title: In vitro time-kill curves of cefepime and cefpirome combined with amikacin, gentamicin or ciprofloxacin against Klebsiella pneumoniae producing extended-spectrum beta-lactamase.
abstract: Extended-spectrum beta-lactamases (ESBLs) are found in numerous Enterobacteriaceae, mainly in Klebsiella pneumoniae. We investigated the pharmacodynamics of two new extended-spectrum cephalosporins, cefepime and cefpirome, alone and combined with either amikacin or gentamicin or ciprofloxacin by means of time-kill curves against ESBL-producing, aminoglycoside-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 amikacin (4 mg/l) resulted in a 4 log decrease at 6 h, but there were no 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 combination of cefepime (32 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 cefpirome resulted in a 3 log decrease followed by regrowth at 24 h. The regrowth observed in the late phase with cefpirome alone disappeared when combined with aminoglycoside. When cefpirome (32 mg/l) was used in combination with ciprofloxacin (1 mg/l), it resulted in a 4 log decrease in 24 h.
authors.affiliation: Institut de Bactériologie, Strasbourg, France.
authors.forename: H
authors.initials: H
authors.lastname: Elkhaïli
authors.forename: N
authors.initials: N
authors.lastname: Kamili
authors.forename: L
authors.initials: L
authors.lastname: Linger
authors.forename: D
authors.initials: D
authors.lastname: Levêque
authors.forename: D
authors.initials: D
authors.lastname: Pompei
authors.forename: H
authors.initials: H
authors.lastname: Monteil
authors.forename: F
authors.initials: F
authors.lastname: Jehl
mesh_terms: D000583:Amikacin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000077723:Cefepime; D002511:Cephalosporins / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D005839:Gentamicins / Q000494:pharmacology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D013997:Time Factors; D001618:beta-Lactamases / Q000096:biosynthesis*; D000097572:Cefpirome
chemical_list: D000583:Amikacin; D000900:Anti-Bacterial Agents; D000077723:Cefepime; D002511:Cephalosporins; D002939:Ciprofloxacin; D005839:Gentamicins; D001618:beta-Lactamases; D000097572:Cefpirome