Evaluation of Gallium Citrate Formulations against a Multidrug- Resistant Strain of Klebsiella pneumoniae in a Murine Wound Model of Infection

Skin and soft tissue infections (SSTIs) are a common occurrence in health care facilities with a heightened risk for immunocom-promised patients. Klebsiella pneumoniae has been increasingly implicated as the bacterial agent responsible for SSTIs, and treatment can be challenging as more strains becomemultidrug resistant (MDR). Therefore, new treatments are needed to coun-ter this bacterial pathogen. Gallium complexes exhibit antimicrobial activity and are currently being evaluated as potential treat-ment for bacterial infections. In this study, we tested a topical formulation containing gallium citrate (GaCi) for the treatment of wounds infected with K. pneumoniae. First, the MIC against K. pneumoniae ranged from 0.125 to 2.0g/ml GaCi. After this in vitro efficacy was established, two topical formulations with GaCi (0.1 % [wt/vol] and 0.3 % [wt/vol]) were tested in a murine wound model of MDR K. pneumoniae infection. Gross pathology and histopathology revealed K. pneumoniae-infected wounds appeared to close faster with GaCi treatment and were accompanied by reduced inflammation compared to those of untreated controls. Similarly, quantitative indications of infection remediation, such as reduced weight loss and wound area, suggested that treatment improved outcomes compared to those of untreated controls. Bacterial burdens were measured 1 and 3 days fol-lowing inoculation, and a 0.5 to 1.5 log reduction of CFU was observed. Lastly, upon scanning electronmicroscopy analysis, GaCi treatment appeared to prevent biofilm formation on dressings compared to those of untreated controls. These results sug-gest that with more preclinical testing, a topical application of GaCi may be a promising alternative treatment strategy forK. pneumoniae SSTI