Gram-negative bacilli resistant to third-generation cephalosporins: βMactamase characterization and susceptibility to Sch 34343.

We studied 192 recent clinical isolates, comprising six species of Gram-negative bacilli resistant either to cefotaxime or latamoxef (Moxalactam), from several hospitals. All isolates were resistant to several other third-generation cephalosporins or a monobactam. Two to five types of chromosomal β-lactamases, as defined by isoelectric focusing, were readily identified in each species. Isolates of Citrobacter, Enterobacter and Serratia produced higher levels of chromosomal β-lactamase than corresponding cefotaxime-susoeptible strains. In addition, 20 of 57 produced one or two plasmid-determined β-lactamases, TEM-1, OXA-2, or a novel enzyme, OHIO-1. The penem and carbapenem antibiotics, Sch 34343 and imipenem, were more active than cefotaxime, ceftazidime, ceftriaxone, latamoxef and aztreonam against isolates of Acinetobacter, Citrobacter, Ent. aerogenes, Ent. cloacae and Morganella, whereas imipenem, ceftazidime, and aztreonam were more active against Serratia isolates. The addition of plasmid-determined β-lactamase increased resistance to piperacillin, cefoperazone and cefamandole but not to cefotaxime, ceftazidime, ceftriaxone, latamoxef, aztreonam, Sch 34343, or imipenem. Of 24 strains susceptible to aminoglycosides, none produced a plasmid-determined β-lactamase, whereas 20 were found among the 33 strains resistant to aminoglycosides.Resistance of clinical isolates to newer β-lactams appears to be due primarily to a high level of chromosomal cepahalosporinase present without inducing agents. The plasmid-determined β-lactamases, TEM-1 and OHIO-1, contributed little to resistance to most of the newer β-lactams but were strongly associated with aminoglycoside resistance in these selected isolates. The greater in-vitro efficacy of the penem and carbapenem antibiotics, Sch 34343 and imipenem, against most of these isolates makes them promising candidates as first line agents against these pathogens. [ABSTRACT FROM PUBLISHER]