title: Efficacy of combined vancomycin and fosfomycin against methicillin-resistant Staphylococcus aureus in biofilms in vivo.
abstract: Infection by methicillin-resistant Staphylococcus aureus (MRSA) is a life-threatening condition, and formation of biofilms can lead to treatment failure in a clinical setting. The aim of this study was to demonstrate the in vivo bactericidal effects of a combination of vancomycin (VAN) and fosfomycin (FOS) against MRSA in a rat carboxymethyl cellulose-pouch biofilm model. The results of the time-kill assay showed that the combination therapy was capable of killing at low minimal inhibitory concentrations (MIC) (½ × MIC VAN +1 × MIC FOS and 1 × MIC VAN + 1 × MIC FOS). In the in vivo study, a synergistically bactericidal effect was observed when using the combination therapy on MRSA embedded in the mature biofilm model. In comparison with the untreated control group and the groups receiving either VAN or FOS alone, the rats treated with combination therapy had lower MRSA colony counts in exudates from the pouch, lower white blood cell and neutrophil counts, and C-reactive protein (CRP) in peripheral blood. Furthermore, histological analysis of the pouch wall indicated combination therapy resulted in disappearance of biofilm-like structures, marked decrease in necrosis, and formation of granular tissue. In conclusion, the combination of VAN with FOS had a synergistic bactericidal effect on chronic MRSA infection embedded in biofilm, providing an alternative approach to treating this condition.
authors.affiliation: Department of Orthopedics, Kunming General Hospital of Chengdu Military Region, Kunming, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Orthopedics, Changhai Hospital, Shanghai, China.
authors.forename: Ning-Fang
authors.initials: NF
authors.lastname: Mao
authors.affiliation: Department of Pathology, Kunming General Hospital of Chengdu Military Region, Kunming, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Laboratory of Conservation and Utilization for Bio-resources and Key Laboratory for Microbial Resources of the Ministry of Education, Yunnan University, Kunming, China.
authors.forename: Han-Bo
authors.initials: HB
authors.lastname: Zhang
authors.affiliation: Department of Infection Control, Kunming General Hospital of Chengdu Military Region, Kunming, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Kunming General Hospital of Chengdu Military Region, Kunming, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Kunming General Hospital of Chengdu Military Region, Kunming, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Orthopedics, Kunming General Hospital of Chengdu Military Region, Kunming, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
authors.affiliation: Department of Orthopedics, Kunming General Hospital of Chengdu Military Region, Kunming, China.
authors.forename: Chong-Tao
authors.initials: CT
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics, Kunming General Hospital of Chengdu Military Region, Kunming, China.
authors.forename: Fu-Bing
authors.initials: FB
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Kunming General Hospital of Chengdu Military Region, Kunming, China.
authors.forename: Lin-Hui
authors.initials: LH
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, Kunming General Hospital of Chengdu Military Region, Kunming, China.
authors.forename: Xin-Ming
authors.initials: XM
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Kunming General Hospital of Chengdu Military Region, Kunming, China.
authors.forename: Yong-Qing
authors.initials: YQ
authors.lastname: Xu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018441:Biofilms / Q000187:drug effects*; D002097:C-Reactive Protein / Q000378:metabolism; D004357:Drug Synergism; D005578:Fosfomycin / Q000494:pharmacology* / Q000627:therapeutic use; D007958:Leukocyte Count; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology*; D008826:Microbial Sensitivity Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000097:blood / Q000188:drug therapy; D014640:Vancomycin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin; D014640:Vancomycin; D002097:C-Reactive Protein