Abstract
BackgroundFosfomycin 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.MethodsAll 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.ResultsA 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.ConclusionsAn 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.
Highlights
Fosfomycin exhibits excellent in vitro activity against multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA)
Most of the previous studies investigated the mechanism of fosfomycin resistance among Gram-negative bacteria, and only limited information about the resistance mechanism of Grampositive pathogens, MRSA, is available
Elderly patients seemingly had the tendency of acquisition of fofsomycin-resistant MRSA infections, and the vast majority of those resistant strains were isolated from those hospitals located in central or southern Taiwan
Summary
Fosfomycin exhibits excellent in vitro activity against multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Numerous studies have demonstrated the excellent in vitro susceptibility of multidrug-resistant and extensively drug-resistant organisms (MDRO and XDROs) to fosfomycin, including vancomycin-resistant enterococci (VRE) (96%) [3], ESBL-producing Enterobacteriaceae (87.7%) [4], carbapenem-resistant Gram-negative bacteria (99%) [5], and methicillin-resistant Staphylococcus aureus (MRSA) (99.6%) [6]. The synergistic effect of fosfomycin in combination with other relevant antibiotics against the above-mentioned MDR microorganisms, evaluated by time-kill experiments, checkerboard analysis and E-test methods [7,8,9], was promising These studies indicated that fosfomycin could be a potential treatment option for the difficult-to-treat infections caused by drug-resistant organisms. In the present study, we aimed to survey the prevalence of fosfomycin resistance and the associated uhpT, glpT, murA, and fosB genetics in clinical isolates of MRSA in Taiwan
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