Tapered antibiotics with kefir may be effective in recurrent C. difficile infection.
By Richard R. Watkins, MD, MS, FACP
Division of Infectious Diseases, Akron General Medical Center, Akron, OH; Associate Professor of Internal Medicine, Northeast Ohio Medcal University,m Rootstown, OH.
SYNOPSIS: A prospective case series that included patients with recurrent Clostridium difficile infection found that treatment with tapered antibiotic therapy and the probiotic drink kefir resulted in a clinical cure of 84% (21 out of 25 patients).
SOURCE: Bakken JS. Staggered and tapered antibiotic withdrawal with administration of kefir for recurrent Clostridium difficile infection. Clin Infect Dis 2014; advance access published 6/27/14; DOI:10.1093/cid/ciu429
Management of recurrent Clostridium difficile infection (CDI) is challenging. Fecal transplantation is becoming increasingly accepted for recurrent CDI after a recent report showed significantly improved outcomes compared with standard care. In this study, 81% of participants had resolution of C. difficile-associated diarrhea after the first stool infusion.1 However, many patients remain reluctant to undergo the procedure and it is not widely available. Thus, effective alternative therapies for recurrent CDI are needed. Kefir is a fermented dairy product with a diverse collection of probiotics that is commonly available in food stores. Bakken sought to determine if the addition of kefir to a tapered course of antibiotics would be effective in treating patients with recurrent CDI.
The study was a prospective case series from a single institution in Minnesota conducted between 2005 and 2013. The author treated 25 patients with a mean number of CDI relapses of 4 (range, 1-9). Between 2005 and 2006, an oral metronidazole taper was used along with a 5 oz glass of kefir with each meal or ad libitum as tolerated, and then from 2006 to 2013 an oral vancomycin taper along with kefir was prescribed. Also, the patients were instructed to continue to drink kefir for at least two months after finishing the antibiotics. The most common infections that preceded recurrent CDI were respiratory tract infection, diverticulitis and urinary tract infection. Ceftriaxone was the most common inciting antibiotic, followed by fluoroquinolones, azithromycin and clindamycin. Close to one-third of the patients were taking an H2 blocker and 4 patients were on immunosuppressive therapy.
All 25 patients had normal bowel function (i.e. no diarrhea) at the end of the antibiotic tapering therapy. However, 4 patients relapsed with CDI which was confirmed by a positive C. difficile assay between 24 and 45 days after completing the taper. These patients were then given a 2-week course of oral vancomycin 125 mg qid followed by a 2-week course of rifaximin 200 mg bid. Upon completing the vancomycin and rifaximin course, all 4 patients remained symptom-free after 12 months of follow-up. There was no association found between CDI relapse and H2-blocker usage, immunosuppressive therapy, comorbid illnesses, or predisposing infectious illnesses.
COMMENTARY
Data on the benefit of probiotics for CDI have been mixed. A Cochrane review that included 23 randomized controlled trials found moderate quality evidence that probiotics are both safe and effective for preventing Clostridium difficile-associated diarrhea.2 There are many kinds of probiotics sold over the counter and prescribed by physicians in health care settings. The choice of kefir in this study was interesting because, unlike conventional yogurt, it contains 7 to 10 billion colony forming units of 10 different bacterial strains (www.kefir.com). The investigator hypothesized that tapered antibiotic therapy would allow C. difficile spores to germinate during the drug-free periods and the kefir would replete and diversify the colon microbiome. Over time the pool of spores would be reduced and eventually subdued by the restored colonic flora. The primary treatment success rate of 84% seems to support the biologic plausibility that restoring the colon microbiome is the key to resolving recurrent CDI.
The study had some limitations. First, it had a small number of subjects and was conducted at a single institution. Thus, the results may not be generalizable to other settings or patient populations. Second, no control group was included, although the author stated that each patient served as his or her own control because they had all received oral antibiotics but not kefir for previous episodes of CDI. Finally, patient compliance with kefir was not directly reported.
For many patients, recurrent CDI is a devastating illness that profoundly impacts their quality of life. While fecal transplantation has been shown to be more effective than conventional antibiotic therapy for recurrent CDI, many insurance companies have been unwilling to cover the cost.
Based on this small study, kefir appears to be an effective adjunct to antibiotic tapering therapy without any observed risk. Larger, prospective studies on treatment of recurrent CDI that include kefir would be beneficial.
References
- Van Nood E, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013; 368(5):407-415.
- Goldenberg JZ, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev 2013; 5:CD006095.
