title: Efficacy of Linezolid and Fosfomycin in Catheter-Related Biofilm Infection Caused by Methicillin-Resistant Staphylococcus aureus.
abstract: As long-standing clinical problems, catheter-related infections and other chronic biofilm infections are more difficult to treat due to the high antibiotic resistance of biofilm. Therefore, new treatments are needed for more effective bacteria clearance. In this study, we evaluated the antibacterial activities of several common antibiotics alone and their combinations against biofilm-embedded methicillin-resistant staphylococcus aureus (MRSA) infections, both in vitro and in vivo. In brief, fosfomycin, levofloxacin, and rifampin alone or in combination with linezolid were tested in vitro against planktonic and biofilm-embedded MRSA infection in three MRSA stains. The synergistic effects between linezolid and the other three antibiotics were assessed by fractional inhibitory concentration index (FICI) and time-kill curves, where the combination of linezolid plus fosfomycin showed the best synergistic effect in all strains. For further evaluation in vivo, we applied the combination of linezolid and fosfomycin in a catheter-related biofilm rat model and found that viable bacteria counts in biofilm were significantly reduced after treatment (P < 0.05). In summary, we have shown here that the combination of linezolid and fosfomycin treatment had improved therapeutic effects on biofilm-embedded MRSA infection both in vitro and in vivo, which provided important basis for new clinical therapy development.
authors.affiliation: Department of Pharmaceutical Care, PLA General Hospital, 28 Fu Xing Road, Beijing 100853, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Chai
authors.affiliation: Department of Clinical Pharmacology, PLA General Hospital, 28 Fu Xing Road, Beijing 100853, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Translational Medical Center, PLA General Hospital, 28 Fu Xing Road, Beijing 100853, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, PLA General Hospital, 28 Fu Xing Road, Beijing 100853, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Translational Medical Center, PLA General Hospital, 28 Fu Xing Road, Beijing 100853, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cai
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D018441:Biofilms / Q000187:drug effects*; D055499:Catheter-Related Infections / Q000188:drug therapy*; D002404:Catheterization; D004338:Drug Combinations; D004347:Drug Interactions; D005578:Fosfomycin / Q000008:administration & dosage*; D000069349:Linezolid / Q000008:administration & dosage*; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D005578:Fosfomycin; D000069349:Linezolid