Development of resistance and cross-resistance in Pseudomonas aeruginosa exposed to subinhibitory antibiotic concentrations

The purpose of this study was to compare resistance and cross-resistance de velopment in Pseudomonas aeruginosa isolates from cystic fibrosis (CF) pati ents to commonly used antipseudomonal antibiotics. Isolates were repeatedly exposed to subinhibitory concentrations of either azlocillin, tobramycin, ceftazidime or ciprofloxacin. On 10 consecutive occasions, samples were rem oved from the half-MIG well of a microtitre plate and regrown in drug-free medium to provide the next inoculum for MIC determination. The increase in MIC at the end of the treatment period was significant (p<0.05) for all sel ecting antibiotics. Cross-resistance to unrelated antibiotics was not obser ved, but was significant (p<0.05) in all p-lactams (ticarcillin, piperacill in, ceftazidime and cefsulodin) studied where azlocillin was the selecting antibiotic. The addition of clavulanic acid to ticarcillin and of tazobacta m to piperacillin had no effect on cross-resistance. The development of res istance to azlocillin was associated with increased p-lactamase activity an d a change in isoelectric point of the B-lactamases. The result of this stu dy supports a rotational policy for antipseudomonal antibiotics in CF patie nts.