Probiotics for Antibiotic-Associated Diarrhea

Antibiotic-associated diarrhea (AAD) is an unfortunate clinical morbidity associated with our attempts to treat another clinical problem (i.e., infection). The most serious AAD is associated with Clostridium difficile; historically high rates of this infection have resulted in increased calls for “antibiotic stewardship.”

Despite our appropriate apprehensions about C. difficile, we commonly need to prescribe antibiotics in clinical practice. So what do we do to prevent “run of the mill” AAD? Although AAD does not occur in the majority of patients (~ 20%), we have patients who express concern about its occurrence and request advice on how to prevent it. Perhaps many of us have told our patients to eat yogurt or purchase over-the-counter probiotics. The efficacy of this approach has been controversial both because of uncertainty about effectiveness and concerns about side effects.

Earlier this month, Dr. Susanne Hempel of RAND Health and colleagues published a systematic review exploring the evidence for probiotic use in the prevention and treatment of AAD (JAMA. 2012;307:1959-69).

Recall that probiotics are micro-organisms intended to provide health benefits when consumed. Investigators searched for randomized controlled trials (RCTs) for both prevention and treatment. Probiotic interventions were primarily Lactobacillus-based, either alone or combined with other genera such as Bifidobacterium. Most studies explicitly administered probiotics to prevent or treat AAD. Across 63 RCTs (11,811 participants), probiotic use was associated with a lower relative risk (RR) of developing diarrhea compared to a control group not using a probiotic (RR, 0.58; 95% CI: 0.50 to 0.68; P< .001).

The exclusively Lactobacillus-based interventions (17 RCTs) reduced AAD [RR = 0.64; 95% CI: 0.47 to 0.86; P = .004; number needed to treat (NNT) = 14] and the exclusively yeast-based interventions (15 RCTs, Saccharomyces) reduced AAD (RR = 0.48; 95% CI: 0.35 to 0.65; P < .001; NNT = 10).
Adjunctive probiotic use for the treatment of Helicobacter pylori also was associated with benefit (RR = 0.55; 95% CI: 0.35 to 0.86; P = .009; NNT = 17).

In 14 RCTs, probiotics reduced the risk for C. difficile diarrhea (RR = 0.29; 95% CI: 0.17 to 0.48; P < .001; NNT = 25). Nineteen RCTs reported that no adverse events were judged to be associated with the use of probiotics.
Findings from this study are useful for clinicians alleviating patient concerns about AAD. Findings also may provide us with an intervention that may reduce infection with C. difficile.

So why are more of us not recommending probiotics? Perhaps our lack of familiarity with the variety of different products and the unavailability of standardized prescribing information are the most significant barriers to wider use. Companies with “skin in the game” on probiotics need to make this information more readily accessible to clinicians in order to increase recommendations for use of what appears to be a very effective intervention.

Jon O. Ebbert, M.D., is a professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. The opinions expressed are solely those of the author. Reach him by e-mail at ebbert.jon@mayo.edu.

Antibiotic-associated diarrhea (AAD) is an unfortunate clinical morbidity associated with our attempts to treat another clinical problem (i.e., infection). The most serious AAD is associated with Clostridium difficile; historically high rates of this infection have resulted in increased calls for “antibiotic stewardship.”

Despite our appropriate apprehensions about C. difficile, we commonly need to prescribe antibiotics in clinical practice. So what do we do to prevent “run of the mill” AAD? Although AAD does not occur in the majority of patients (~ 20%), we have patients who express concern about its occurrence and request advice on how to prevent it. Perhaps many of us have told our patients to eat yogurt or purchase over-the-counter probiotics. The efficacy of this approach has been controversial both because of uncertainty about effectiveness and concerns about side effects.

Earlier this month, Dr. Susanne Hempel of RAND Health and colleagues published a systematic review exploring the evidence for probiotic use in the prevention and treatment of AAD (JAMA. 2012;307:1959-69).

Recall that probiotics are micro-organisms intended to provide health benefits when consumed. Investigators searched for randomized controlled trials (RCTs) for both prevention and treatment. Probiotic interventions were primarily Lactobacillus-based, either alone or combined with other genera such as Bifidobacterium. Most studies explicitly administered probiotics to prevent or treat AAD. Across 63 RCTs (11,811 participants), probiotic use was associated with a lower relative risk (RR) of developing diarrhea compared to a control group not using a probiotic (RR, 0.58; 95% CI: 0.50 to 0.68; P< .001).

