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

The 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.

The in vitro activity of LZD in combination with five different antibiotics was evaluated using a microdilution checkerboard method and time-kill study against 12 clinical enterococcus isolates.

With 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 combinations—LZD + DX and LZD + CRO—showed an indifferent interaction. One tested combination of LZD + rifampicin showed antagonism.

Antagonistic 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.