Objectives: The efficacies of antimicrobial agents in the treatment of infections depends upon the interactions of bacteria, antibiotic and phagocytes. The aim of this study was to determine whether liposome-encapsulation of vancomycin and ofloxacin, when compared with their free forms, can enhance the drug activity at the same concentrations against S. aureus strains located within human macrophages. Methods: Methicillin-resistant S. aureus (MRSA) (ATCC 43300) and methicillin-sensitive S. aureus (MSSA) (ATCC 29213) strains were used in these studies. Vancomycin (VAN) (Lilly USA), ofloxacin (OFX) (Hoechst M.R-Germany) and two forms which were made up of distearyl phosphatidyl choline (DPPC)-dicetyl phosphate (DCP)-cholesterol (CHOL) and phospholipon 90G (PL 90G)-(DCP)-(CHOL) (10:1:4 molar ratio) of liposomal-vancomycin (L-VAN) and liposomal-ofloxacin (L-OFX) were tested at different minimum inhibitory concentrations (MICs). The MICs of VAN and OFX were determined against S. aureus strains by the microdilution method in cation-supplemented Mueller Hinton broth. The extracellular and intracellular bactericidal activities of antimicrobial agents were investigated at the 4 MIC, 2 MIC, 1 MIC, 1/2 MIC, 1/4 MIC, and 1/8 MIC values at 0, 3, 6 and 12 h time following inoculation. The liposomal forms were used at equal MICs with free drugs. The cultures of human macrophages were used for this aim. Results: The MICs of VAN and OFX were 0.250 mg/mL for MSSA. For MRSA, the MICs of VAN and OFX were 1.000 mg/mL and 0.500 mg/mL, respectively. The effects of liposomal forms were not observed in the medium without cells. The bactericidal activities of free drug were more effective at the tested concentrations against MSSA. The reduction in intracellular efficacy of VAN wasobserved afterthe sixthhour.When L-VANand L-OFXwereloweffective at4MIC,They were ineffective at other concentrations.
Full conference title:
11th European Congress of Clinical Microbiology and Infectious Diseases
- ECCMID 11th (2001)