High Frequency of Rifampin Resistance Identified in an EpidemicClostridium difficileClone from a Large Teaching Hospital

Abstract

Background Rifampin is used as adjunctive therapy for Clostridium difficile–associated disease, and the drug’s derivative, rifaximin, has emerged as an attractive antimicrobial for treatment of C. difficile–associated disease. Rifampin resistance in C. difficile strains has been reported to be uncommon. Methods We examined the prevalence of rifampin resistance among 470 C. difficile isolates (51.1% during 2001–2002 and 48.9% during 2005) from a large teaching hospital. Rifampin sensitivity was performed using E-test. The epidemic BI/NAP1 C. difficile clone was identified by tcdC genotyping and multilocus variable number of tandem repeats analysis. A 200–base pair fragment of the rpoB gene was sequenced for 102 isolates. Data on rifamycin exposures were obtained for all patients. Results Rifampin resistance was observed in 173 (36.8%) of 470 recovered isolates and 167 (81.5%) of 205 of epidemic clone isolates (P < .001). Six rpoB genotypes were associated with rifampin resistance. Of 8 patients exposed to rifamycins, 7 had rifampin-resistant C. difficile, compared with 166 of 462 unexposed patients (relative risk, 2.4; 95% confidence interval, 1.8–3.3). Conclusions Rifampin resistance is common among epidemic clone C. difficile isolates at our institution. Exposure to rifamycins before the development of C. difficile–associated disease was a risk factor for rifampin-resistant C. difficile infection. The use of rifaximin may be limited for treatment of C. difficile–associated disease at our institution.

Divergent Rifamycin Susceptibilities of Clostridium difficile Strains in Canada and Italy and Predictive Accuracy of Rifampin Etest for Rifamycin Resistance

“…Interestingly, the H502N mutation has been associated with intermediate resistance to rifamycins, but never to high-level resistance (6, 18), as we found, which may indicate a separate mechanism of resistance in C. difficile. These SLPs in the rpoB gene are conserved in many genera of rifamycin-resistant bacteria, as demonstrated by sequence alignments (6,16,18).…”

“…The method described by S. R. Curry et al (6) was used to identify the rpoB mutations in strains resistant to RIF. Briefly, primers CDrpoB2F and CDrpoB2R were used to amplify a 200-bp region of the rpoB gene known to contain point mutations associated with resistance to RIF.…”

“…Resistance to the rifamycin class of antibiotics has been putatively linked to 8 SLPs in the rpoB gene of the RNA polymerase locus (6,18) and another 12 SLPs in the rifamycin binding pocket (3). We identified 2 mutations, S488P and S498T, in the rpoB gene that had not been previously described in C. difficile, although a different mutation at S488 (S488T) has been described.…”

Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections

“…In three small series, a total of 16 of 20 patients had no further recurrences when treated with 2 weeks of rifaximin aft er a 2-week course of vancomycin ( 88 -90 ); a recently published RCT of this regimen did not fi nd a decrease in documented CDI recurrences with rifaximin ( 91 ). Moreover, high-level resistance to rifampin is a concern and should limit its use ( 92 ). Summary of the evidence.…”

Rifaximin for the treatment of acute infectious diarrhea

“…In one institution, approximately 81% of the C. difficile isolates were found to be resistant to rifampin [Curry et al 2009]. In addition, the paucity of double-blind RCTs still makes physicians hesitate to prescribe rifaximin for the treatment of patients with CDI.…”