CDAD is a unique hospital infection that occurs almost entirely in patients who have received previous antimicrobial treatment. Anaerobic gut flora are crucial to colonization resistance, so any disruption of the normal colonic flora (through illness, therapeutic procedures, or, most commonly, antibiotic use) is essential to the pathogenesis of C. difficile infection.
The association of CDAD with antibiotic use is significant. Early attention in the 1970s focused on clindamycin but later on (1980s, 1990s, and continuing today), the cephalosporins, especially third-generation, and broad-spectrum penicillins (e.g., amoxicillin/ampicillin) were also implicated.
The risk of CDAD is increased if C. difficile is resistant to the particular antimicrobial. In the case of clindamycin, C. difficile resistance is variable. The risk of infection due to a clindamycin-resistant strain increases with the use of the drug. For the third-generation cephalosporins, C. difficile is universally resistant; thus, any toxigenic strain is capable of causing CDAD during cephalosporin use. Other less commonly implicated antibiotics are macrolides, e.g., erythromycin, azithromycin, and clarithromycin. However, prolonged courses of any antibiotic will increase the risk of disease. Even those antibiotics used to treat colitis (e.g., metronidazole) have sometimes been reported to cause CDAD.
The fluoroquinolones have been in use since the 1980s. Ciprofloxacin was approved in 1987, but it is only in recent years with the emergence of the epidemic strain BI/NAP1/027, which is resistant to the fluoroquinolones, that this class of drugs has been implicated in C. difficile disease. Fluoroquinolones were initially considered to be low risk but their use has been increasing, both with hospital inpatients and in the community, and fluoroquinolones are now implicated as a risk factor for C. difficile infection. The newer fluoroquinolones (e.g., gatifloxacin, moxifloxacin) have better activity against anaerobes, but poor in vitro activity against C. difficile, thus increasing the likelihood of CDAD. The CDC now recommends that all fluoroquinolones, as a class, be used sparingly as each poses an increased risk for CDAD.
