Dataset Information

In vitro activity and post-antibiotic effects of linezolid in combination with fosfomycin against clinical isolates of Staphylococcus aureus.

ABSTRACT:

Objectives

Linezolid 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.

Methods

The 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.

Results

Synergistic 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.

Conclusion

Linezolid combined with fosfomycin exerted a good antibacterial effect against S. aureus, and the combinations have significant PAE and PA-SME.

SUBMITTER: Chen H

PROVIDER: S-EPMC6219420 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

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

Chen Hao H Li Lan L Liu Yanyan Y Wu Maomao M Xu Shuangli S Zhang Guijun G Qi Caifen C Du Yan Y Wang Mingli M Li Jiabin J Huang Xiaohui X

Infection and drug resistance 20181101

<h4>Objectives</h4>Linezolid combination therapy is recommended for the treatment of <i>Staphylococcus aureus</i> (<i>S. aureus</i>) infections. However, the optimal regimen of the combination therapy for <i>S. aureus</i> 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 isola ...[more]

PMID: 30464553

Similar Datasets

Project description:BACKGROUND:Fosfomycin exhibits excellent in vitro activity against multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Increasing fosfomycin resistance among clinical MRSA isolates was reported previously, but little is known about the relative abundance of Fosfomycin resistance genes in MRSA isolates circulating in Taiwan. METHODS:All MRSA isolates, collected in 2002 and 2012 by the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program, were used in this study. Susceptibility to various antimicrobial agents, including fosfomycin, was determined by broth microdilution. Genetic determinants of fosfomycin resistance, including fosB carriage and murA, glpT and uhpT mutations, were investigated using PCR and sequencing of amplicons. Staphylococcal protein A (spa) typing was also performed to determine the genetic relatedness of MRSA isolates. RESULTS:A total of 969 MRSA strains, 495 in the year 2002 and 474 in the year 2012, were analyzed. The overall in vitro susceptibility was 8.2% to erythromycin, 18.0% to clindamycin, 29.0% to tetracycline, 44.6% to ciprofloxacin, 57.5% to trimethoprim/sulfamethoxazole, 86.9% to rifampicin, 92.9% to fosfomycin and 100% to linezolid and vancomycin. A significant increase in the fosfomycin resistance rate was observed from 3.4% in 2002 to 11.0% in 2012. Of 68 fosfomycin-resistant MRSA isolates, several genetic backgrounds probably contributing to fosfomycin resistance were identified. Twelve isolates harbored the fosB gene, and various mutations in murA, uhpT, and glpT genes were noted in 11, 59, and 66 isolates, respectively. The most prevalent gene mutations were found in the combination of uhpT and glpT genes (58 isolates). The vast majority of the fosfomycin-resistant MRSA isolates belonged to spa type t002. CONCLUSIONS:An increased fosfomycin resistance rate of MRSA isolates was observed in our present study, mostly due to mutations in the glpT and uhpT genes. Clonal spread probably contributed to the increased fosfomycin resistance.