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Antimicrobial Agents and Chemotherapy, November 2008, p. 3909-3914, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.00622-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Prevalence and Mechanisms of Broad-Spectrum β-Lactam Resistance in Enterobacteriaceae: a Children's Hospital Experience{triangledown}

Xuan Qin,1,3* Danielle M. Zerr,2,3 Scott J. Weissman,2,3 Janet A. Englund,2,3 Donna M. Denno,2,3 Eileen J. Klein,2,3 Phillip I. Tarr,4 Justin Kwong,1 Jennifer R. Stapp,1 Luis G. Tulloch,3 and Emmanouil Galanakis1

Microbiology Laboratory, Department of Laboratory Medicine, Children's Hospital and Regional Medical Center, Seattle, Washington,1 Department of Pediatrics, University of Washington,2 University of Washington School of Medicine, Seattle, Washington,3 Departments of Pediatrics and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri4

Received 12 May 2008/ Returned for modification 8 July 2008/ Accepted 22 August 2008

The objective of this study was to investigate the trends and patterns of resistance in β-lactamase-producing members of the family Enterobacteriaceae in a children's hospital over a 9-year period (1999 to 2007). Clinically significant isolates of the Enterobacteriaceae were screened for patterns of broad-spectrum resistance to β-lactams. The strains likely to be resistant were subsequently confirmed by an inhibitor-based disc test. The plasmid-mediated resistance determinants in these isolates were identified by PCR and by in vitro transformation, which successfully reproduced the AmpC phenotype unrestricted by the species of the host organisms. Among 8,048 Enterobacteriaceae isolates belonging to the four chromosomal ampC-negative or -nonfunctional genera, 86 (1.07%) isolates (56 Escherichia coli isolates, 22 Klebsiella species isolates, 1 Proteus mirabilis isolate, and 7 Salmonella species isolates) exhibited broad-spectrum β-lactam resistance patterns. These organisms collectively produced three classes of β-lactamases, including class A extended-spectrum β-lactamases (n = 47), class C or AmpC β-lactamases (n = 36, including 4 isolates that produced both class A and class C enzymes), and class A or B carbapenem-hydrolyzing β-lactamases (n = 3). The proportion increased from 0.46% during the first 3 years to 1.84% during the last 3 years (relative risk [RR], 4.04; 95% confidence interval [CI], 2.28 to 7.42; P < 0.001). The increase was mainly due to the emergence of a plasmid-mediated blaCMY-2 β-lactamase, the incidence of which increased from 0.11% during the first 3 years to 0.96% during the last 3 years (RR, 9.11; 95% CI, 2.76 to 30.1; P = 0.001). Class A-type resistance increased slightly during the study period, from 0.35% during the first 3 years to 0.85% during the last 3 years (RR, 2.42; 95% CI, 1.15 to 5.07; P = 0.02). A Proteus mirabilis strain was documented to possess a novel blaDHA determinant. Of special concern, three carbapenemase-producing isolates were identified between 2003 and 2006. The infections caused by resistant isolates of the Enterobacteriaceae mainly affected hospitalized patients with underlying conditions; however, 19 (22%) episodes were of community onset in otherwise well children. The rate of resistance to broad-spectrum β-lactams among isolates of the Enterobacteriaceae is increasing in children in both hospital- and community-acquired settings, and the resistance is driven largely by plasmid-mediated AmpC β-lactamases. These data have important implications for empirical antimicrobial strategies targeting serious pediatric infections. Further study of this problem is warranted.

* Corresponding author. Mailing address: Microbiology Laboratory, Department of Laboratory Medicine, 6P-1, Children's Hospital and Regional Medical Center, 4800 Sand Point Way, NE, Seattle, WA 98105-0371. Phone: (206) 987-2586. Fax: (206) 987-3840. E-mail: xuan.qin{at}seattlechildrens.org

{triangledown} Published ahead of print on 2 September 2008.

Antimicrobial Agents and Chemotherapy, November 2008, p. 3909-3914, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.00622-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jacoby, G. A. (2009). AmpC {beta}-Lactamases. Clin. Microbiol. Rev. 22: 161-182 [Abstract] [Full Text]  


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