Abstract
BackgroundDaptomycin is an important drug used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. A high dose of daptomycin is indicated for an MRSA infection with a minimum inhibitory concentration (MIC) of 1 mg/L for daptomycin. Combination therapies with daptomycin and other antimicrobial agents, including fosfomycin, display in vitro synergism potentially. This study was conducted to investigate the in vitro synergistic effect of daptomycin-based combination therapy against MRSA strains with high daptomycin MIC.MethodThe synergistic effects of daptomycin in combination with fosfomycin, gentamicin, linezolid, oxacillin, or rifampicin against MRSA with an MIC of 1 mg/L for daptomycin were measured using the microbroth checkerboard assay in vitro.ResultA total of 100 MRSA isolates was tested. The synergistic interactions of the drugs were evaluated using the fractional inhibitory concentration index. The MIC values revealed that all isolates (100%) were found to be susceptible to linezolid, 85% to fosfomycin, 8% to gentamicin, 69% to rifampicin, and no isolate was susceptible to oxacillin. The in vitro synergism rates of daptomycin in combination with fosfomycin, oxacillin, gentamicin, linezolid, and rifampicin were 37, 11, 5, 3, and 1%, respectively.ConclusionThe combination of daptomycin plus fosfomycin may be an effective therapeutic option for MRSA infection.
Highlights
Daptomycin is an important drug used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection
The minimum inhibitory concentration (MIC) ranges, MIC50s, MIC90s, and the susceptible rates of the tested antimicrobials for the MRSA strains are listed in Table 1 and the detailed MICs are shown in Additional file 1
All strains (100%) were susceptible to linezolid, 85% to fosfomycin, 8% to gentamicin, 69% to rifampicin, and no strain was susceptible to oxacillin
Summary
Daptomycin is an important drug used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. Combination therapies with daptomycin and other antimicrobial agents, including fosfomycin, display in vitro synergism potentially. This study was conducted to investigate the in vitro synergistic effect of daptomycin-based combination therapy against MRSA strains with high daptomycin MIC. For the past few decades, methicillin-resistant Staphylococcus aureus (MRSA) continued to be a major human pathogen causing various dangerous infections, such as bacteremia, endocarditis, and abscess, in both community and hospital (nosocomial infection, health-care associated infection or hospital associated infection) settings [1]. Daptomycin was considered at least as effective as vancomycin in treating MRSA bacteremia, and high-dose daptomycin in combination with another agent, including gentamicin, rifampicin, linezolid, was suggested to be the option against persistent MRSA bacteremia with vancomycin treatment failures [5].
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