Beta-lactamase enzymes produced by gram-negative bacilli were identified before the first beta-lactam antibiotics were used to treat infections. As these enzymes adapted to available beta-lactam agents, newer beta-lactam agents were developed. Development and widespread use of the oxyimino-cephalosporins led to the emergence of extended-spectrum beta-lactamase enzymes that hydrolyze the penicillins, extended-spectrum cephalosporins, and aztreonam. There are now over 200 recognized ESBLs in a variety of gram-negative bacilli conferring resistance to penicillins, cephalosporins, a monobactam, and even carbapenems. The emergence of these enzymes is associated with poor patient outcomes, increased total health care costs, and more carbapenem use. Carbapenems should be selected judiciously to optimize outcomes while preventing further selection of extended-spectrum beta-lactamase resistance.
Jacoby GA, Munoz-Price LSThe new beta-lactamases. New Engl J Med. 2005 ;352:380-391.
3.
Medeiros AAEvolution and dissemination of beta-lactamases accelerated by generations of beta-lactam antibiotics. Clin Infect Dis. 1997;24:S19-S45.
4.
Nathisuwan S. , Burgess DS, Lewis JSExtended-spectrum beta-lactamases: epidemiology, detection, and treatment. Pharmacotherapy. 2001;21:920-928.
5.
Nicasio AM, Kuti JL, Nicolau DPThe current state of multi-drug resistant gram-negative bacilli in North America . Pharmacotherapy. 2008;28:235-249.
6.
Bradford PAExtended-spectrum beta-lactamases in the 21st Century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev. 2001;14:933-951.
Bush K.New beta-lactamases in gram-negative bacteria: diversity and impact on the selection of antimicrobial therapy. Clin Infect Dis . 2001;32:1085-1089.
9.
Livermore DM , Woodford N.The beta-lactamase threat in Enterobacteriaceae, Pseudomonas and Acinetobacter. Trends in Microbiol. 2006;14:413-420.
10.
Nicolau DPOptimizing the use of carbapenems in the face of increasing gram-negative resistance. Formulary. 2007;42(suppl):1-15.
11.
Pitout JDD , Nordmann P., Laupland KB, Poirel L.Emergence of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) in the community. J Antimicrob Chemother. 2005;56:52-59.
12.
Rodriguez-Bano J., Navarro MD, Romero L., et al. Epidemiology and clinical features of infections caused by extended-spectrum beta-lactamase-producing Escherichia coli in nonhospitalized patients. J Clin Microbiol . 2004;42:1089-1094.
13.
Bush K., Jacoby GA, Medeiros AAA functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother. 1995;39:1211-1233.
14.
Lautenbach E., Patel JB, Bilker WB, Edelstein PH, Fishman NOExtended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes. Clin Infect Dis. 2001;32:1162-1171.
15.
Rossolini GM , D'Andrea MM, Mugnaioli C.The spread of CTX-M-type extended-spectrum beta-lactamases. Clin Microbiol Infect. 2008 ;14:33-41.
16.
Yang K., Guglielmo BJDiagnosis and treatment of extended-spectrum and AmpC beta-lactamase-producing organisms. Ann Pharmacother. 2007;41:1427-1435.
17.
Schwaber MJ , Venezia SN, Schwartz D., Carmeli Y.High levels of antimicrobial coresistance among extended-spectrum beta-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2005;49: 2137-2139.
18.
Livermore D.Tigecycline: what it is and where should it be used? J Antimicrob Chemother. 2005;56:611-614.
19.
Karabinis A. , Paramythiotou E., Mylona-Petropoulou D., et al. Colistin for Klebsiella pneumoniae-associated sepsis. Clin Infect Dis. 2004;38:e7-e9.
20.
Clark NM, Patterson J., Lynch JPAntimicrobial resistance among gram-negative organisms in the intensive care unit. Curr Opin Crit Care. 2003;9:413-423.
21.
Walther-Rasmussen J., Hoiby N.Class A carbapenemases. J Antimicrob Chemother. 2007;60:470-482.
22.
Queenan AM, Bush K.Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev. 2007;20: 440-458.
23.
Evans HL, Lefrak SN, Lyman J., et al. Cost of gram-negative resistance. Crit Care Med. 2007;35:89-95.
24.
Lee SY, Kotapati S., Kuti JL, Nightingale CH, Nicolau DPImpact of extended-spectrum beta lactamase-producing Escherichia coli and Klebsiella species on clinical outcomes and hospital costs: a matched cohort study. Infect Control Hosp Epidemiol. 2006 ;27:1226-1232.
25.
Schwaber MJ, Navon-Venezia S., Kaye KS, Ben-Ami R., Schwartz D., Carmeli Y.Clinical and economic impact of bacteremia with extended-spectrum beta-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2006;50:1257-1267.
26.
Hyle EP, Lipworth AD, Zaoutis TE, Nachamkin I., Bilker WB, Lautenbach E.Impact of inadequate initial antimicrobial therapy on mortality in infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae . Arch Intern Med. 2005;165:1375-1380.
