Novobiocin and rifampicin in combination against methicillin-resistant Staphylococcus aureus: an in-vitro comparison with vancomycin plus rifampicin.

Novobiocin and rifampicin were evaluated in vitro as a possible new antibiotic combination against methicillin-resistant Staphylococcus aureus. An evaluation of 20 strains of methicillin-resistant Staph. aureus using microdilution checkerboard techniques at 10(5) cfu/ml showed neither synergy nor antagonism between novobiocin and rifampicin or between vancomycin and rifampicin. Agar surface inoculation of six strains of methicillin-resistant Staph. aureus showed increased synergy with increased inocula (10(6)-10(9) cfu) for novobiocin plus rifampicin compared to vancomycin plus rifampicin. Time-kill curves showed indifference at 6h for all combinations, whereas, at 24 and 48 h, they generally showed indifference, occasionally synergy, but never antagonism. The 'synergy' between novobiocin and rifampicin at higher inocula of methicillin-resistant Staph. aureus appears to be due to prevention of emergence of resistant organisms and may have clinical relevance. The combination of novobiocin-rifampicin merits further investigation.