In vitro activity and post-antibiotic effects of linezolid in combination with fosfomycin against clinical isolates of <em>Staphylococcus aureus</em>

Abstract

ObjectivesLinezolid combination therapy is recommended for the treatment of Staphylococcus aureus (S. aureus) infections. However, the optimal regimen of the combination therapy for S. aureus is unknown. The objective of this study was to investigate the antibacterial activity, post-antibiotic effect (PAE), and post-antibiotic subminimum inhibitory concentration (MIC) effect (PA-SME) of linezolid alone and in combination with fosfomycin against eleven clinical isolates of S. aureus.MethodsThe synergistic effects and antibacterial activity of linezolid and fosfomycin were assessed by checkerboard and time-kill assays. To determine the PAE and PA-SME, S. aureus strains in the logarithmic phase of growth were exposed for 1, 2, and 3 hours to the antibiotics, alone and in combination. Recovery periods of test strains were evaluated using viable counting after dilution.ResultsSynergistic effects were observed for eight strains and no antagonism was found with any combination. Moreover, linezolid combined with fosfomycin at 4x MIC showed the best synergistic antibacterial effect, and this effect was retained after 24 hours. In addition, both the antibiotics alone and in combination showed increased PAE and PA-SME values in a concentration- and time-dependent manner.ConclusionLinezolid combined with fosfomycin exerted a good antibacterial effect against S. aureus, and the combinations have significant PAE and PA-SME.

Parenteral Fosfomycin for the Treatment of Multidrug Resistant Bacterial Infections: The Rise of the Epoxide

“…However, the PAE period is significantly shorter against S. aureus and ranges between 0.5 and 1.4 hours . This property potentially contributes to the ability of dosing fosfomycin less frequently and also combining it with other antibiotics known to have PAE properties (e.g., linezolid) …”

“…Fosfomycin combinations have also been evaluated against S. aureus . Cefazolin, doripenem, meropenem, moxifloxacin, and quinupristin/dalfopristin all demonstrated synergy in vitro against both methicillin‐susceptible S. aureus (MSSA) and MRSA .…”

“…Cefazolin, doripenem, meropenem, moxifloxacin, and quinupristin/dalfopristin all demonstrated synergy in vitro against both methicillin‐susceptible S. aureus (MSSA) and MRSA . Linezolid in combination with fosfomycin has also repeatedly demonstrated synergy against MSSA and MRSA in both in vitro testing and Galleria mellonella models . In contrast to other antibiotics tested in combination with fosfomycin, vancomycin in combination has demonstrated to be indifferent to antagonistic against S. aureus .…”

“…58,71 Fosfomycin combinations have also been evaluated against S. aureus. 67,70,[73][74][75] Cefazolin, doripenem, meropenem, moxifloxacin, and quinupristin/dalfopristin all demonstrated synergy in vitro against both methicillin-susceptible S. aureus (MSSA) and MRSA. 73,76 Linezolid in combination with fosfomycin has also repeatedly demonstrated synergy against MSSA and MRSA in both in vitro testing and Galleria mellonella models.…”

“…73,76 Linezolid in combination with fosfomycin has also repeatedly demonstrated synergy against MSSA and MRSA in both in vitro testing and Galleria mellonella models. 67,[73][74][75] In contrast to other antibiotics tested in combination with fosfomycin, vancomycin in combination has demonstrated to be indifferent to antagonistic against S. aureus. 73 Similar to Enterococcus species, rifampin plus fosfomycin demonstrated synergy against MRSA in vitro, and tigecycline demonstrated synergy as well, although against fewer isolates.…”