Probiotic Use for the Prevention of Antibiotic- Associated Clostridium difficile Infection

Probiotic Safety

The FDA has not approved probiotics for the prevention or treatment of any health problems. Most probiotics are FDA-regulated as dietary supplements and do not have to meet stringent drug-approval requirements. The FDA has given many strains of common probiotics the Generally Recognized as Safe designation for use in commercially available products and foods.^21-23 Probiotic use has not been associated with significant AEs in clinical trials and generally has been considered safe in immunocompetent and otherwise healthy persons.^15-19 However, clinical trials have been inadequate in reporting or investigating AEs; the alternative for evaluating the risks of probiotic therapy is case reports.^24,25 Theoretical risks associated with probiotics include sepsis, deleterious effects on normal gut digestion, excessive immune stimulation, and possible transfer of antimicrobial resistance genes among microorganisms.²⁶ Boyle and colleagues further described a handful of case reports of sepsis caused by probiotics in immunocompromised individuals; the other theoretical risks have not been reported outside animal studies.²⁶

CDI Risk Factors

Many factors can increase a patient’s CDI risk. Specific antibiotics (eg, ampicillin, amoxicillin, cephalosporins, clindamycin, fluoroquinolones) confer higher risk.^27,28 Other factors include inflammatory bowel disease, organ transplantation, chemotherapy, chronic kidney disease, and immunodeficiency. Advanced age increases CDI risk and can increase the severity of infection. The evidence regarding acid suppression and CDI risk is conflicting, though a recent meta-analysis found that use of proton pump inhibitors is associated with a 2-fold higher risk of developing CDI.²⁹ Patient-specific risk factors should be evaluated when the risk–benefit ratio for probiotic use is being considered.

Conclusion

CDIs are becoming increasingly burdensome to the health care system. More research is needed on the role of probiotics in CDI prevention in patients taking antibiotics. Given the limited risk for AEs when probiotics are used in immunocompetent patients and the relatively low cost of these supplements, the risks likely are outweighed by the postulated benefits, and probiotics may be recommended in select patient populations.

The PLACIDE trial found no benefit of probiotics in preventing CDI in a population similar to that of a typical US hospital or ambulatory setting, but its intervention allowed late initiation of relatively low doses of probiotics. Therefore, probiotics may be recommended for CDI prevention in patients taking antibiotics, especially patients at high risk for developing CDI. When clinicians recommend probiotic use in this setting, the probiotic should be initiated within 2 days after the start of antibiotics and should be continued for the duration of antibiotic therapy and for up to 7 days after that therapy is completed. Optimal probiotic dosing, likely dependent on the product used, remains unclear. PLACIDE trial results suggest that a dosage of at least 1 probiotic capsule 2 times daily may confer additional efficacy.