Clindamycin, cephalosporins, fluoroquinolones, and Clostridium difficile-associated diarrhea: this is an antimicrobial resistance problem.

Clostridium difficile–associated diarrhea (CDAD) is a unique hospital infection that occurs almost entirely in patients who have received previous antimicrobial treatment. Although not conclusively proven, the normal gastrointestinal flora is presumably disrupted by antimicrobials, which, in turn, enables ingested spores of toxigenic C. difficile to colonize the colon, produce toxins, and cause CDAD. Epi-demiologic evidence suggests that specific antimicrobials and classes of antimicro-bials are not created equal in terms of CDAD risk [1]. Two risks for CDAD are of interest because of how they relate to antimicrobial use: the relative risk of CDAD associated with use of a specific antimicrobial, and the attributable risk of CDAD in a particular population. Attributable risk incorporates both the relative risk of an antimicrobial and the frequency with which that drug is used in the population. Clindamycin was the highest-risk agent for CDAD in the 1970s, but its use has decreased in US and European hospitals , with a resultant reduction in attributable risk of antibiotic-associated diarrhea and CDAD [2]. By the late 1980s and through the 1990s, cephalosporin anti-microbials, particularly those of the second and third generation, such as cefu-roxime, cefotaxime, ceftazidime, and ceftriaxone, had become the agents with the highest relative risk and highest attributable risk of CDAD because of their frequent use in hospitals [1]. The risk of antimicrobial-associated CDAD is increased if C. difficile is resistant to the antimicrobial [3]. For clindamycin, C. difficile resistance is variable, and risk of CDAD associated with a clindamycin-resistant organism is increased in patients receiving clindamycin [3]. For the third-generation cephalosporins, C. difficile resistance is universal, and presumably any toxigenic C. difficile organism is capable of causing CDAD during cephalosporin administration. The good news has been that CDAD rates have markedly decreased when the use of clindamycin or third-generation cephalosporins has been reduced in hospitals where these agents were associated with high CDAD rates [3, 4]. More recently, the saga of CDAD risk and antimicrobial use has been extended to the fluoroquinolone class, as shown by Gaynes et al. [5] in this issue of Clinical Infectious Diseases and by others [6–8]. Fluoroquinolones had been considered relatively low-risk agents for CDAD on the basis of a number of observations with regard to ciprofloxacin that included poor anaerobic activity, failure of fecal emulsions treated with ciprofloxacin to support growth of C. difficile in vitro (compared with clindamycin-treated emulsions), and lack of observed CDAD or C. difficile …