title: Evaluation of Gallium Citrate Formulations against a Multidrug-Resistant Strain of Klebsiella pneumoniae in a Murine Wound Model of Infection.
abstract: 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.
authors.affiliation: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Mitchell G
authors.initials: MG
authors.lastname: Thompson
authors.affiliation: Aridis Pharmaceuticals LLC, San Jose, California, USA.
authors.forename: Vu
authors.initials: V
authors.lastname: Truong-Le
authors.affiliation: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Yonas A
authors.initials: YA
authors.lastname: Alamneh
authors.affiliation: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Chad C
authors.initials: CC
authors.lastname: Black
authors.affiliation: Aridis Pharmaceuticals LLC, San Jose, California, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Anderl
authors.affiliation: Department of Pathology, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Cary L
authors.initials: CL
authors.lastname: Honnold
authors.affiliation: Department of Wound Infections, Naval Medical Research Center, Silver Spring, Maryland, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Pavlicek
authors.affiliation: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Rania
authors.initials: R
authors.lastname: Abu-Taleb
authors.affiliation: Department of Pathology, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Wise
authors.affiliation: Department of Wound Infections, Naval Medical Research Center, Silver Spring, Maryland, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Hall
authors.affiliation: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Wagar
authors.affiliation: Aridis Pharmaceuticals LLC, San Jose, California, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Patzer
authors.affiliation: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA daniel.v.zurawski.ctr@mail.mil.
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Zurawski
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002951:Citrates / Q000494:pharmacology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D005260:Female; D005708:Gallium / Q000494:pharmacology*; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000254:growth & development; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D018461:Soft Tissue Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects; D014946:Wound Infection / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D002951:Citrates; D005708:Gallium; C103850:gallium citrate