Multifocal outbreaks of metallo-beta-lactamase-producing Pseudomonas aeruginosa resistant to broad-spectrum beta-lactams, including carbapenems

Abstract

A total of 3,700 Pseudomonas aeruginosa isolates were collected from 17 general hospitals in Japan from 1992 to 1994. Of these isolates, 132 carbapenem-resistant strains were subjected to DNA hybridization analysis with the metallo-beta-lactamase gene (blaIMP)-specific probe. Fifteen strains carrying the metallo-beta-lactamase gene were identified in five hospitals in different geographical areas. Three strains of P. aeruginosa demonstrated high-level imipenem resistance (MIC, > or = 128 micrograms/ml), two strains exhibited low-level imipenem resistance (MIC, < or = 4 micrograms/ml), and the rest of the strains were in between. These results revealed that the acquisition of a metallo-beta-lactamase gene alone does not necessarily confer elevated resistance to carbapenems. In several strains, the metallo-beta-lactamase gene was carried by large plasmids, and carbapenem resistance was transferred from P. aeruginosa to Escherichia coli by electroporation in association with the acquisition of the large plasmid. Southern hybridization analysis and genomic DNA fingerprinting profiles revealed different genetic backgrounds for these 15 isolates, although considerable similarity was observed for the strains isolated from the same hospital. These findings suggest that the metallo-beta-lactamase-producing P. aeruginosa strains are not confined to a unique clonal lineage but proliferated multifocally by plasmid-mediated dissemination of the metallo-beta-lactamase gene in strains of different genetic backgrounds. Thus, further proliferation of metallo-beta-lactamase-producing strains with resistance to various beta-lactams may well be inevitable in the future, which emphasizes the need for early recognition of metallo-beta-lactamase-producing strains, rigorous infection control, and restricted clinical use of broad-spectrum beta-lactams including carbapenems.

Metallo-?-lactamases: two binding sites for one catalytic metal ion?

“…The structure was obtained from crystals grown at pH 5.6 and showed that a single zinc ion was bound by three histidines, thus confirming the earlier predictions [17,18]. In 1996 carbapenem-resistant strains of Pseudomonas aeruginosa were found to carry the blaIMP gene [31,32]. In the same year a crystal structure of CcrA was published [12].…”

An epidemiological study of the susceptibility and frequency of multiple-drug-resistant strains of Pseudomonas aeruginosa isolated at medical institutes nationwide in Japan

“…In many cases, however, the activity of the antibacterial agents against P. aeruginosa in vitro was lower than that against other Gram-negative bacilli. Furthermore, P. aeruginosa rapidly developed resistance to these antibacterial agents via diverse and complex mechanisms, 3,4,[8][9][10]15 as mentioned above, e.g., by the formation of a biofilm 11 or by the development of changes in the surface structures, 4,16 which decreased the antibiotics' ability to permeate the intracellular membranes. For the successful treatment of P. aeruginosa infection, it is urgent to have adequate evaluation of the efficacy of currently available agents that are effective against P. aeruginosa, and to have knowledge of the current status of the drug resistance.…”

“…While many antibacterial agents of various families effective against P. aeruginosa have been introduced for clinical use, P. aeruginosa has rapidly developed resistance to these antibacterial agents, via various mechanisms. [8][9][10] Furthermore, the antibacterial activity of the available agents against P. aeruginosa is therapeutically inferior as compared to that against other organisms. Thus, further advances in chemotherapy against P. aeruginosa infection would be highly desirable.…”

Relationship between the usage of carbapenem antibiotics and the incidence of imipenem-resistant Pseudomonas aeruginosa

“…6 According to surveys of MBL-producing P. aeruginosa carried out in 1996 and 1997 in general hospitals in Japan, the isolation rate was 1.3% of P. aeruginosa strains. 7 However, the prevalence of these strains in smallscale hospitals is unknown.…”