BACTERICIDAL ACTIVITY OF CEFPIROME-AMINOG LYCOSIDE COMBINATIONS AGAINST PSEUDOMONAS-AERUGINOSA STRAINS SHOWING INTERMEDIATE SUSCEPTIBILITY TO CEFPIROME AND VARIOUS BETA-LACTAM RESISTANCE MECHANISMS

The bactericidal activity of cefpirome (CPO)-aminoglycoside (AG) combi nation was assessed by a kinetic time-kill method against 8 strains of Pseudomonas aeruginosa showing intermediate susceptibility to cefpiro me (MICS: 8-32 mg/l), Six strains had an acquired beta-lactam resistan ce mechanism (moderate cephalosporinase hyperproduction, OXA-2 or PSE- 1 enzyme production, non enzymatic resistance) and one strain was resi stant to tobramycin (TOE). Antibiotic concentrations used for time-kil l curves were 1/2, 1 and 2 x MIC for cefpirome, 8 mg/l for tobramycin and 16 mg/l for amikacin (AKN). Bactericidal activity was defined as a (4 log(10) reduction of the initial inoculum. At the concentrations u sed in this study, CPO was not bactericidal; AG were bactericidal in 3 to 24 hours, CPO-AG combination was bactericidal against all the stra ins with no secondary regrowth. For 7/8 strains, the combination of CP O with TOB and/or AKN was more rapidly bactericidal than the AG alone. In conclusion, despite an intermediate susceptibility against numerou s strains of P. aeruginosa, the CPO-AG combination is bactericidal at concentrations achievable with standard dosing regimens in man.