Escherichia coli resistant to β-lactam antibiotics : A study of bactericidal activity of penicillins in combination with β-lactamase inhibitors

摘要

Objectives. — The increasing implication of resistant Escherichia coli in severe infections required updating of bactericidal power of β-lactams used alone or in antibiotic combinations. Methods. — Four clinical E. coli isolates have been selected, having different resistance mechanisms to β-lactams. Bactericidal effect of amoxicillin, piperacillin and ticarcillin have been tested by means of bactericidal kinetics, with concentrations 2 x MIC and combinations with β-lactamase inhibitors and gentamicin (at its MICs 1 or 2 mg/L). A pharmacodynamic approach used in vitro for bactericidal kinetics residual antibiotic concentrations as established previously for piperacillin, ticarcillin and their inhibitors in patients' serum collected during treatments including these antibiotics. Results. — In all bactericidal tests, the addition of gentamicin to penicillins (amoxicillin, piperacillin, ticarcillin) enforced bactericidal power of penicillins. Bactericidal effects of piperacillin and ticarcillin varied when tested with or without β-lactamase inhibitors against a penicillinase producer. Against a high-level cephalosporinase producer, high amoxicillin concentration (256 mg/L) resulted in a short bactericidal effect only in the presence of gentamicin. In contrast, piperacillin presented a persistent bactericidal activity in the presence of tazobactam and gentamicin 2 mg/L, but regrowth occurred with gentamicin 1 mg/L. Ticarcillin showed the most rapid and persistent (> 24 h) bactericidal effect when associated with clavulanic acid and gentamicin 2 mg/L. The tests carried out in simulation of in vivo conditions provided similar bactericidal effects as in vitro. Synergistic effects of combination of a β-lactam plus gentamicin is confirmed all along the study.