Vancomycin-Gentamicin Synergism against Methicillin-resistant Staphylococcus aureus : Relationship with Gentamicin Susceptibility

Kim, Eun Ok; Kim, Yang Soo; Kim, Baek Nam; Park, Su Jin; Lee, Sang Oh; Chung, Doo Ryeon; Kim, Mi Na; Woo, Jun Hee; Pay, Chik Hyun; Ryu, Ji So

Abstract

BACKGROUND
Vancomycin is the drug of choice for the treatment of infections caused by methicillin- resistant Staphylococcus aureus(MRSA). However, vancomycin monotherapy of deep-seated staphylococcal infection may be associated with poor bacteriological response. Limited data suggest that vancomycin- gentamicin combination therapy is effective against MRSA. In this study, we evaluated the vancomycin- gentamicin synergism against MRSA and also investigated whether gentamicin susceptibility may affect the synergism.
MATERIALS AND METHODS
The 51 strains of MRSA were obtained from patients at the Asan Medical Center from 1995 to 1996. The minimal inhibitory concentrations(MICs) of gentamicin were determined by the agar dilution method. The 25 strains with various levels of gentamicin MICs were chosen for time-kill studies. The MICs and minimal bactericidal concentrations(MBCs) of vancomycin were defined to determine vancomycin tolerance. Time-kill curves were established with vancomycin, gentamicin, and a combination of both.
RESULTS
Gentamicin MICs ranged from 4 to 512microgram/mL. Only 7 of the 51 strains were gentamicin-susceptible and 44 were resistant. All of the 25 strains chosen were susceptible to vancomycin, but 16 of them showed tolerance. Vancomycin-gentamicin synergism was demonstrated in 5 of the 18 strains, in which the analysis of drug interaction was possible. In the remaining 13 strains, vancomycin and gentamicin interacted in a nonsynergistic manner. In all strains that showed synergism, the MICs of gentamicin were below 32microgram/mL. No synergism was demonstrated in strains with gentamicin MICs above 64microgram/mL.
CONCLUSIONS
Although most of MRSA strains are resistant to gentamicin, synergistic interaction between vancomycin and gentamicin may be expected when the MIC of gentamicin is below 32 microgram/mL.