Rifampin Associated With Lower Risk for C difficile Diarrhea

Daniel M. Keller, PhD

October 03, 2012

October 3, 2012 (San Francisco, California) — In a retrospective cohort study of patients with osteoarticular infections on long-term antibiotic therapy, combination therapy with oral rifampin was associated with an 82% reduction in the risk for Clostridium difficile–associated diarrhea (CDAD), compared with patients not receiving rifampin.

The results of the study, conducted by Caroline Landelle, PhD, from the infection control program at the University of Geneva Hospitals in Switzerland, and colleagues, were reported in a poster session here at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy.

The team looked at the development of CDAD in patients with osteoarticular infections, most of which were caused by staphylococci, from 1996 to 2006. Of the 393 treatment episodes, 55% were for infections after arthroplasty.

Mean age in the study cohort was 69 years (range, 6 to 93 years), 41% of the patients were female, and 31% were immunosuppressed. The researchers excluded patients who had had a previous C difficile infection, had received metronidazole treatment, or had had septic arthritis with short courses of therapy. The study hospital was nonendemic for C difficile ribotype 027.

Of the 401 organisms isolated, 32% were methicillin-sensitive Staphylococcus aureus; the rest were evenly divided among methicillin-resistant S aureus (16%), coagulase-negative staphylococci (17%), Gram-negative bacilli (17%), and other organisms (18%).

Antibiotic treatment ranged from 4 to 12 weeks (median, 8 weeks). In 45% of the treatment episodes, patients received intravenous vancomycin for a median of 13 days (range, 1 to 92 days). In 42% of the episodes, patients received rifampin 600 mg orally daily, as part of a combination antibiotic regimen, for a median of 53 days (range, 20 to 294 days).

CDAD Development a Rare Occurrence

Fourteen patients (3.6%) developed symptomatic CDAD after a median of 14 days of therapy. Of those, 6 (43%) had received vancomycin and 2 (14%) had received rifampin.

The authors report an inverse relation between rifampin use and CDAD, with an adjusted hazard ratio (aHR) of 0.18 (95% confidence interval [CI], 0.04 to 0.89; P = .04). In contrast, vancomycin use was not significantly associated with a reduction in the risk for CDAD (aHR, 0.86; 95% CI, 0.27 to 2.74; P = .80). The duration of antibiotic use was slightly but significantly associated with an increased risk for the development of CDAD (aHR, 1.01; 95% CI, 1.00 to 1.02; P = .01).

The investigators conclude that C difficile colitis is rare in patients with osteoarticular infections on long-term antibiotic therapy, but that oral rifampin, as part of combination antibiotic therapy, might protect against CDAD.

They note that rifamycin antibiotics have long been used in Switzerland but, unlike in many other countries, rifaximin is not licensed there for the treatment of hepatic encephalopathy, diarrhea, travelers diarrhea, or prophylaxis in gastrointestinal surgery. They say that this might explain the low level of rifampin resistance in C difficile in their hospital.

The study is interesting because "it shows that sometimes you have beneficial collateral effects from certain antibiotic choices," poster session moderator Stephan Harbarth, MD, MS, told Medscape Medical News. Dr. Harbarth is associate professor of medicine, attending physician in infectious diseases, and associate hospital epidemiologist at the Geneva University Hospitals, but was not involved in the work. He cited a recently published study that showed a probable protective effect of doxycycline against the development of clostridium infection.

"If you have rifampin and it is active against clostridium, it can decrease the chances of the selection of clostridium in the gut flora. This is something that makes sense," he explained. "However, you're not going to add rifampin to other antibiotic treatments just for the clostridium-protective bystander effect.... The best way to prevent clostridium is not to prescribe any antibiotics, of course."

Dr. Landelle and Dr. Harbarth have disclosed no relevant financial relationships.

52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract K-929. Presented September 9, 2012.