Chronic wounds are projected to reach epidemic proportions worldwide because of the aging population and the increasing incidence of diabetes. Despite extensive research, infection remains one of the leading sources of complications in chronic wounds, resulting in improper healing, biofilm formation, and lower extremity amputation. To address the limitations of standard treatments, we have developed a hydrogel wound dressing with self-tuning moisture control that incorporates a novel antimicrobial agent to eliminate and prevent infection. 3D-printing of a hydrogel dressing with dual porosity resulted in a new dressing with greater flexibility, increased water uptake, and more rapid swelling than bulk hydrogel dressings. Additionally, gallium maltolate (GaM) was incorporated into the dressing to investigate the efficacy of this antimicrobial agent. Loading profiles, release kinetics, and the bactericidal activity against Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus ) of GaM were investigated in vitro to identify target profiles that supported infection control. Finally, GaM-loaded hydrogel dressings were evaluated in vivo , utilizing a murine splinted-wound model that was inoculated with S. aureus . In comparison to an untreated control, GaM dressings markedly reduced the wound bacterial load without compromising wound closure rates. Overall, this work demonstrates the utility of a 3D-printed hydrogel dressing as an antimicrobial dressing to control infection in chronic wounds.
Rhodococcus equi can cause severe infections in people, particularly in immunocompromised individuals. The R. equi virulence plasmids (vap) encoding vapA and vapB are linked to development of infections in domestic animals. Recently, a novel virulence plasmid, vapN, was identified in isolates cultured from cattle, but its prevalence or significance in human R. equi infections has not been extensively studied. To determine the prevalence of vapN in a diverse collection of human-derived isolates from different countries, 65 R. equi isolates collected by various institutions from 1984 to 2002 were screened for the presence of vapN and other virulence plasmids through polymerase chain reaction (PCR) using redesigned primer sets. Of the isolates that carried plasmids, 43% (16/37) were vapN-positive and fewer were vapB or vapA-positive (30 and 16%, respectively). This is the first report of vapN carriage in R. equi isolated from human infections. One isolate (H-30) carried vapN but did not amplify the conjugal plasmid transfer gene traA associated with carriage of vap, which could be explained by sequence variation within the traA gene. Another isolate (H-55) amplified traA, but did not amplify vapA, B, or N (traA+ vapABN-) with previously described primer sets or those developed for this study. The H-55 traA sequence had 98% identity to traA sequences in vapA plasmids, which suggests that it may carry a variant of previously characterized virulence plasmids or a novel virulence plasmid. Carriage of vapN in R. equi isolates derived from people is not uncommon and more research is needed to determine its significance in the epidemiology and pathogenesis of human R. equi infections.
and the fifth sentence of the first paragraph of the Discussion are incorrect. The vapN carriage of R. equi isolated from human infections from Brazil was reported during the revision process of this article [2] and an isolate from Japan has been previously identified [3]. The two sentences in question were not corrected between revisions.
Rhodococcus equi is an opportunistic intracellular pathogen that causes pyogranulomatous pneumonia in foals and immunocompromised people, and is clinically and microbiologically similar to tuberculosis (TB). Currently, no model exists of R. equi pneumonia other than intra-bronchial infection of foals with R. equi. Because infection of foals is labor-intensive and costly, a guinea pig (GP) model of R. equi pneumonia would be of great benefit for evaluating novel approaches for control and prevention of this disease (and possibly TB). Our objective in this study was to develop a GP model of R. equi pneumonia. Groups of 6 GPs were infected with either 101, 102, 103, or 104 CFU of virulent R. equi strain using a Madison aerosol chamber, and groups of 6 GPs were infected with either 106, 107, or 108 CFU of virulent R. equi intratracheally. GPs were observed daily for clinical signs of pneumonia, and were euthanized on days 1, 3, 7, 14, or 35 post-infection (PI). Necropsy was performed and lungs were weighed, homogenized with PBS, and plated onto selective agar to determine bacterial load. No clinical signs of the disease or gross pathologic changes were observed regardless of the inoculum or mode of infection; histopathological findings of lungs are pending. Viable bacteria recovered from the lungs increased on day 3 PI, but decreased on day 7. No bacteria were recovered from animals euthanized either 2 or 5 weeks PI. Despite being highly susceptible to the agent of TB, GPs appear to be resistant to pulmonary infection with virulent R. equi at high doses. These remarkable findings suggest that this model might reveal novel mechanisms of resistance to natural infection with R. equi, which could inform the development of prophylactic or therapeutic approaches.
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