Evaluation of gallium citrate formulations against a multidrug-resistant strain of Klebsiella pneumoniae in a murine wound model of infection.
Antimicrob Agents Chemother. 2015 Aug 3;
Authors: Thompson MG, Truong-Le V, Alamneh YA, Black CC, Anderl J, Honnold CL, Pavlicek RL, Abu-Taleb R, Wise MC, Hall ER, Wagar EJ, Patzer E, Zurawski DV
Skin and soft tissue infections (SSTIs) are a common occurrence in healthcare facilities with a heightened risk for immunocompromised patients. Klebsiella pneumoniae has been increasingly implicated as the bacterial agent responsible for SSTIs, and treatment can be challenging as more strains become multidrug-resistant (MDR). Therefore, new treatments are needed to counter this bacterial pathogen. Gallium complexes exhibit antimicrobial activity and are currently being evaluated as potential treatment 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 minimal inhibitory concentration against K. pneumoniae ranged from 0.125 to2.0 ug/mL GaCi. After this in vitro efficacy was established, two topical formulations with GaCi (0.1% w/v and 0.3% w/v) 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 was accompanied by reduced inflammation when compared to untreated controls. Similarly, quantitative indications of infection remediation such as reduced weight loss and wound area suggested that treatment improved outcome when compared to untreated controls. Bacterial burdens were measured one and three days following inoculation, and a 0.5 - 1.5 log reduction of colony forming units was observed. Lastly, upon scanning electron microscopy analysis, GaCi treatment appeared to prevent biofilm formation on dressings when compared to untreated controls. These results suggest that with more preclinical testing a topical application of GaCi could be a promising alternative treatment strategy for K. pneumoniae SSTI.
PMID: 26239978 [PubMed - as supplied by publisher]