Bloodstream Infections by Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in Children: Epidemiology and Clinical Outcome

Abstract

To determine the epidemiologic features and clinical outcomes of bloodstream infections caused by extended-spectrum ␤-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolates, cases of bacteremia caused by these organisms in children were analyzed retrospectively. Among the 157 blood isolates recovered from 1993 to 1998 at the Seoul National University Children's Hospital, the prevalence of ESBL production was 17.9% among the E. coli isolates and 52.9% among the K. pneumoniae isolates. The commonest ESBLs were SHV-2a and TEM-52. A novel ESBL, TEM-88, was identified. Pulsed-field gel electrophoresis analysis of the ESBL-producing organisms showed extensive diversity in clonality. The medical records of 142 episodes were reviewed. The risk factors for bloodstream infection with ESBL-producing organisms were prior hospitalization, prior use of oxyimino-cephalosporins, and admission to an intensive care unit within the previous month. There was no difference in clinical severity between patients infected with ESBL-producing strains (the ESBL group) and those infected with ESBL-nonproducing strains (the non-ESBL group) at the time of presentation. However, the overall fatality rate for the ESBL group was significantly higher than that for the non-ESBL group: 12 of 45 (26.7%) versus 5 of 87 (5.7%) (P ‫؍‬ 0.001). In a subset analysis of patients treated with extended-spectrum cephalosporins with or without an aminoglycoside, favorable response rates were significantly higher in the non-ESBL group at the 3rd day (6 of 17 versus 33 of 51; P ‫؍‬ 0.035), the 5th day (6 of 17 versus 36 of 50; P < 0.05), and the end of therapy (9 of 17 versus 47 of 50; P < 0.001). In conclusion, the ESBL production of the infecting organisms has a significant impact on the clinical course and survival of pediatric patients with bacteremia caused by E. coli and K. pneumoniae.Escherichia coli and Klebsiella pneumoniae are leading causes of serious infections in neonates, neutropenic cancer patients, and other patients with underlying diseases. These bacteria had been uniformly susceptible to oxyimino-␤-lactam antimicrobials. However, since the initial description of extended-spectrum ␤-lactamase (ESBL) production by K. pneumoniae strains in 1983 (18) and E. coli strains in 1987 (3), strains of E. coli and K. pneumoniae that are resistant to broadspectrum cephalosporins are increasingly being recognized (6, 14). There have been many reports of outbreaks caused by these organisms in cancer centers, pediatric and geriatric wards, and hospitalized nursing home patients. However, epidemiologic descriptions of bloodstream infections caused by ESBL-producing E. coli and K. pneumoniae are limited (32,36), and clinical data regarding treatment are further limited (2,31,35,36). At present, carbapenems are recommended for the treatment of infections caused by ESBL-producing organisms. However, this recommendation is primarily based on the in vitro effect (12), the results of animal experiments (33), and only very limited clinical da...

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