Phage Therapy for Diabetic Foot Infection: A Case Series.

PURPOSE: Infected diabetic foot ulcers can be difficult to treat and, despite appropriate antibiotic therapy, some diabetic foot infections (DFIs) require amputation. Bacteriophages (phages) are viruses that infect and kill bacteria. Phage therapy has been repeatedly used to successfully treat DFIs and other chronic wounds. METHODS: This article reports the provision of topical adjunctive anti-staphylococcal phage therapy to 10 patients with DFI at high risk of amputation at two UK hospitals as part of clinical care; tolerability and efficacy were clinically assessed. FINDINGS: The opinion of the experienced clinical teams caring for these patients was that 9 of the 10 patients appeared to benefit from adjunctive phage therapy. No adverse effects were reported by clinicians or patients. In 6 of 10 patients the clinical impression was that phage therapy facilitated clinical resolution of infection and limb salvage. Resolution of soft tissue infection was observed in a 7th patient but unresolved osteomyelitis required amputation. An 8th patient demonstrated eradication of Staphylococcus aureus from a polymicrobial infection and a 9th showed signs of clinical improvement before early cessation of phage therapy due to an unrelated event. One patient, with a weakly susceptible S aureus isolate, had no significant response. IMPLICATIONS: This report describes the largest application of phage therapy in the United Kingdom to date and the first application of phage therapy for DFI in the United Kingdom and offers subjective hints toward impressive tolerability and efficacy. Phage therapy has the potential to transform the prevention and treatment of DFIs.

Patient perceptions of phage therapy for diabetic foot infection.

Infections of diabetic foot ulcers are common, generally recalcitrant and often complicated by antibiotic resistance. Alternative antimicrobial strategies are needed. Phage therapy is a promising alternative that is being rediscovered. Despite phage therapy's 100-year history, there have been no investigations into patient thoughts and concerns. This study aimed to explore patient awareness of and concern about antibiotic resistance and gain insight into the perceptions of phage therapy among a patient group that could potentially benefit from phage therapy. Patients with an active or resolved (healed or amputated) diabetic foot ulcer were eligible to participate. A survey was distributed digitally to eligible patients across Scotland via the NHS Research Scotland Diabetes Network and hard copies were available in diabetic foot clinics at the Royal Infirmary of Edinburgh and Queen Elizabeth University Hospital, Glasgow. A focus group of five survey respondents was held in Glasgow. Fifty-five survey responses were obtained. There was a high level of awareness (76.4%; N = 55) and concern (83.3%; N = 54) about antibiotic resistance. While largely aware of viruses, most patients had not heard of phage or phage therapy. Patients were no more concerned about phage than antibiotic therapy, with most suggesting more information could alleviate any concerns. Patient acceptability of phage therapy was high, a finding confirmed by the focus group. Patients are concerned about antibiotic resistance and supportive of 'new' antimicrobials. We have demonstrated that patients are supportive, enthusiastic and accepting of phage therapy. Although 'Western' phage therapy remains in its infancy, an understanding of patient ideas, concerns and expectations will be important in eventually shaping and successfully reintroducing phage therapy.

A retrospective analysis of the microbiology of diabetic foot infections at a Scottish tertiary hospital.

BACKGROUND: This study represents the first Scottish retrospective analysis of the microbiology of diabetic foot infections (DFIs). The aims were to compare the microbiological profile of DFIs treated at a Scottish tertiary hospital to that in the literature, gather data regarding antimicrobial resistance and investigate potential trends between the microbiological results and nature or site of the clinical sample taken and age or gender of the patients. METHODS: A retrospective analysis of wound microbiology results was performed, data were obtained from one multidisciplinary outpatient foot clinic during the 12 months of the year 2017. Seventy-three patients and 200 microbiological investigations were included. In cases of soft tissue infection, the deepest part of a cleansed and debrided wound was sampled. In cases of osteomyelitis a bone biopsy was obtained. Factors influencing the pattern of microbial growth or prevalence of Staphylococcus aureus were investigated. RESULTS: Of the 200 microbiological investigations, 62% were culture positive, of which 37.9% were polymicrobial and 62.1% monomicrobial. Among the monomicrobial results (n = 77), most were Gram positive isolates (96.1%) and the most frequently isolated bacteria was S. aureus (84.4%). No methicillin-resistant S. aureus was reported. The prevalence of S. aureus in DFIs was associated with increasing age (p = 0.021), but no evidence of association with gender, anatomical sample site or sample material was found. CONCLUSION: The microbiological profile of DFIs in Scotland resembles that reported elsewhere in the UK. In this context, Gram positive organisms, primarily S. aureus, are most frequently isolated from DFIs. The S. aureus isolates identified were largely susceptible to antibiotic therapy. An association between increasing patient age and the prevalence of S. aureus in DFIs was observed.

Fat oxidation, fitness and skeletal muscle expression of oxidative/lipid metabolism genes in South Asians: implications for insulin resistance?

BACKGROUND: South Asians are more insulin resistant than Europeans, which cannot be fully explained by differences in adiposity. We investigated whether differences in oxidative capacity and capacity for fatty acid utilisation in South Asians might contribute, using a range of whole-body and skeletal muscle measures. METHODOLOGY/PRINCIPAL FINDINGS: Twenty men of South Asian ethnic origin and 20 age and BMI-matched men of white European descent underwent exercise and metabolic testing and provided a muscle biopsy to determine expression of oxidative and lipid metabolism genes and of insulin signalling proteins. In analyses adjusted for age, BMI, fat mass and physical activity, South Asians, compared to Europeans, exhibited; reduced insulin sensitivity by 26% (p = 0.010); lower VO2max (40.6±6.6 vs 52.4±5.7 ml x kg(-1) x min(-1), p = 0.001); and reduced fat oxidation during submaximal exercise at the same relative (3.77±2.02 vs 6.55±2.60 mg x kg(-1) x min(-1) at 55% VO2max, p = 0.013), and absolute (3.46±2.20 vs 6.00±1.93 mg x kg(-1) x min(-1) at 25 ml O(2) x kg(-1) x min(-1), p = 0.021), exercise intensities. South Asians exhibited significantly higher skeletal muscle gene expression of CPT1A and FASN and significantly lower skeletal muscle protein expression of PI3K and PKB Ser473 phosphorylation. Fat oxidation during submaximal exercise and VO2max both correlated significantly with insulin sensitivity index and PKB Ser473 phosphorylation, with VO2max or fat oxidation during exercise explaining 10-13% of the variance in insulin sensitivity index, independent of age, body composition and physical activity. CONCLUSIONS/SIGNIFICANCE: These data indicate that reduced oxidative capacity and capacity for fatty acid utilisation at the whole body level are key features of the insulin resistant phenotype observed in South Asians, but that this is not the consequence of reduced skeletal muscle expression of oxidative and lipid metabolism genes.