Efficacy testing of topical delivered moxifloxacin against MRSA in a porcine wound infection model

Abstract

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of infections in wounds and associated with high morbidity [1]. The emergence of bacterial resistance to multiple antibiotics [2] has led to an increased urgency to develop new therapeutic options for wound infections. The aim of this study was to assess the antimicrobial activity of moxifloxacin in a preclinical large animal model of MRSA wound infection. Methods: Six full thickness BO-wound chambers [3] were implanted on each flank of 2 female Goettingen minipigs under general anaesthesia. 7 days after implantation wounds were inoculated with 1 × 108 colony forming units (cfu) of MRSA. After wound infection had been established and quantified (3 days after inoculation), wounds were randomised and topically treated with either placebo-gel (carrier-control n = 7), 0.1 % linezolid (n = 3), 0.1 % mupirocin (n = 3), 2 % mupirocin (commercial ointment; n = 4) or 0.1 % moxifloxacin (n = 7). Topical treatment and wound fluid collection was carried out every other day for 2 weeks for quantitative bacterial analysis to monitor wound infection. Animals were photographed every day to document macroscopic signs of infection. The animals were sacrificed 21 days post-inoculation and tissue biopsies were taken for histological analysis and quantitative bacterial counts. Results: No macroscopic difference was seen between the active treatment groups, whereas pus accumulation was seen in the carrier control group. Pre-treatment all wounds showed a high and stable bacterial infection (> 105 cfu/ml wound fluid). Antibiotic therapy with linezolid, mupirocin and moxifloxacin significantly reduced bacterial counts in wound fluid and tissue in contrast to the carrier control. Moxifloxacin showed a strong antimicrobial activity (with up to 103 reduction in bacterial counts) compared to carrier control (fluid p = 0.012, tissue p = 0.013). Linezolid and mupirocin showed comparable results. Conclusion: All antibiotics showed high efficacy towards MRSA infection in this porcine full-thickness wound infection model. The activity of moxifloxacin is comparable to that of clinically used antibiotics (linezolid, mupirocin) and no side effects were observed. Moxifloxacin has promise to be a potential new therapeutic option for the treatment of MRSA wound infection.