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[An in vitro study on combination effect of isepamicin and beta-lactam antibiotics]
K Kumagai1, H Otsuki, M Nishibuchi
1Department of Microbiology, School of Medicine, Kyoto University.
Abstract:
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.
Insights
The combination of isepamicin (ISP) with beta-lactam antibiotics like cefoperazone (CPZ) demonstrated synergistic effects against Pseudomonas aeruginosa, Serratia marcescens, and Klebsiella pneumoniae. This combination showed potent bactericidal activity, enhancing treatment options.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Antibiotic resistance is a growing threat in treating Gram-negative bacterial infections.
- Aminoglycosides and beta-lactams are crucial antibiotic classes, but their combined efficacy requires investigation.
- Pseudomonas aeruginosa, Serratia marcescens, and Klebsiella pneumoniae are significant opportunistic pathogens.
Purpose of the Study:
- To evaluate the synergistic, additive, or antagonistic effects of isepamicin (ISP) combined with beta-lactam antibiotics.
- To assess the antibacterial activity of these combinations against clinical isolates of P. aeruginosa, S. marcescens, and K. pneumoniae.
- To determine the bactericidal potential of effective combinations.
Main Methods:
- Minimal Inhibitory Concentration (MIC) determination for individual antibiotics.
- Checkerboard dilution method to calculate Fractional Inhibitory Concentration (FIC) indices.
- Time-course experiments to assess bactericidal activity.
Main Results:
- Isepamicin (ISP) and imipenem/cilastatin sodium (IPM/CS) exhibited strong activity against all tested species.
- Combinations of ISP with beta-lactams (cefoperazone (CPZ), latamoxef (LMOX), IPM/CS) showed synergistic or additive effects on most strains.
- The ISP-CPZ combination was particularly effective, demonstrating bactericidal activity where individual drugs were only bacteriostatic.
Conclusions:
- Combined therapy of isepamicin with beta-lactam antibiotics offers synergistic or additive benefits against key Gram-negative pathogens.
- The combination of isepamicin and cefoperazone shows significant potential for bactericidal activity, improving treatment outcomes.
- These findings support the clinical utility of antibiotic combinations in combating challenging bacterial infections.