Rifampin Combinations May Protect Against C. difficile Colitis

SAN FRANCISCO – The addition of rifampin to long-term antibiotic regimens significantly lowers the risk for Clostridium difficile–associated colitis in patients being treated for osteoarticular infections.

The retrospective cohort study comprised 393 treatment episodes – 55% of them for infections subsequent to arthroplasty – among patients admitted to a Swiss orthopedic surgery unit from 1996 to 2012. The ribotype 027 was not endemic in the region.

The 42% of patients who were treated with combination therapy that included oral rifampin (600 mg/day) were significantly less like to develop C. difficile colitis despite being on the antibiotics for a median of 63 days (ranging from 20-294 days), Caroline Landelle, Pharm.D., Ph.D. and her associates reported at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Rifampin use was inversely associated with C. difficile colitis, with an adjusted hazard ratio of 0.18, Dr. Landelle reported in a poster presentation.

In general, longer duration of antibiotics treatment was associated with C. difficile colitis, with an adjusted hazard ratio of 1.01, said Dr. Landelle of the University of Geneva.

Factors not associated with colitis risk (either positively or negatively) included the use of antianaerobic antibiotics (in 38% of patients), treatment with intravenous vancomycin (in 45%, for a median of 13 days), age, or sex.

Fourteen patients (4%) developed symptomatic C. difficile colitis after a median of 14 days of antibiotic treatment (ranging from 8-193 days). Of these, six patients were on vancomycin (43%) and two patients were receiving rifampin (14%) prior to development of the colitis, Dr. Landelle reported at the meeting, sponsored by the American Society for Microbiology.

"C. difficile colitis was rare despite long-term antibiotic use among patients with osteoarticular infection. In contrast to intravenous vancomycin, combination antibiotic therapy with oral rifampin might protect against C. difficile–associated colitis," the investigators suggested.

The cohort had a median age of 69 years; 41% was female, and 31% of patients were immunosuppressed.

Of the 401 microorganisms isolated from the osteoarticular infections, 32% were methicillin-sensitive Staphylococcus aureus, 16% were methicillin-resistant S. aureus, 17% each were coagulase-negative Staphylococcus or gram-negative bacilli, and 18% were other organisms.

The investigators hypothesized that combination therapy with rifampin or derivative medications might protect against C. difficile colitis because very few cases have been reported of rifampin-associated pseudomembranous colitis, and patients undergoing treatment with long-term antibiotic combination therapy for osteoarticular infections rarely develop symptomatic C. difficile–associated disease.

Rifaximin and other antibiotics belonging to the macrocyclic family are being investigated as alternative therapies for C. difficile–associated disease, Dr. Landelle said. Some studies have shown high rates of C. difficile resistance to rifampin in Europe, but the rate of resistance at her institution was low. In Switzerland, rifamycin antibiotics have been used for decades, but rifaximin is not licensed for the treatment of hepatic encephalopathy, diarrhea, and traveler’s diarrhea or for prophylaxis in patients undergoing GI surgery, which may explain the low rate of resistance there.

The study excluded patients with prior episodes of C. difficile–associated disease, patients being treated with metronidazole, and patients with septic arthritis.

Dr. Landelle did not provide her financial disclosures.

SAN FRANCISCO – The addition of rifampin to long-term antibiotic regimens significantly lowers the risk for Clostridium difficile–associated colitis in patients being treated for osteoarticular infections.

The retrospective cohort study comprised 393 treatment episodes – 55% of them for infections subsequent to arthroplasty – among patients admitted to a Swiss orthopedic surgery unit from 1996 to 2012. The ribotype 027 was not endemic in the region.

The 42% of patients who were treated with combination therapy that included oral rifampin (600 mg/day) were significantly less like to develop C. difficile colitis despite being on the antibiotics for a median of 63 days (ranging from 20-294 days), Caroline Landelle, Pharm.D., Ph.D. and her associates reported at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Rifampin use was inversely associated with C. difficile colitis, with an adjusted hazard ratio of 0.18, Dr. Landelle reported in a poster presentation.

In general, longer duration of antibiotics treatment was associated with C. difficile colitis, with an adjusted hazard ratio of 1.01, said Dr. Landelle of the University of Geneva.

Factors not associated with colitis risk (either positively or negatively) included the use of antianaerobic antibiotics (in 38% of patients), treatment with intravenous vancomycin (in 45%, for a median of 13 days), age, or sex.

Fourteen patients (4%) developed symptomatic C. difficile colitis after a median of 14 days of antibiotic treatment (ranging from 8-193 days). Of these, six patients were on vancomycin (43%) and two patients were receiving rifampin (14%) prior to development of the colitis, Dr. Landelle reported at the meeting, sponsored by the American Society for Microbiology.

