Bacteriophage Application for Difficult-To-Treat Musculoskeletal Infections: Development of a Standardized Multidisciplinary Treatment Protocol

Abstract

Bacteriophage therapy has recently attracted increased interest, particularly in difficult-to-treat infections. Although it is not a novel concept, standardized treatment guidelines are currently lacking. We present the first steps towards the establishment of a “multidisciplinary phage task force” (MPTF) and a standardized treatment pathway, based on our experience of four patients with severe musculoskeletal infections. After review of their medical history and current clinical status, a multidisciplinary team found four patients with musculoskeletal infections eligible for bacteriophage therapy within the scope of Article 37 of the Declaration of Helsinki. Treatment protocols were set up in collaboration with phage scientists and specialists. Based on the isolated pathogens, phage cocktails were selected and applied intraoperatively. A draining system allowed postoperative administration for a maximum of 10 days, 3 times per day. All patients received concomitant antibiotics and their clinical status was followed daily during phage therapy. No severe side-effects related to the phage application protocol were noted. After a single course of phage therapy with concomitant antibiotics, no recurrence of infection with the causative strains occurred, with follow-up periods ranging from 8 to 16 months. This study presents the successful outcome of bacteriophage therapy using a standardized treatment pathway for patients with severe musculoskeletal infection. A multidisciplinary team approach in the form of an MPTF is paramount in this process.

Salvage Bacteriophage Therapy for a Chronic MRSA Prosthetic Joint Infection

“…This surgery allows for manual scrubbing of biofilm, ensures that the prosthesis is salvable, and allows instilment of bacteriophages directly to the biofilm. Local dosing of bacteriophages may be vital to clear biofilm infections, but limited data beyond case reports is available [10][11][12]. No adverse events occurred with repeated IA doses, which may be due to limited systemic absorption.…”

Targeting Plasmids to Limit Acquisition and Transmission of Antimicrobial Resistance

“…Schooley et al (2017) have used phagotherapy in a patient with necrotic pancreatitis caused by a MDR strain of A. baumannii. Other studies have obtained favorable results for the phagotherapy of an aortic graft infection with P. aeruginosa (Chan et al, 2018), pneumonia caused by a MDR strain of P. aeruginosa in a cystic fibrosis patient (Law et al, 2019), a Mycobacterium abscessus infection in a patient with cystic fibrosis (Dedrick et al, 2019), and periprosthetic, musculoskeletal, and lung infections (Maddocks et al, 2019;Onsea et al, 2019;Tkhilaishvili et al, 2019). Contrary to these studies, there are reports of the inefficiency of phages in treating bacterial infections (Sarker et al, 2016;Jault et al, 2019), which suggests that the clinical use of phages requires standardization.…”

Local Bacteriophage Delivery for Treatment and Prevention of Bacterial Infections

“…Depending on the application, release kinetics of phages from a biomaterial matrix can be tuned by the biomaterial type and implant design (e.g., films, particles or hydrogels). Phage loading inside biomaterials (up to 10 11 PFU/mL) often exceeds the phage concentration used in recently proposed phage treatment protocols for non-topical infections [10 7 PFU/mL, with rinsing volumes ranging from 10 to 40 mL (Chan et al, 2018;Onsea et al, 2019)]. Due to the high phage load of biomaterials, a sustained release of loaded phage is achievable and may be beneficial in order to maintain a prolonged therapeutic activity of released phage.…”