Efficacy of combined vancomycin and fosfomycin against methicillin-resistant Staphylococcus aureus in biofilms in vivo

• Published in: PloS one Vol. 9; no. 12; p. e113133
• Main Authors: Shi, Jian, Mao, Ning-Fang, Wang, Li, Zhang, Han-Bo, Chen, Qian, Liu, Hua, Tang, Xun, Jin, Tao, Zhu, Chong-Tao, Li, Fu-Bing, Sun, Lin-Hui, Xu, Xin-Ming, Xu, Yong-Qing
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.12.2014; Public Library of Science (PLoS)
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotics; Antimicrobial agents; Bacteria; Biofilms; Biofilms - drug effects; Biology and Life Sciences; Blood; C-reactive protein; C-Reactive Protein - metabolism; Carboxymethyl cellulose; Carboxymethylcellulose; Cellulose; Chemotherapy; Chronic infection; Cystic fibrosis; Drug resistance; Drug Synergism; Endocarditis; Exudates; Exudation; Fosfomycin; Fosfomycin - pharmacology; Fosfomycin - therapeutic use; In vivo methods and tests; Infectious diseases; Laboratories; Leukocyte Count; Leukocytes; Male; Methicillin; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - physiology; Microbial Sensitivity Tests; Minimum inhibitory concentration; Morphology; Orthopedics; Pathogens; Peripheral blood; Rats; Rats, Sprague-Dawley; Staphylococcal Infections - blood; Staphylococcal Infections - drug therapy; Staphylococcus aureus; Staphylococcus epidermidis; Staphylococcus infections; Studies; Therapy; Vancomycin; Vancomycin - pharmacology; Vancomycin - therapeutic use
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0113133

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.