead of antibiotics, loperamide may be considered as monotherapy for moderate diarrhea; loperamide can be used with antibiotics for both moderate and severe TD.
Dr. Shrestha is a second-year resident in the Family Medicine Residency Program at Abington (Pa.) - Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington - Jefferson Health.