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

Yi-Chien Lee,
Pao-Yu Chen,
Jann-Tay WangEmail author and
Shan-Chwen Chang

BMC Pharmacology and Toxicology201920:25

https://doi.org/10.1186/s40360-019-0305-y

Received: 26 December 2018
Accepted: 23 April 2019
Published: 6 May 2019

Open Peer Review reports

Abstract

Background

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.

Method

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.

Result

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.