title: In vitro efficacy of fosfomycin-based combinations against clinical vancomycin-resistant Enterococcus isolates.
abstract: Vancomycin-resistant (VR) enterococci (VRE) are increasingly important nosocomial pathogens, commonly causing catheter-related urinary tract infections or vascular catheter-related bloodstream infections. In this study, 10 Enterococcus faecium and 9 Enterococcus faecalis different pulsed-field gel electrophoresis genome-type VR clinical isolates were detected. The potential role of fosfomycin-based combination regimens for biofilm-related VRE infection is in vitro evaluated. Anti-VRE activities of fosfomycin, ampicillin, linezolid, minocycline, rifampicin, tigecycline, teicoplanin, vancomycin alone, or fosfomycin-based combinations were studied by time-kill method and a biofilm model. Of the fosfomycin-based combinations, a synergistic effect was particularly noted for teicoplanin against 89% of the VR E. faecalis isolates. In a biofilm model, only linezolid alone was able to reduce the bacterial loads, and the use of fosfomycin-based combinations, excluding rifampicin (40%), failed to enhance antibacterial activity against VR E. faecium. For E. faecalis, an inhibitory effect was evident using ampicillin alone or fosfomycin plus rifampicin (100%), tigecycline (56%), or teicoplanin (44%). However, an antagonistic effect was found for ampicillin plus fosfomycin against 2 of 3 of the VR E. faecalis isolates. The antibacterial activities of the drugs tested against VRE in vitro varied by species. Ampicillin exhibited potential activity against planktonic- and biofilm-embedded VR E. faecalis. Fosfomycin-based combinations may have enhanced antibacterial effects against VRE even in the biofilm model, and this observation warrants further clinical studies.
authors.affiliation: Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Tang
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Chen
authors.forename: Chun-Cheng
authors.initials: CC
authors.lastname: Zhang
authors.forename: Bo-An
authors.initials: BA
authors.lastname: Su
authors.forename: Chien-Ming
authors.initials: CM
authors.lastname: Li
authors.forename: Tzu-Chieh
authors.initials: TC
authors.lastname: Weng
authors.forename: Shyh-Ren
authors.initials: SR
authors.lastname: Chiang
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Ko
authors.forename: Yin-Ching
authors.initials: YC
authors.lastname: Chuang
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004357:Drug Synergism; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000302:isolation & purification; D016984:Enterococcus faecium / Q000187:drug effects* / Q000302:isolation & purification; D005578:Fosfomycin / Q000494:pharmacology*; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin
keywords: Biofilm; Synergistic effect; Vancomycin-resistant enterococci