Nosocomial Outbreak of Klebsiella Infection Resistant to Late-Generation Cephalosporins

OBJECTIVE: To describe the epidemiology, antimicrobial susceptibility, and control of widespread ceftazidime-resistant Klebsiella pneumoniae infections in a North American hospital and circumstances that led to delayed detection. DESIGN: A 2-year epidemiologic, microbiologic, and clinical cohort study. SETTING: A 487-bed general hospital in New York City. PATIENTS AND CLINICAL ISOLATES: Patient records were reviewed retrospectively and prospectively. Isolates were obtained from the Clinical Microbiology Laboratory. RESULTS: Four hundred thirty-two isolates of ceftazidime-resistant Klebsiella pneumoniae were recovered during a 19-month study period. The peak incidence reached 17.3% of all Klebsiella isolates. One hundred fifty-five patients were colonized or infected, representing more than 70 per 1000 average daily census. Infections occurred in 39% of patients from whom ceftazidime-resistant Klebsiella was isolated. These included 14 bacteremias and 17 pulmonary infections among 52 infected patients. The outbreak coincided with increasing use of ceftazidime therapy for multiresistant Acinetobacter infections. Reduction in ceftazidime use and barrier precautions markedly reduced the incidence of colonization and infection. Ceftriaxone, ceftizoxime, cefotaxime, and cephamycins were inhibitory, but not bactericidal, against ceftazidime-resistant Klebsiella and appeared effective by routine disc diffusion tests. In contrast, imipenem provided consistent bactericidal activity. Preliminary studies indicated that the outbreak was caused by one or more plasmid-mediated beta lactamases. CONCLUSIONS: Nosocomial ceftazidime-resistant Klebsiella pneumoniae may be resistant to the bactericidal activity of all cephalosporins and cephamycins. Such isolates appear susceptible to cephalosporins other than ceftazidime by routine disc diffusion testing. Ineffective therapy, delayed detection of resistance, and epidemic spread are potential consequences. Imipenem provides consistent bactericidal activity. Ceftazidime restriction and barrier precautions for colonized and infected patients are effective control measures.