Bactericidal effect of β-lactams and amikacin alone or in association against Klebsiella pneumoniae producing extended spectrum β-lactamase

Abstract

Ten extended spectrum β-lactamases producing strains of Klebsiella pneumoniae characterized by analytical isoelectric focusing and studied for their susceptibility to /Mactam antibiotics, either alone or in combination with a β-lactamase inhibitor (clavulanic acid and sulbactam) and in association with amikacin. The extended spectrum β-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 × 4. At MIC, cefotetan, cefotaxime and ceftazidime lacked bactericidal activity. Imipenem was more rapidly bactericidal than meropenem or co-amoxiclav. At MIC × 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 arapid 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 βMactamase associated K. pneumoniae injections.