The exclusively Lactobacillus-based interventions (17 RCTs) reduced AAD [RR = 0.64; 95% CI: 0.47 to 0.86; P = .004; number needed to treat (NNT) = 14] and the exclusively yeast-based interventions (15 RCTs, Saccharomyces) reduced AAD (RR = 0.48; 95% CI: 0.35 to 0.65; P < .001; NNT = 10).
Adjunctive probiotic use for the treatment of Helicobacter pylori also was associated with benefit (RR = 0.55; 95% CI: 0.35 to 0.86; P = .009; NNT = 17).

In 14 RCTs, probiotics reduced the risk for C. difficile diarrhea (RR = 0.29; 95% CI: 0.17 to 0.48; P < .001; NNT = 25). Nineteen RCTs reported that no adverse events were judged to be associated with the use of probiotics.
Findings from this study are useful for clinicians alleviating patient concerns about AAD. Findings also may provide us with an intervention that may reduce infection with C. difficile.

So why are more of us not recommending probiotics? Perhaps our lack of familiarity with the variety of different products and the unavailability of standardized prescribing information are the most significant barriers to wider use. Companies with “skin in the game” on probiotics need to make this information more readily accessible to clinicians in order to increase recommendations for use of what appears to be a very effective intervention.

Jon O. Ebbert, M.D., is a professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. The opinions expressed are solely those of the author. Reach him by e-mail at ebbert.jon@mayo.edu.

Antibiotic-associated diarrhea (AAD) is an unfortunate clinical morbidity associated with our attempts to treat another clinical problem (i.e., infection). The most serious AAD is associated with Clostridium difficile; historically high rates of this infection have resulted in increased calls for “antibiotic stewardship.”

Despite our appropriate apprehensions about C. difficile, we commonly need to prescribe antibiotics in clinical practice. So what do we do to prevent “run of the mill” AAD? Although AAD does not occur in the majority of patients (~ 20%), we have patients who express concern about its occurrence and request advice on how to prevent it. Perhaps many of us have told our patients to eat yogurt or purchase over-the-counter probiotics. The efficacy of this approach has been controversial both because of uncertainty about effectiveness and concerns about side effects.

Earlier this month, Dr. Susanne Hempel of RAND Health and colleagues published a systematic review exploring the evidence for probiotic use in the prevention and treatment of AAD (JAMA. 2012;307:1959-69).

Recall that probiotics are micro-organisms intended to provide health benefits when consumed. Investigators searched for randomized controlled trials (RCTs) for both prevention and treatment. Probiotic interventions were primarily Lactobacillus-based, either alone or combined with other genera such as Bifidobacterium. Most studies explicitly administered probiotics to prevent or treat AAD. Across 63 RCTs (11,811 participants), probiotic use was associated with a lower relative risk (RR) of developing diarrhea compared to a control group not using a probiotic (RR, 0.58; 95% CI: 0.50 to 0.68; P< .001).

The exclusively Lactobacillus-based interventions (17 RCTs) reduced AAD [RR = 0.64; 95% CI: 0.47 to 0.86; P = .004; number needed to treat (NNT) = 14] and the exclusively yeast-based interventions (15 RCTs, Saccharomyces) reduced AAD (RR = 0.48; 95% CI: 0.35 to 0.65; P < .001; NNT = 10).
Adjunctive probiotic use for the treatment of Helicobacter pylori also was associated with benefit (RR = 0.55; 95% CI: 0.35 to 0.86; P = .009; NNT = 17).

In 14 RCTs, probiotics reduced the risk for C. difficile diarrhea (RR = 0.29; 95% CI: 0.17 to 0.48; P < .001; NNT = 25). Nineteen RCTs reported that no adverse events were judged to be associated with the use of probiotics.
Findings from this study are useful for clinicians alleviating patient concerns about AAD. Findings also may provide us with an intervention that may reduce infection with C. difficile.

So why are more of us not recommending probiotics? Perhaps our lack of familiarity with the variety of different products and the unavailability of standardized prescribing information are the most significant barriers to wider use. Companies with “skin in the game” on probiotics need to make this information more readily accessible to clinicians in order to increase recommendations for use of what appears to be a very effective intervention.

Jon O. Ebbert, M.D., is a professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. The opinions expressed are solely those of the author. Reach him by e-mail at ebbert.jon@mayo.edu.