Cephalosporin resistance in Pseudomonas aeruginosa, with special reference to the proposed trapping of antibiotics by beta-lactamase.

Resistance of Pseudomonas aeruginosa strains to newer cephalosporins is often associated with stable derepression of synthesis of the chromosomal beta-lactamase. Similar resistance is developed by enzyme inducible (i.e. normal) strains in response to beta-lactamase inducers. By comparing the responses of otherwise isogenic P. aeruginosa beta-lactamase inducibility mutants to antipseudomonal cephalosporins alone or in combination with potent beta-lactamase inducers we confirmed that resistance to cefotaxime, ceftriaxone, cefoperazone, and ceftazidime and latamoxef was caused by beta-lactamase action. The low-level resistance to carbenicillin and cefsulodin which was exhibited by some fully beta-lactamase derepressed strains was not confirmed to be beta-lactamase determined and may have reflected concurrent target or permeability changes. The mechanism whereby the enzyme protected the cell against cefotaxime and ceftriaxone was also investigated. These agents are reportedly stable to the enzyme and some workers have suggested that resistance entails their being trapped rather than hydrolysed. However, the use of a novel model of cellular beta-lactamase function indicated that a hydrolytic resistance mechanism remained likely.