Genotypic and phenotypic analysis of Clostridium difficile correlated with previous antibiotic exposure

To analyze Clostridium difficile susceptibility results and genotypes in relation to antibiotic exposures that precipitated C. difficile-associated diarrhea (CDAD), we examined 83 nosocomial C. difficile isolates recovered at a tertiary care center in Boston, Massachusetts. MICs were determined by E-test methodology using modified Brucella agar. Isolates were genotyped by pulsed-field gel electrophoresis and restriction enzyme analysis. Antibiotic susceptibilities were: ciprofloxacin (0%), clindamycin (59%), trovafloxacin (63%), ceftriaxone (73%), piperacillin/tazobactam (100%), metronidazole (100%), and vancomycin (100%). The two most common strain groups, isolated from a total of 33 patients, were much more likely to be resistant to clindamycin, erythromycin, and trovafloxacin than other strain groups [79% (26 of 33) versus 2% (1 of 50), respectively]. Clindamycin exposure was strongly associated with CDAD caused by isolates that exhibited multiple resistance to clindamycin, erythromycin, and trovafloxacin (prevalence odds ratio, 4.2; 95% confidence interval, 1.1-16.8), whereas other antimicrobials did not yield significant associations. Resistance of specific C. difficile strains to clindamycin and other antimicrobial agents may contribute to their hospital dissemination and explain, in part, the propensity of clindamycin to trigger nosocomial outbreaks.