In vitro activity of vancomycin combined with rifampin, amikacin, ciprofloxacin or imipenem against methicillin-resistant and methicillin-susceptible Staphylococcus aureus

Abstract

I n spite of great advances in the antimicrobial chemotherapy era, staphylococci are still the most important nosocomial pathogens in many countries. The methicihn-resistant strains are often resistant not only to p-lactam agents but also to chloramphenicol, clindamycin, tetracyclines and aminoglycosides. Vancomycin and teicoplanin are the drugs of choice for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Since the relationship between plasma levels of teicoplanin and clinical outcome is not well established, vancomycin remains the preferred agent. Various in vitro antibiotic combinations have been tested in attempis to find a better treatment regimen for staphylococcal infections [1-4]. Because vancomycin is the drug generally available for multiresistant staphylococcal species, the synergistic activities of vancomycin with rifampin, amikacin, ciprofloxacin or imipenem were tested. Five MRSA and five methicillin-sensitive Staphylococcus aureus (MSSA) strains isolated from blood, pus and catheters of patients hospitalized in different intensive care units of the same hospital were used in the study, and S. aureus ATCC 29213 was used as the control strain. The antibiotics were kindly provided by the manufacturers: vancomycin (Lilly, USA), amikacin (EczacibaSi, Turkey), rifampin (Sifar, Turkey), ciprofloxacin (Bayer, Turkey) and imipenem (MSD, USA). Methicillin-resistant strains were identified by the disk diffusion method with a 1-pg oxacillin disk. The minimum inhibitory concentrations (MICs) were determined by the broth microdilution method as described by the NCCLS [5]. According to MIC values of the antibiotics, checkerboard microdilution panels were prepared and fractional inhibitory concentrations (FICs) of vancomycin-rifampin, vancomycin-amikacin, vancomycin-ciprofloxacin and vancomycin-imipenem were determined as described elsewhere [6]. Fractional inhibitory concentration indices (FICIs) were determined for each combination. FICIs0.5 was defined as synergy, 0.5 4 as antagonism [6]. The MIC ranges of the antibiotics tested are given in Table 1. The mean FICls of the antibiotic combinations are given in Table 2. Vancomycin-amikacin was synergistic for all MSSA strains and one MRSA strain. Vancomycin-rifampin was indifferent against the S. aureus strains tested, either methicilhn sensitive or