Emergence of β-lactam resistance in Pseudomonas aeruginosa

Abstract

The emergence of β-lactam resistant mutants of Pseudomonas aeruginosa S-1278, a clinical isolat susceptible to β-lactams, was investigated in a rat pouch infection model using 4 β-lactam antibiotics: piperacillin (PIPC), tazobactam/piperacillin (TAZ/PIPC), ceftazidime (CAZ), and imipenem (IPM). After intravenous administration of 20 and 100mg/kg of each drug in the rat pouch infection model, the frequency of mutants resistant to PIPC and TAZ/PIPC were <1.0×10^-5 to 3.7×10^-8: lower than those of CAZ and IPM (2.4×10^-5 to 7.5×10^-5). The frequency of mutants resistant to CAZ increased drastically after 3 administrations, and its frequency (4.7×10^-2 to 2.17times;10^-1) was the highest. No significant difference of frequency of resistant mutants was seen among the 4 β-lactam antibiotics in vitro, but CAZ selected resistant mutants in a wider concentration than in other antibiotics. In conclusion, the frequency of mutants resistant to PIPC was comparable to that of TAZ/PIPC, and was lower than for CAZ and IPM in the rat pouch infection model.