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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.

ABSTRACT: The advent and increasing prevalence of antimicrobial resistance commensurate with the absence of novel antibiotics on the horizon raises the specter of untreatable infections. Phages have been safely administered to thousands of patients exhibiting signals of efficacy in many experiencing infections refractory to antecedent antibiotics. Topical phage therapy may represent a convenient and efficacious treatment modality for chronic refractory infected cutaneous wounds spanning all classifications including venous stasis, burn-mediated, and diabetic ulcers. We will initially provide results from a systematic literature review of topical phage therapy used clinically in refractorily infected chronic wounds. We will then segue into a synopsis of the preparations for a forthcoming phase II a randomized placebo-controlled clinical trial assessing the therapeutic efficacy exploiting adjunctive personalized phage administration, delivered topically, intravenously (IV) and via a combination of both modalities (IV + topical) in the treatment of infected diabetic foot ulcers (perhaps the canonical paradigm representing complicated recalcitrant infected cutaneous wounds).

SUBMITTER: Duplessis CA

PROVIDER: S-EPMC7400337 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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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.

Duplessis Christopher Anthony CA Biswas Biswajit B

Antibiotics (Basel, Switzerland) 20200704 7

The advent and increasing prevalence of antimicrobial resistance commensurate with the absence of novel antibiotics on the horizon raises the specter of untreatable infections. Phages have been safely administered to thousands of patients exhibiting signals of efficacy in many experiencing infections refractory to antecedent antibiotics. Topical phage therapy may represent a convenient and efficacious treatment modality for chronic refractory infected cutaneous wounds spanning all classification ...[more]

PMID: 32635429

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Project description:BackgroundAccurate identification of primary pathogens in foot infections remains challenging due to the diverse microbiome. Conventional culture may show false-positive or false-negative growth, leading to ineffective postoperative antibiotic treatment. Next-generation sequencing (NGS) has been explored as an alternative to standard culture in orthopedic infections. NGS is highly sensitive and can detect an entire bacterial genome along with genes conferring antibiotic resistance in a given sample. We investigated the potential use of NGS for accurate identification and quantification of microbes in infected diabetic foot ulcer (DFU). We hypothesize that NGS will aid identification of dominant pathogen and provide a more complete profile of microorganisms in infected DFUs compared to the standard culture method.MethodsData were prospectively collected from 30 infected DFU patients who underwent operative treatment by a fellowship-trained orthopedic foot and ankle surgeon from October 2018 to September 2019. The average age of the patient was 60.4 years. Operative procedures performed were irrigation and debridement (12), toe or ray amputation (13), calcanectomies (4), and below-the-knee amputation (1). Infected bone specimens were obtained intraoperatively and processed for standard culture and NGS. Concordance between the standard culture and NGS was assessed.ResultsIn 29 of 30 patients, pathogens were identified by both NGS and culture, with a concordance rate of 70%. In standard culture, Staphylococcus aureus (58.6%) was the most common pathogen, followed by coagulase-negative Staphylococcus (24.1%), Corynebacterium striatum (17.2%), and Enterococcus faecalis (17.2%). In NGS, Finegoldia magna (44.8%) was the most common microorganism followed by S. aureus (41.4%), and Anaerococcus vaginalis (24.1%). On average, NGS revealed 5.1 (range, 1-11) pathogens in a given sample, whereas culture revealed 2.6 (range, 1-6) pathogens.ConclusionNGS is an emerging molecular diagnostic method of microbial identification in orthopedic infection. It frequently provides different profiles of microorganisms along with antibiotic-resistant gene information compared to conventional culture in polymicrobial foot infection. Clinical use of NGS for management of foot and ankle infections warrants further investigation.Level of evidenceLevel II, diagnostic study.

Dataset Information

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.

Publications

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.

Similar Datasets

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