Dissemination of Metallo-â-Lactamase Gene blaIMP-4 Among Gram-Negative Pathogens in a Clinical Setting
Dissemination of Metallo-β-Lactamase Gene blaIMP-4 Among Gram-Negative Pathogens in a Clinical Setting
Abstract & Commentary
By Robert Muder, MD, Hospital Epidemiologist, Pittsburgh VA Medical Center, Pittsburgh, Section Editor, Hospital Epidemiology, is Associate Editor for Infectious Disease Alert.
Dr. Muder does research for Aventis and Pharmacia.
Synopsis: Investigators reported finding the presence of a metallo-β-lactamase gene mediating resistance to multiple β-lactam antibiotics, including carbapenems, among multiple species of Gram-negative pathogens isolated from a single hospital in Australia. Epidemiologic and molecular evidence suggested horizontal transmission of a mobile genetic element.
Source: Peleg AY, et al. Dissemination of Metallo-β-Lactamase Gene blaIMP-4 Among Gram-Negative Pathogens in a Clinical Setting in Australia. Clin Infect Dis. 2005;41:1549-1556.
Metallo-β-Lactamase (MBL) enzymes mediate resistance to multiple β-lactam antibiotics, including carbapenems. Carbapenems are often the agents of last resort against multiply resistant Gram-negative pathogens, as agents of this class of antibiotics are resistant to the action of AmpC and extended-spectrum β-lactamases. Acquisition of MBL genes by common nosocomial pathogens could seriously limit available treatment options.
Utilizing the fact that MBL’s require zinc ions for hydrolytic activity, Peleg and colleagues used differential susceptibility to imipenem in the presence of EDTA to detect the MBL phenotype. They then tested nosocomial Gram-negative isolates positive on phenotypic testing for the presence of 2 MBL genetic determinants, blaIMP and blaVIM.
Over a 7-month period, they tested 2100 unique clinical isolates for resistance to multiple b-lactam antibiotics and identified 204. Of these, 20 isolates from 16 patients had the MBL phenotype according to the study definition. Nineteen of these isolates carried the same MBL gene, blaIMP-4. These isolates included 10 Serratia marcescens, 4 Klebsiella pneumoniae, 3 Pseudomonas aeruginosa, 1 Escherichia coli, and 1 Enterobacter cloacae. All of the isolates were resistant to cephalosporins and b-lactam/b-lactamase inhibitor combinations. Susceptibility to carbapenems as determined by automated broth icro-dilution (Vitek) was variable, with MICs of 2 to >8 ug/mL. Most isolates were susceptible to aztreonam. All isolates were hospital acquired, and 14 of the 16 patients could be linked in space and time to the ICU. Seventy-five percent of patients had received a carbapenem before isolation of an MBL bearing strain, and 75% of the isolates were associated with clinical infection.
Commentary
MBL’s were first described as constitutive enzymes mediating resistance to beta-lactams in relatively uncommon Gram negative pathogens such as Stenotrophomonas maltophilia. Unlike the beta-lactamases commonly found in P. aeruginosa and Enterobacteriaceae, MBLs hydrolyze carbapenems, as well as cephalosporins and extended-spectrum penicillins. There have been reports of sporadic detection of MBLs in isolates of P. aeruginosa and Enterobacteriaceae, but these enzymes do not appear to be widely disseminated among these common nosocomial pathogens.
The work by Peleg and colleagues is notable in that an outbreak of MBL-carrying organisms occurred in a single hospital. Even more notable, the outbreak appeared to involve transmission of a mobile genetic element among multiple species, and among different strains of the same species. The evidence for this is compelling. Fourteen of the 16 patients could be epidemiologically linked and the identical MBL gene, blaIMP-4, was detected in 19 of the 20 MBL isolates. In addition, the same class I integron, IntI1, was found in all 19 by PCR.
These findings have disturbing implications for the spread of carbapenem resistance. This MBL gene appears to be readily transferable among species of nosocomial Gram-negative pathogens. Further, it is not reliably detected by standard microbroth dilution techniques. Widespread dissemination of strains carrying these genes may dramatically limit treatment options for nosocomial Gram-negative infections.
Synopsis: Investigators reported finding the presence of a metallo-â-lactamase gene mediating resistance to multiple â-lactam antibiotics, including carbapenems, among multiple species of Gram-negative pathogens isolated from a single hospital in Australia.Subscribe Now for Access
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