Bacteriophages in the Treatment of Infected Diabetic Foot: State of the Art
Jessica Sacher, Editor-in-Chief, Online Weekly Capsid & Tail, discussed the challenges of treating infected foot ulcers in patients with diabetes mellitus and the potential of phage therapy for this pathology
Every 20 seconds, a person in the world loses a limb due to complications from diabetes. Amputations are often caused by foot or toe ulcers, which are common in diabetics. In approximately half of cases, foot/toe ulcers are infected, but antibiotic treatment is not always effective. Limb amputation significantly increases the risk of death over several years.
There are several reasons for the ineffectiveness of antibiotics in treating foot ulcers in diabetes mellitus. In particular, antimicrobial drugs may not penetrate the wound due to poor blood supply to the extremities and may not reach bacteria due to biofilm formation. One of the main pathogens of infected diabetic foot is the opportunistic bacterium Staphylococcus aureus, which frequently exhibits antibiotic resistance.
Foot ulcers in diabetics are promising candidates for phage therapy because they are easily accessible for treatment, difficult to treat with antibiotics, and the wound healing process is easy to observe. For this reason, phage therapy for infected diabetic foot has already been tested in both animals [1] and humans [2].
Clinical cases indicate that phage therapy supports wound healing and reduces the risk of amputation (six clinical cases of phage therapy for infected foot ulcers in diabetics are described in [3]).
Randomized Clinical Trials
Phase I/IIa clinical trials for phage therapy in infected diabetic foot were initiated by the Portuguese company TechnoPhage. They are investigating the safety and tolerability of candidate phage preparations against specific P. aeruginosa, S. aureus, 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 begin 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 in the context of diabetes mellitus.
In addition, the Derby and Burton NHS Foundation Trust announced clinical trials with anti-staphylococcal phages for the treatment of foot ulcers in patients with diabetes.
J. Sacher invites all specialists developing phage therapy methods for diabetic foot ulcers to join forces. A virtual roundtable on this topic is planned to identify opportunities for collaboration (interested physicians and scientists can write to jessica@phage.directory).
References
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 intractable 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
