Response of chemostat cultures of Pseudomonas aeruginosa to carbapenems and other β-lactams

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Abstract
Cultures of Pseudomonas aeruginosa were grown at different rates in a chemostat and challenged continuously or intermittently with ceftazidime, imipenem, mero-penem or piperacillin. The killing rate was related to the bacterial growth rate; fast-growing cells being killed more rapidly than slow-growing ones. Mutants that were stably derepressed (i.e. constitutive) for chromosomal β-lactamase expression were selected when a β-lactamase inducible (i.e. typical) strain was challenged with ceftazidime or piperacillin. Addition of the β-lactamase inhibitor tazobactam to piperacillin did not prevent selection. There was a lag of c. 24–48 h post-challenge before totally derepressed mutants were detectable. Once selected, the derepressed organisms were stable and were not outgrown by inducible cells if these were re-added in the absence of selective antibiotics. Selection of resistant mutants was not observed with imipenem, despite the known tendency of this drug to select carbapenem-impermeable mutants ofP. aeruginosa in vivo. Imipenem, but not ceftazidime or meropenem, caused a significant post-antibiotic effect after single or repeated dosage.

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