An in vitro study on combination effect of isepamicin and beta-lactam antibiotics

A study was done on the combined actions of an aminoglycoside, isepamicin (ISP), and 3 beta-lactam antibiotics (cefoperazone (CPZ), latamoxef (LMOX) and imipenem/cilastatin sodium (IPM/CS] against clinical isolates of Pseudomonas aeruginosa, Serratia marcescens and Klebsiella pneumoniae. Minimal inhibitory concentrations of individual antibiotics were compared first. ISP and IPM/CS had strong antibacterial activities against all 3 bacterial species while the antibacterial activities of CPZ against P. aeruginosa and S. marcescens, and that of LMOX against P. aeruginosa were much weaker than those of IPM/CS or ISP. Fractional inhibitory concentration indices determined by the checker-board dilution method were compared next. ISP, when used in combination with beta-lactam antibiotics (CPZ, LMOX, or IPM/CS), showed synergistic or additive effect on most strains of the all 3 species, the combination of ISP and CPZ being most effective. Although less effective, synergistic or additive effects were also observed with the combinations of 2 beta-lactam antibiotics (CPZ and IPM/CS, LMOX and IPM/CS). Time course experiments demonstrated that ISP combined with CPZ had bactericidal activities against all 3 bacterial species at concentrations at which the respective drug alone showed only bacteriostatic activity.