Bactericidal effect of beta-lactams and amikacin alone or in association against Klebsiella pneumoniae producing extended spectrum beta-lactamase.
Ten extended spectrum beta-lactamases producing strains of Klebsiella pneumoniae characterized by analytical isoelectric focusing and studied for their susceptibility to beta-lactam antibiotics, either alone or in combination with a beta-lactamase inhibitor (clavulanic acid and sulbactam) and in association with amikacin. The extended spectrum beta-lactamases were derived from either TEM (CTX-1 = TEM-3) or SHV (CAZ-4 = SHV-5). Killing curves were studied with antibiotics at clinical by achievable concentrations, at MIC and MIC x 4. At MIC, cefotetan, cefotaxime and ceftazidime lacked bactericidal activity. Imipenem was more rapidly bactericidal than meropenem or co-amoxiclav. At MIC x 4, cefotetan and cefotaxime exhibited bactericidal effect but this was less than for imipenem which gave a reduction of 4 log10 of the inoculum. Cefotaxime plus sulbactam gave no bactericidal effect compared with cefotaxime plus co-amoxiclav. A bactericidal effect with cefotaxime plus sulbactam was seen with the addition of amikacin. At clinical concentrations cefotaxime plus co-amoxiclav +/- amikacin was as efficient as imipenem +/- amikacin with a rapid bactericidal effect (5-6 log10 in 30-60 min). We proposed that cefotaxime+co-amoxiclav might be considered as an alternative to imipenem for the treatment of extended spectrum beta-lactamase associated K. pneumoniae injections.
Lab. Bactériologie-virologie-hygiène, Hôpital A. Calmette, Lille, France.
M
M
Roussel-Delvallez
D
D
Sirot
Y
Y
Berrouane
M
M
Goffart
B
B
Gourde
F
F
Wallet
R J
RJ
Courcol
D000583:Amikacin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D007525:Isoelectric Focusing; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology*; D008826:Microbial Sensitivity Tests; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000737:chemistry; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D000583:Amikacin; C117193:beta-lactamase SHV-5; C055184:beta-lactamase TEM-3; D001618:beta-Lactamases