Bloodstream infections by extended-spectrum beta-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 beta-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.

FIG. 1.

Dendrograms of ESBL-producing K. pneumoniae (A) and E. coli (B) strains based on PFGE results. Twenty-nine strains of K. pneumoniae and nine strains of E. coli were included in the analysis. For PFGE analysis, the chromosomal DNA was digested with XbaI and electrophoresed in 1% agarose. The strains were clustered by the unweighted pair group method with arithmetic averages (UPGMA). The scale indicates the percentage of genetic similarity. The molecular size marker is a bacteriophage lambda ladder (Bio-Rad Laboratories, Inc.). The strain designations indicate the species (Kp, K. pneumoniae; Ec, E. coli), patterns of production of β-lactamases (A to K, as grouped in Table 6), year of isolation, and strain number.