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

Cultures of Pseudomonas aeruginosa were grown at different rates in a chemostat and challenged continuously or intermittently with ceftazidime, imipenem, meropenem 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 beta-lactamase expression were selected when a beta-lactamase inducible (i.e. typical) strain was challenged with ceftazidime or piperacillin. Addition of the beta-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 readded 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 of P. aeruginosa in vivo. Imipenem, but not ceftazidime or meropenem, caused a significant post-antibiotic effect after single or repeated dosage.