Abstract

ABSTRACTDiabetic foot ulcers are notoriously difficult to heal, with ulcers often becoming chronic, in many cases leading to amputation despite weeks or months of antibiotic therapy in addition to debridement and offloading. Alternative wound biofilm management options, such as topical rather than systemic delivery of antimicrobials, have been investigated by clinicians in order to improve treatment outcomes. Here, we collected blood and tissue from six subjects with diabetic foot infections, measured the concentrations of antibiotics in the samples after treatment, and compared the microbiota within the tissue before treatment and after 7 days of antibiotic therapy. We used an in vitro model of polymicrobial biofilm infection inoculated with isolates from the tissue we collected to simulate different methods of antibiotic administration by simulated systemic therapy or topical release from calcium sulfate beads. We saw no difference in biofilm bioburden in the models after simulated systemic therapy (representative of antibiotics used in the clinic), but we did see reductions in bioburden of between 5 and 8 logs in five of the six biofilms that we tested with topical release of antibiotics via calcium sulfate beads. Yeast is insensitive to antibiotics and was a component of the sixth biofilm. These data support further studies of the topical release of antibiotics from calcium sulfate beads in diabetic foot infections to combat the aggregate issues of infectious organisms taking the biofilm mode of growth, compromised immune involvement, and poor systemic delivery of antibiotics via the bloodstream to the site of infection in patients with diabetes.

Highlights

  • Diabetes mellitus is a major public health concern with an estimated prevalence of 451 million people living with the condition in 2017 [1]

  • There is some evidence that topical antibiotic agents in the form of dressings may improve healing of diabetic foot infections (DFIs) [26] and that there is no additional risk of adverse events when comparing topical treatments to systemic antibiotics; more work needs to be done in this area [26]

  • Data on the systemic antibiotics chosen for treatment was recorded and blood samples were collected at day 7

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Summary

Introduction

Diabetes mellitus is a major public health concern with an estimated prevalence of 451 million people living with the condition in 2017 [1]. Successful treatment of diabetic foot infections (DFIs) is poor, with a 1-year observational study reporting a 44.5% incidence of unhealed DFIs [4]. For these patients, 23.4% required revascularization or amputation, 4.3% exhibited ulcer. Peripheral arterial disease (PAD) is a causative factor in approximately 50% of all DFUs and leads to chronic ulcer presentation and further increased risk of ulcer infection [16, 17]. Observational and case studies have not found systemic toxicity from vancomycin-loaded calcium sulfate (CS) void fillers [23, 30], which have been used safely as a delivery vehicle for the local release of antibiotics [31] and have shown efficacy against biofilms in previous in vitro studies [25, 32, 33], further work is required to demonstrate efficacy in a clinical setting

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