Epidemics of diarrhea caused by a clindamycin-resistant strain of Clostridium difficile in four hospitals.

Background: Large outbreaks of diarrhea caused by a newly recognized strain of Clostridium difficile occurred in four hospitals located in different p arts of the United States between 1989 and 1992. Since frequent use of clin damycin was associated with the outbreak in one of the hospitals, we examin ed the resistance genes of the epidemic-strain isolates and studied the rol e of clindamycin use in these outbreaks. Methods: Case-control studies were performed at three of the four hospitals to assess the relation of the use of clindamycin to C. difficile-associate d diarrhea. All isolates of the epidemic strain and representative isolates of other strains identified during each outbreak were tested for susceptib ility to clindamycin. Chromosomal DNA from these representative isolates wa s also analyzed by dot blot hybridization and amplification with the polyme rase chain reaction (PCR) with the use of probes and primers from a previou sly described determinant of erythromycin resistance -- the erythromycin ri bosomal methylase B (ermB) gene -- found in C. perfringens and C. difficile . Results: In a stratified analysis of the case-control studies with pooling of the results according to the Mantel-Haenszel method, we found that the u se of clindamycin was significantly increased among patients with diarrhea due to the epidemic strain of C. difficile, as compared with patients whose diarrhea was due to nonepidemic strains (pooled odds ratio, 4.35; 95 perce nt confidence interval, 2.02 to 9.38; P<0.001). Exposure to other types of antibiotics or hospitalization in a surgical ward was not significantly ass ociated with the risk of C. difficile-associated diarrhea due to the epidem ic strain. All epidemic-strain isolates were highly resistant to clindamyci n (minimal inhibitory concentration, >256 microg per milliliter). DNA hybri dization and PCR analysis showed that all these isolates had an ermB gene, which encodes a 23S ribosomal RNA methylase that mediates resistance to mac rolide, lincosamide, and streptogramin antibiotics. Only 15 percent of the nonepidemic strains were resistant to clindamycin. Conclusions: A strain of C. difficile that is highly resistant to clindamyc in was responsible for large outbreaks of diarrhea in four hospitals in dif ferent states. The use of clindamycin is a specific risk factor for diarrhe a due to this strain. Resistance to clindamycin further increases the risk of C. difficile-associated diarrhea, an established complication of antimic robial use. (N Engl J Med 1999;341:1645-51.) (C) 1999, Massachusetts Medica l Society.