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.

Most commercially available vaccines are stored under refrigerated conditions, if not frozen. Such stringent storage conditions place a strain on the storage and transport of vaccines, in addition to the added complexities of mass vaccination campaigns in regions lacking sufficient cold chain storage. Although new vaccines are developed or re-engineered to improve safety and efficacy, the development of thermally stable vaccines has lagged behind. Development efforts to stabilize vaccines at room temperature include molecular/genetically engineered vaccines, formulation improvements, and process optimization. The advantages and disadvantages associated with each approach are presented, along with examples of vaccines that have been successfully stabilized. Recent developments in drug delivery technology are also presented, most of which require vaccines to be stabilized in the solid state. These novel delivery devices are expected to make improvements in the current treatments of infectious diseases by directly targeting the site of interest, thus eliminating systemic dosing and its associated complexities. The future of vaccine products, in addition to their method of production, is also discussed.