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

Autor:	Thompson MG; Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Truong-Le V; Aridis Pharmaceuticals LLC, San Jose, California, USA., Alamneh YA; Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Black CC; Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Anderl J; Aridis Pharmaceuticals LLC, San Jose, California, USA., Honnold CL; Department of Pathology, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Pavlicek RL; Department of Wound Infections, Naval Medical Research Center, Silver Spring, Maryland, USA., Abu-Taleb R; Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Wise MC; Department of Pathology, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Hall ER; Department of Wound Infections, Naval Medical Research Center, Silver Spring, Maryland, USA., Wagar EJ; Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Patzer E; Aridis Pharmaceuticals LLC, San Jose, California, USA., Zurawski DV; Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA daniel.v.zurawski.ctr@mail.mil.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2015 Oct; Vol. 59 (10), pp. 6484-93. Date of Electronic Publication: 2015 Aug 03.
DOI:	10.1128/AAC.00882-15
Abstrakt:	Skin and soft tissue infections (SSTIs) are a common occurrence in health care 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 MIC against K. pneumoniae ranged from 0.125 to 2.0 μg/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 following inoculation, and a 0.5 to 1.5 log reduction of CFU was observed. Lastly, upon scanning electron microscopy analysis, GaCi treatment appeared to prevent biofilm formation on dressings compared to those of untreated controls. These results suggest that with more preclinical testing, a topical application of GaCi may be a promising alternative treatment strategy for K. pneumoniae SSTI. (Copyright © 2015 Thompson et al.)
Databáze:	MEDLINE
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