"C. difficile colitis was rare despite long-term antibiotic use among patients with osteoarticular infection. In contrast to intravenous vancomycin, combination antibiotic therapy with oral rifampin might protect against C. difficile–associated colitis," the investigators suggested.

The cohort had a median age of 69 years; 41% was female, and 31% of patients were immunosuppressed.

Of the 401 microorganisms isolated from the osteoarticular infections, 32% were methicillin-sensitive Staphylococcus aureus, 16% were methicillin-resistant S. aureus, 17% each were coagulase-negative Staphylococcus or gram-negative bacilli, and 18% were other organisms.

The investigators hypothesized that combination therapy with rifampin or derivative medications might protect against C. difficile colitis because very few cases have been reported of rifampin-associated pseudomembranous colitis, and patients undergoing treatment with long-term antibiotic combination therapy for osteoarticular infections rarely develop symptomatic C. difficile–associated disease.

Rifaximin and other antibiotics belonging to the macrocyclic family are being investigated as alternative therapies for C. difficile–associated disease, Dr. Landelle said. Some studies have shown high rates of C. difficile resistance to rifampin in Europe, but the rate of resistance at her institution was low. In Switzerland, rifamycin antibiotics have been used for decades, but rifaximin is not licensed for the treatment of hepatic encephalopathy, diarrhea, and traveler’s diarrhea or for prophylaxis in patients undergoing GI surgery, which may explain the low rate of resistance there.

The study excluded patients with prior episodes of C. difficile–associated disease, patients being treated with metronidazole, and patients with septic arthritis.

Dr. Landelle did not provide her financial disclosures.

SAN FRANCISCO – The addition of rifampin to long-term antibiotic regimens significantly lowers the risk for Clostridium difficile–associated colitis in patients being treated for osteoarticular infections.

The retrospective cohort study comprised 393 treatment episodes – 55% of them for infections subsequent to arthroplasty – among patients admitted to a Swiss orthopedic surgery unit from 1996 to 2012. The ribotype 027 was not endemic in the region.

The 42% of patients who were treated with combination therapy that included oral rifampin (600 mg/day) were significantly less like to develop C. difficile colitis despite being on the antibiotics for a median of 63 days (ranging from 20-294 days), Caroline Landelle, Pharm.D., Ph.D. and her associates reported at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Rifampin use was inversely associated with C. difficile colitis, with an adjusted hazard ratio of 0.18, Dr. Landelle reported in a poster presentation.

In general, longer duration of antibiotics treatment was associated with C. difficile colitis, with an adjusted hazard ratio of 1.01, said Dr. Landelle of the University of Geneva.

Factors not associated with colitis risk (either positively or negatively) included the use of antianaerobic antibiotics (in 38% of patients), treatment with intravenous vancomycin (in 45%, for a median of 13 days), age, or sex.

Fourteen patients (4%) developed symptomatic C. difficile colitis after a median of 14 days of antibiotic treatment (ranging from 8-193 days). Of these, six patients were on vancomycin (43%) and two patients were receiving rifampin (14%) prior to development of the colitis, Dr. Landelle reported at the meeting, sponsored by the American Society for Microbiology.

"C. difficile colitis was rare despite long-term antibiotic use among patients with osteoarticular infection. In contrast to intravenous vancomycin, combination antibiotic therapy with oral rifampin might protect against C. difficile–associated colitis," the investigators suggested.

The cohort had a median age of 69 years; 41% was female, and 31% of patients were immunosuppressed.

Of the 401 microorganisms isolated from the osteoarticular infections, 32% were methicillin-sensitive Staphylococcus aureus, 16% were methicillin-resistant S. aureus, 17% each were coagulase-negative Staphylococcus or gram-negative bacilli, and 18% were other organisms.

The investigators hypothesized that combination therapy with rifampin or derivative medications might protect against C. difficile colitis because very few cases have been reported of rifampin-associated pseudomembranous colitis, and patients undergoing treatment with long-term antibiotic combination therapy for osteoarticular infections rarely develop symptomatic C. difficile–associated disease.

Rifaximin and other antibiotics belonging to the macrocyclic family are being investigated as alternative therapies for C. difficile–associated disease, Dr. Landelle said. Some studies have shown high rates of C. difficile resistance to rifampin in Europe, but the rate of resistance at her institution was low. In Switzerland, rifamycin antibiotics have been used for decades, but rifaximin is not licensed for the treatment of hepatic encephalopathy, diarrhea, and traveler’s diarrhea or for prophylaxis in patients undergoing GI surgery, which may explain the low rate of resistance there.

The study excluded patients with prior episodes of C. difficile–associated disease, patients being treated with metronidazole, and patients with septic arthritis.

Dr. Landelle did not provide her financial disclosures.