Response of chemostat cultures of Pseudomonas aeruginosa to carbapenems and other /Mactams

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 /Mactamase expression were selected when a /Mactamase inducible (i.e. typical) strain was challenged with ceftazidime or piperacillin. Addition of the /Mactamase 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 carba-penem-impermeable mutants of P. aeruginosa in vivo. Imipenem, but not ceftazidime or meropenem, caused a significant post-antibiotic effect after single or repeated dosage