Evaluation of Cefixime-Clavulanate Combination by Comparative Disk Diffusion Method in Klebsiella Pneumoniae Clinical Isolates-An In-Vitro Study .

摘要

Background: Resistance to cephalosporins due to β-lactamases is a major concern worldwide. However recent trend is to use β-lactamase inhibitor combinations. Potential combination is cefixime-clavulanate. Objective: Present study aims at the comparative evaluation of Fixed-Dose Combination (FDC) of cefixime-clavulanate and cefixime-alone in Klebsiella pneumoniae clinical isolates. Material and Methods: Study included 200 clinical isolates of K. pneumoniae. The Comparative Antimicrobial Susceptibility Test (AST) of cefixime-clavulanate (5μg/10μg) combination and cefixime-alone(5μg)was done by measurement and comparison of zone of lysis produced by both. All values were expressed in mean ± SD. Paired't' test was used to determine statistical difference between different groups under study. P values < 0.05 were considered statistically significant. Isolates were tested for Extended-Spectrum β-lactamase (ESBL), AmpC β-lactamase (AmpC) and metallo β-lactamase (MBL) production by Clinical Laboratory Standards Institute - Phenotypic Disk Confirmatory Test (CLSI-PDCT), AmpC β-lactamase sterile disk test andImipenem-Ethylene Di-amine Tetracetic Acid – Double disk synergy test (Imipenem-EDTA DDST) respectively. Results: Comparative AST resulted in statistically significant (P < 0.001) increased zones in cefixime-clavulanate combination than cefixime-alone in all isolates studied. When zones were evaluated separately only in three β-lactamase producing isolates; cefixime-clavulanate combination showed much higher zones in ESBL-producers (n=30) (P < 0.001), but not in AmpC-producers (n=32) (P = 0.5559) and MBL-producers (n=06) (P = 0.7815). Conclusion: Present study demonstrates the best bactericidal killing effect of cefixime-clavulanate compared to cefixime-alone. It is also of therapeutic significance in the treatment of infections caused by K. pneumoniae producing ESBLs. We recommend comparative AST method when commercially available newer β-lactamase inhibitor combination, for which no CLSI interpretive guidelines are available; to be studied systematically, before implementing it in treatment regimen.