nitrocefin and Pseudomonas-Infections

GES-13 beta-lactamase, a novel GES variant possessing Lys-104 and Asn-170, was identified in Pseudomonas aeruginosa. bla(GES-13) was the single gene cassette of a class 1 integron probably located in the chromosome. GES-13 efficiently hydrolyzed broad-spectrum cephalosporins and aztreonam. Imipenem was a potent inhibitor of GES-13 but was not hydrolyzed at measurable rates.

Topics: Anti-Bacterial Agents; Aztreonam; beta-Lactamases; beta-Lactams; Cephalosporins; Genetic Variation; Humans; Integrons; Microbial Sensitivity Tests; Molecular Sequence Data; Pseudomonas aeruginosa; Pseudomonas Infections; Sequence Analysis, DNA

A detailed biochemical characterization of the Pseudomonas aeruginosa VIM-11 metallo-beta-lactamase (MbetaL) is reported. The only substitution differentiating VIM-11 from VIM-2 (N165S) promoted a slightly improved catalytic efficiency of the former on 3 out of 12 substrates, notably the bulky cephalosporins. Thus, MbetaL-mediated resistance also may be modulated by remote mutations.

Topics: beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Binding Sites; Escherichia coli; Humans; Kinetics; Microbial Sensitivity Tests; Models, Molecular; Plasmids; Pseudomonas aeruginosa; Pseudomonas Infections

Since their initial description 2 decades ago, MexCD-OprJ-overproducing efflux mutants of Pseudomonas aeruginosa (also called nfxB mutants) have rarely been described in the clinical setting. Screening of 110 nonreplicate clinical isolates showing moderate resistance to ciprofloxacin (MIC from 0.5 microg/ml to 4 microg/ml) yielded only four mutants (3.6%) of that type harboring various alterations in the repressor gene nfxB. MexCD-OprJ upregulation correlated with an increased resistance to ciprofloxacin, cefepime, and chloramphenicol in most of the clinical strains, concomitant with a higher susceptibility to ticarcillin, aztreonam, imipenem, and aminoglycosides. Evidence was obtained that this increased susceptibility to aminoglycosides results from the impaired activity of efflux pump MexXY-OprM. Furthermore, MexCD-OprJ upregulation was found to impair bacterial growth and to have a strain-specific, variable impact on rhamnolipid, elastase, phospholipase C, and pyocyanin production. Review of patient files indicated that the four nfxB mutants were responsible for confirmed cases of infection and emerged during long-term therapy with ciprofloxacin. Taken together, these data show that, while rather infrequent among P. aeruginosa strains with low-level resistance to ciprofloxacin, MexCD-OprJ-overproducing mutants may be isolated after single therapy with fluoroquinolones and may be pathogenic.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; Base Sequence; Ciprofloxacin; DNA Primers; DNA-Binding Proteins; DNA, Bacterial; Drug Resistance, Bacterial; Female; Genes, Bacterial; Humans; Male; Membrane Proteins; Membrane Transport Proteins; Middle Aged; Molecular Sequence Data; Mutation; Pseudomonas aeruginosa; Pseudomonas Infections; Transcription Factors; Virulence