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What to D.O.

Evidence Backs Giving Probiotics with Antibiotics

Pescatore, Richard DO

doi: 10.1097/01.EEM.0000554841.70883.64
    probiotics, antibiotics
    probiotics, antibiotics:
    probiotics, antibiotics

    So much of what we're told to do calls for sweeping practice changes or titanic additions to our routine approach. My own articles have advocated for tremendous shifts in typical techniques, and one need not look far to find another recommendation for massive and cutting-edge changes to what we learned in residency or over years at the bedside.

    Sometimes, though, minimal additions can have monumental results. Such is the case with providing probiotics from the emergency department, a minor augmentation to practice with compelling evidence that it should have become standard of care long ago.

    Antibiotics are among the most commonly-prescribed medications from emergency departments, constituting nearly 20 percent of all ED prescriptions in one annual survey. (Natl Health Stat Report 2010;6[26]:1; Frustratingly, those same antibiotic prescriptions are responsible for a truly staggering amount of complications and a subsequent 150,000 annual ED visits for allergic reactions and other adverse events. (Clin Infect Dis 2008;47[6]:735;

    With nearly 40 percent of patients using antibiotics experiencing antibiotic-associated diarrhea (Dig Dis 1998;16[5]:292) and a growing incidence of Clostridium difficile colitis, intervention in this area clearly represents an opportunity for practice improvement and evidence-based progress.

    Probiotics, nonpathogenic bacteria (or yeast) that are largely normal intestinal flora, have become an increasingly popularized focus in the medical and lay literature. With growing interest in the idiosyncrasies of the gut microbiome, clinicians and armchair pharmacists alike have heralded probiotic supplementation for everything from treating gastroenteritis to daily supplementation for weight loss, skin rejuvenation, and even increased cognitive function. (Gastroenterology 2013;144[7]:1394;

    Predictably, the majority of these claims have continued to fall flat. (New Engl J Med 2018;379[21]:2015.) The microbiome, it seems, is dynamic, complex, and context-dependent, and attempting to manipulate this otherwise appropriately functioning system has proven fruitless.

    Patient Selection

    Prescribing probiotics alongside antibiotics seemed to be traversing a similar path with the publication of the PLACIDE trial in 2013. This large trial of nearly 3000 hospitalized elderly patients receiving antibiotics found no difference in the rates of antibiotic-associated diarrhea or C. diff colitis, though overall rates were strikingly low. (Lancet 2013;382[9900]:1249; Nonetheless, this trial prompted early guidelines recommending against co-prescribing probiotics and antibiotics, understandably interpreting PLACIDE as the latest example of the enduring failure of probiotics to achieve microbiotic harmony.

    Fortunately, however, undaunted researchers recognized the situational failings of the PLACIDE investigation. The seriously ill elderly receiving broad-spectrum parenteral agents are a critical area of study but poorly represent the more common provision of antimicrobials from the ED—systemically well patients with a local infectious process who are exposed to a short course of antibiotics to treat their pneumonia, urinary tract infection, or cellulitis.

    Probiotics are extremely effective in decreasing antibiotic-associated diarrhea and C. diff colitis when the institutionalized elderly are excluded. (Nutr Clin Pract 2016;31[4]:502.) The authors of a well-organized meta-analysis restricted to children found a number needed to treat (NNT) of only 10 to prevent antibiotic-associated diarrhea. (Cochrane Database Syst Rev 2015 Dec 22;(12):CD004827.) Reinforcing the importance of proper patient selection, the benefit persists in adults when probiotic use alongside outpatient antibiotics is principally examined. This review of nearly 100 randomized trials found an NNT of 25 to prevent C. diff colitis and just 13 to prevent antibiotic-associated diarrhea. (JAMA 2012;307[18]:1959;

    Clearly, probiotics have found their rightful and efficacious place in preventing antibiotic-associated diarrhea and C. diff colitis despite the negative results of the PLACIDE trial and previous contextual failings.

    Unfortunately, no compelling and consistent information exists about which probiotic agent might be best or in what formulation. Some studies used prepared lactobacillus or Bifidobacterium; others attempted saccharomyces yeast preparations or simply steered patients toward the yogurt aisle. Most studies have used lactobacillus preparations, but one trial compared six different formulations and found no difference among them. (Curr Ther Res 2001;62[5]:418.)

    Curiously, co-prescription of probiotics alongside antibiotics has found poor purchase in the emergency department despite these overwhelming and consistent data of benefit and a literature base much more extensive than many of the grander and more resource-intensive interventions we are called upon to adopt. It's unclear whether this is due to a dearth of advertising (probiotics are no pharmaceutical company's cash cow) or disbelief that such seemingly mild medications could have any significant benefit.

    Nonetheless, the data are clear: The small addition of probiotics to prevent antibiotic-associated diarrhea is an evidence-based and effective intervention that should be part of routine practice.

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    Dr. Pescatoreis the director of emergency medicine research for the Crozer-Keystone Health System in Chester, PA. He is also the host with Ali Raja, MD, of the podcast EMN Live, which focuses on hot topics in emergency medicine: Follow him on Twitter@Rick_Pescatore, and read his past columns at

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