A study on combination of daptomycin with selected antimicrobial agents: in vitro synergistic effect of MIC value of 1 mg/L against MRSA strains

• Published in: BMC pharmacology & toxicology Vol. 20; no. 1; pp. 25 - 6
• Main Authors: Lee, Yi-Chien, Chen, Pao-Yu, Wang, Jann-Tay, Chang, Shan-Chwen
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06.05.2019; BioMed Central; BMC
• Subjects: Aminoglycosides; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics; Antiinfectives and antibacterials; Antimicrobial agents; Biofilms; Checkerboard assays; Combination therapy; Daptomycin; Daptomycin - pharmacology; Displays (Marketing); Drug development; Drug dosages; Drug interactions; Drug resistance; Drug Synergism; Drug therapy; Endocarditis; Fosfomycin; Fosfomycin - pharmacology; Gentamicin; Gentamicins - pharmacology; Health aspects; Infection; Infections; Laboratories; Linezolid; Linezolid - pharmacology; Methicillin; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - growth & development; Microbial Sensitivity Tests; Minimum inhibitory concentration; MRSA; Nosocomial infections; Oxacillin; Oxacillin - pharmacology; Prostheses; Rifampin; Rifampin - pharmacology; Staphylococcal infections; Staphylococcus aureus; Staphylococcus aureus infections; Staphylococcus infections; Studies; Synergism; Synergistic effect; Taiwan; United States > US; Checkerboard assays; Combination therapy; Daptomycin; MRSA
• ISSN: 2050-6511; 2050-6511
• DOI: 10.1186/s40360-019-0305-y

Daptomycin 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. The 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. A 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. The combination of daptomycin plus fosfomycin may be an effective therapeutic option for MRSA infection.