RESUMEN
BACKGROUND: Large outbreaks of diarrhea caused by a newly recognized strain of Clostridium difficile occurred in four hospitals located in different parts of the United States between 1989 and 1992. Since frequent use of clindamycin was associated with the outbreak in one of the hospitals, we examined the resistance genes of the epidemic-strain isolates and studied the role 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-associated diarrhea. All isolates of the epidemic strain and representative isolates of other strains identified during each outbreak were tested for susceptibility to clindamycin. Chromosomal DNA from these representative isolates was also analyzed by dot blot hybridization and amplification with the polymerase chain reaction (PCR) with the use of probes and primers from a previously described determinant of erythromycin resistance - the erythromycin ribosomal 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 use 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 percent 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 associated with the risk of C. difficile-associated diarrhea due to the epidemic strain. All epidemic-strain isolates were highly resistant to clindamycin (minimal inhibitory concentration, >256 microg per milliliter). DNA hybridization and PCR analysis showed that all these isolates had an ermB gene, which encodes a 23S ribosomal RNA methylase that mediates resistance to macrolide, 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 clindamycin was responsible for large outbreaks of diarrhea in four hospitals in different states. The use of clindamycin is a specific risk factor for diarrhea due to this strain. Resistance to clindamycin further increases the risk of C. difficile-associated diarrhea, an established complication of antimicrobial use.
Asunto(s)
Antibacterianos/efectos adversos , Clindamicina/efectos adversos , Clostridioides difficile/clasificación , Diarrea/epidemiología , Diarrea/microbiología , Brotes de Enfermedades , Enterocolitis Seudomembranosa/epidemiología , Estudios de Casos y Controles , Clostridioides difficile/genética , Clostridioides difficile/aislamiento & purificación , Infección Hospitalaria/inducido químicamente , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Diarrea/inducido químicamente , Farmacorresistencia Microbiana/genética , Enterocolitis Seudomembranosa/inducido químicamente , Enterocolitis Seudomembranosa/microbiología , Hospitales , Humanos , Pruebas de Sensibilidad Microbiana , Estados Unidos/epidemiologíaRESUMEN
During an outbreak of diarrhea in a general hospital in 1992, 166 Clostridium difficile isolates from 102 patients were typed by restriction enzyme analysis (REA), arbitrarily primed PCR (AP-PCR), and protein profile analysis (PP) techniques. A total of 18 types and 5 subtypes were identified by REA, 32 types were identified by AP-PCR, and 9 types were identified by PP. Analysis of the data indicated the presence of a predominant strain among 76, 75, and 84% of the isolates by REA, AP-PCR, and PP, respectively. Subsequently, 45 C. difficile isolates which had been collected in 1990 from 33 patients in the same hospital following a significant increase in the number of cases of diarrhea caused by C. difficile were studied by REA, AP-PCR, and PP typing techniques. Thirteen types and one subtype were identified by REA, 12 types were identified by AP-PCR, and 5 types were identified by PP. As with the isolates from 1992, a dominant strain was identified. This strain was represented by 53, 64, and 70% of the total number of isolates when the strains were typed by REA, AP-PCR, and PP, respectively. Every isolate (210 of 211) from both 1990 and 1992 that was available for typing was typeable by all three methods. Furthermore, the same dominant strain was identified in both 1990 and 1992 by each method. This study demonstrates that each of the three typing methods can be useful in epidemiologic investigations of C. difficile outbreaks and that one strain can be dominant in an institution over a number of years.
Asunto(s)
Clostridioides difficile/genética , Infección Hospitalaria/epidemiología , Brotes de Enfermedades/estadística & datos numéricos , Enterocolitis Seudomembranosa/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Clostridioides difficile/clasificación , Clostridioides difficile/aislamiento & purificación , Infección Hospitalaria/microbiología , Enterocolitis Seudomembranosa/microbiología , Enterocolitis Seudomembranosa/mortalidad , Heces/microbiología , Femenino , Hospitales Generales , Humanos , Incidencia , Tiempo de Internación , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Prohibitinas , Mapeo Restrictivo/métodos , Estaciones del Año , Serotipificación/métodos , Virginia/epidemiologíaRESUMEN
Fifty-eight vancomycin-resistant enterococcal isolates were obtained from two patients over 9 weeks. Numerous pulsed-field gel electrophoresis fingerprinting types were isolated from each patient. By PCR, all isolates were vanA+. However, many isolates from patient B were found to lack vanA by hybridization. Our results demonstrate the importance of examining multiple isolates, especially from patients who are at high risk of infection.
Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/genética , Ligasas de Carbono-Oxígeno/genética , Enterococcus faecalis/genética , Enterococcus faecium/genética , Infecciones por Bacterias Grampositivas/microbiología , Vancomicina/farmacología , Anciano , Farmacorresistencia Microbiana/genética , Electroforesis en Gel de Campo Pulsado , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecalis/aislamiento & purificación , Enterococcus faecium/efectos de los fármacos , Enterococcus faecium/aislamiento & purificación , Humanos , Cuidados a Largo Plazo , Masculino , Persona de Mediana Edad , Hibridación de Ácido Nucleico , Plásmidos/genética , Reacción en Cadena de la Polimerasa/métodosRESUMEN
The prevalence of, and clinical risk factors associated with, vancomycin-resistant enterococcal colonization were investigated in patients suspected of having Clostridium difficile infection. Stools submitted for C difficile cytotoxin testing were screened for vancomycin-resistant enterococci (VRE). Isolates were speciated and characterized further by antibiotic susceptibility testing, DNA fingerprinting, and DNA:DNA hybridization for detection of specific vancomycin resistance genes. Of the 79 evaluable patients identified during a 3-month period, 16.5% were VRE-positive. The VRE isolates were genetically heterogeneous, although all carried the vanA gene. DNA fingerprinting data suggest that patient-to-patient transmission occurred, implicating colonized patients as potential reservoirs for VRE transmission. A positive C difficile cytotoxin assay and diabetes mellitus were the only identifiable risk factors associated with VRE colonization. Patients at risk for C difficile infection therefore may serve as reservoirs for VRE.