Jessica Sacher, editor-in-chief of the weekly online publication Capsid & Tail , spoke about the challenges of treating infected foot ulcers in patients with diabetes, as well as the possibilities of phage therapy for this pathology.

Every 20 seconds, someone worldwide loses a limb due to complications of diabetes. Foot or toe ulcers, which are common in patients with diabetes, are a common cause of amputations. In approximately half of cases, foot/toe ulcers become infected, but antibiotic treatment is not always effective. Limb amputation significantly increases the risk of death within a few years.

There are several reasons why antibiotics are ineffective in treating foot ulcers associated with diabetes. Specifically, antimicrobials are unable to penetrate the wound due to poor blood supply to the extremities and are unable to reach bacteria due to the formation of biofilms. One of the main pathogens associated with diabetic foot infections is Staphylococcus aureus , an opportunistic bacterium that often exhibits antibiotic resistance.

Foot ulcers in diabetic patients are promising candidates for phage therapy because they are easily treated, poorly with antibiotics, and the wound healing process is easy to monitor. For this reason, phage therapy for infected diabetic feet has already been tested in both animals [1] and humans [2].

Clinical cases indicate that phage therapy promotes wound healing and reduces the risk of amputation (six clinical cases of phage therapy of infected foot ulcers in patients with diabetes are described in [3]).

Read also: Clinical case: Phage therapy of infected diabetic foot

Randomized clinical trials

The Portuguese company TechnoPhage has initiated Phase I/IIa clinical trials of phage therapy for infected diabetic foot infections. The study is investigating the safety and tolerability of candidate phage preparations specific for P. aeruginosa , S. aureus , and A. baumannii , as well as their ability to reduce the number of target bacteria. Results are expected in 2021 .

In the near future, the University of Nîmes (France), in collaboration with Pherecydes Pharma, will launch the PhagoPied study, which will compare the efficacy, safety, and tolerability of standard treatment + anti-staphylococcal bacteriophages with standard treatment + placebo in 60 patients with foot ulcers associated with diabetes.

In addition, the University Hospitals Derby and Burton NHS Foundation Trust announced clinical trials of the use of anti-staphylococcal phages in the treatment of foot ulcers in patients with diabetes.

J. Sucher invites all specialists developing phage therapy methods for diabetic foot ulcers to join forces. A virtual roundtable discussion is planned to explore opportunities for collaboration (interested physicians and scientists can contact jessica@phage.directory).

Literature

1. Duplessis CA, Biswas B. A Review of Topical Phage Therapy for Chronically Infected Wounds and Preparations for a Randomized Adaptive Clinical Trial Evaluating Topical Phage Therapy in Chronically Infected Diabetic Foot Ulcers. Antibiotics. 2020; 9(7):377. https://doi.org/10.3390/antibiotics9070377

2. Kifelew LG, Warner MS, Morales S et al. Efficacy of phage cocktail AB-SA01 therapy in diabetic mouse wound infections caused by multidrug-resistant Staphylococcus aureus. BMC Microbiol. 2020; 20:204. https://doi.org/10.1186/s12866-020-01891-8

3. Fish R, Kutter E, Wheat G et al. Bacteriophage treatment of intransigent diabetic toe ulcers: a case series. Journal of Wound Care. 2016; 25:Sup7, S27-S33. https://doi.org/10.12968/jowc.2016.25.Sup7.S27