[Kinetics of bactericidal activity of cefepime and cefpirome alone or combined with gentamicin, amikacin or ciprofloxacin against Acinetobacter baumannii, Stenotrophomonas maltophilia and Enterobacter cloacae hyperproductive in cephalosporinase].

Nosocomial infections encountered in intensive care units are frequently due to Gram negative bacilli among which Stenotrophomonas maltophilia, Acinetobacter sp., and Enterobacter sp. The aim of the present study was to evaluate the in vitro bactericidal activity of the new broad spectrum cephalosporins cefepime (FEP) and cefpirome (CPO) alone or in combination with amikacin (AKN), gentamicin (GTN) or ciprofloxacin (CIP) against Acinetobacter baumannii, Stenotrophomonas maltophilia and Enterobacter cloacae producing a derepressed cephalosporinase. This study was performed by using the time-kill curve method on 24 h with a starting inoculum of 10(6) - 10(7) cfu/ml. The combination of FEP (4 mg/l) with AKN (4 mg/l) against A. baumanii only results in about 1 log decrease at 24 h, but when FEP is combined at 8 mg/l, the decrease reaches 4 log in 24 h. The combination of FEP (16 and 32 mg/l) clavulanic acid (4 mg/l) resulted in 3 log decrease at 24 h. When combined with CIP 2 mg/l, FEP (16 and 32 mg) resulted in 5 and 6 log decrease in 24 h respectively. There were no survival bacteria at 6 h when FEP (32 mg/l) was combined with clavulanic acid (4 mg/l) and GTN (8 mg/l) at 6 h. Used alone FEP (1 mg/l) or CPO (1 mg/l) against E. cloacae, a 3 log decrease occurs at 6 h followed by a regrowth at 24 h. Combined with AKN (2 mg/l), FEP (1 mg/l) results in a 6 log decrease at 24 h, when CPO at 2 mg/l is needed for an equivalent result. These data show synergistic bactericidal activity of both new extended cephalosporins combined with AKN, GTN or CIP at concentrations achievable in biological fluid with adaptative dosage regimen.