Comparative study on the wound healing effects of local versus systemic application of Polymyxin B in mice infected with multidrug-resistant Pseudomonas aeruginosa

Background Wound infections caused by extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) pose a significant clinical challenge with extremely limited treatment options. Polymyxin B (PMB) represents one of the last therapeutic lines of defence, yet its optimal route of administration (topical, intravenous, or combined) for deep tissue infections such as wounds remains to be further investigated. Objective This study aimed to investigate the efficacy differences of different PMB administration routes (topical, intravenous, and combined therapy) in treating XDR-PA wound infections in mice, providing experimental evidence for optimizing clinical treatment regimens. Methods One hundred and twenty Kunming mice were randomly assigned to five groups ( n = 24 per group): (1) sham-operated group (uninfected); (2) infected untreated group; (3) infected + topical administration group (5 mg/kg); (4) Infection + intravenous administration group (5 mg/kg); (5) Infection + combined topical and intravenous administration group (2. 5 mg/ kg each). A full-thickness dorsal skin defect wound infection model was established in mice. Drug administration was in initiated 24 h post- infection and was performed once daily for four consecutive days. Daily observations and recordings were made of mouse body weight changes and wound erythema. Every 4 days post-infection, three mice were randomly selected and euthanized from each group for wound tissue collection to determine bacterial load. On days 6 and 17, wound tissue was collected for protein content analysis, cytokine (e.g., IL-1β, TNF- α ) detection, and histopathological assessment. Results Compared to the untreated infected group, all administered treatment groups demonstrated therapeutic efficacy. The topical administration group exhibited the most pronounced wound healing promotion, it achieved the highest wound closure rate, fastest resolution of erythema and oedema, and optimal bacterial clearance efficiency. Additionally, it showed effective regulation of inflammatory response, and minimal histopathological damage. The intravenous administration group exhibited the next highest efficacy. The combination therapy group did not demonstrate synergistic effects superior to local monotherapy. Mice in the untreated infection group exhibited the slowest weight gain and delayed wound healing. Mice in the untreated infection group exhibited the slowest weight loss and delayed wound healing. Discussion (Conclusion) Under the experimental conditions employed, topical application of PMB demonstrated superior efficacy to intravenous administration and combined therapy in treating wound infections in XDR-PA mice. Due to the equal total daily dose design (5 mg/kg for all treatment groups), the combination therapy group received a lower dose per route (2.5 mg/kg each) compared to the monotherapy groups (5 mg/kg via a single route). Therefore, no definitive conclusion can be drawn regarding potential synergistic or antagonistic effects of combination therapy based on this study design. This suggests that targeted local administration may represent a more effective and cost-efficient strategy for localized infections caused by resistant bacteria, which warrants further clinical translational research.