In vitro activity of linezolid alone and combined with other antibiotics against clinical enterococcal isolates

BackgroundThe increasing incidence of antimicrobial resistance has led to research on finding new antimicrobial agents or identifying drug combinations with synergistic effects. Enterococcal infections, particularly those associated with vancomycin-resistant enterococci (VREs), are therapeutic problems. Linezolid (LZD), an oxazolidinone antibiotic, shows good activity against Gram-positive bacteria including enterococci. To avoid the emergence of linezolid-resistant subpopulations and achieve enhanced activity or bactericidal effect, the use of combined therapy has been considered.MethodsThe in vitro activity of LZD in combination with five different antibiotics was evaluated using amicrodilution checkerboard method and time-kill study against 12clinical enterococcus isolates.ResultsWith the checkerboard method, LZD plus doxycycline (DX) had the highest frequency among all synergistic combinations. This combination and the one of LZD plus ceftriaxone (CRO) were the most frequent effective combinations against VREs. Time-kill studies using selected synergistic combinationsLZD+ DX and LZD+ CROshowed anindifferent interaction. One tested combination of LZD+ rifampicin showed antagonism.ConclusionsAntagonistic interactions in combinations containing LZD are rare. LZD+ DX and LZD+ CRO may be beneficial in the treatment of VREs. However, more time-kill studies as well as in vivo experiments are required.