IN-VITRO TIME-KILL CURVES OF CEFEPIME AND CEFPIROME COMBINED WITH AMIKACIN, GENTAMICIN OR CIPROFLOXACIN AGAINST KLEBSIELLA-PNEUMONIAE PRODUCING EXTENDED-SPECTRUM BETA-LACTAMASE

Extended-spectrum beta-lactamases (ESBLs) are found in numerous Entero bacteriaceae, mainly in Klebsiella pneumoniae. We investigated the pha rmacodynamics of two new extended-spectrum cephalosporins, cefepime an d cefpirome, alone and combined with either amikacin or gentamicin or ciprofloxacin by means of time-kill curves against ESBL-producing, ami noglycoside-resistant K. pneumoniae. When used alone, cefepime (8 and 16 mg/l) resulted in a 2 and 3 log decrease at 6 h, respectively, but at 24 h regrowth occurred. The combination of cefepime (8 mg/l) with a mikacin (4 mg/l) resulted in a 4 log decrease at 6 h, but there were n o surviving bacteria at 6 h when combined with amikacin (8 mg/l). The combination of cefepime(16 mg/l) with gentamicin (4 mg/l) resulted in a 4 log decrease in 24 h. The antimicrobial combiantion of cefepime (3 2 mg/l) with ciprofloxacin (2 mg/l) resulted in a 4 log decrease in 24 h. Cefpirome (8 mg/l) induced a 2 log decrease at 4 h; 32 mg/l cefpir ome resulted in a 3 log decrease followed by regrowth al 24 h. The reg rowth observed in the late phase with cefpirome alone disappeared when combined with aminoglycoside. When cefpirome (32 mg/l) was used in co mbination with ciprofloxacin(1 mg/l), it resulted in a 4 log decrease in 24 h.