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.
Highlights
Antibiotics have played a major role in fighting infectious diseases, uncontrolled long-term or inappropriate use of antibiotics results in drug resistance and tolerant strains
A rat carboxymethyl cellulose (CMC)-pouch biofilm model was used to evaluate the in vivo bactericidal effects of VAN and FOS administered alone or in combination against biofilm-infected Methicillin-resistant Staphylococcus aureus (MRSA) and S. epidermidis
Bactericidal effects were observed in the combination therapy
Summary
Antibiotics have played a major role in fighting infectious diseases, uncontrolled long-term or inappropriate use of antibiotics results in drug resistance and tolerant strains. Methicillin-resistant Staphylococcus aureus (MRSA) is undoubtedly one of the most prevalent and notorious examples of an antibiotic-resistant pathogen [1]. Facing the risk of severe MRSA epidemic, an increasing interest is aroused in uncovering the mechanisms of drug resistance and discovering new antibiotics and regimens to treat resistant strains. A defining characteristic of MRSA is its ability to thrive in the presence of penicillin-like antibiotics, which normally inhibit the synthesis of the cell wall [1]. Resistance is mediated by the mecA gene, which stops b-lactam antibiotics from inactivating the enzymes (transpeptidases) critical for cell wall synthesis. In the process of infection, S. aureus often attaches to host tissue or the surface of implants, and gradually forms a biofilm structure [6]. After biofilm formation, bacterial resistance to host immune responses and antibiotics can increase greatly. Bacteria in biofilms are up to 1000 times less sensitive than planktonic bacteria to antibiotics [7, 8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
