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Left ventricular assist devices (LVAD) are increasingly used for management of heart failure; infection remains a frequent complication. Phage therapy has been successful in a variety of antibiotic refractory infections and is of interest in treating LVAD infections. We performed a retrospective review of four patients that underwent five separate courses of intravenous (IV) phage therapy with concomitant antibiotic for treatment of endovascular Pseudomonas aeruginosa LVAD infection. We assessed phage susceptibility, bacterial strain sequencing, serum neutralization, biofilm activity, and shelf-life of phage preparations. Five treatments of one to four wild-type virulent phage(s) were administered for 14-51 days after informed consent and regulatory approval. There was no successful outcome. Breakthrough bacteremia occurred in four of five treatments. Two patients died from the underlying infection. We noted a variable decline in phage susceptibility following three of five treatments, four of four tested developed serum neutralization, and prophage presence was confirmed in isolates of two tested patients. Two phage preparations showed an initial titer drop. Phage biofilm activity was confirmed in two. Phage susceptibility alone was not predictive of clinical efficacy in P. aeruginosa endovascular LVAD infection. IV phage was associated with serum neutralization in most cases though lack of clinical effect may be multifactorial including presence of multiple bacterial isolates with varying phage susceptibility, presence of prophages, decline in phage titers, and possible lack of biofilm activity. Breakthrough bacteremia occurred frequently (while the organism remained susceptible to administered phage) and is an important safety consideration.

Using phages as salvage therapy for nonhealing infections is gaining recognition as a viable solution for patients with such infections. The escalating issue of antibiotic resistance further emphasizes the significance of using phages in treating bacterial infections, encompassing compassionate-use scenarios and clinical trials. Given the high specificity of phages, selecting the suitable phage(s) targeting the causative bacteria becomes critical for achieving treatment success. However, in contrast to conventional antibiotics, where susceptibility-testing procedures were well established for phage therapy, there is a lack of standard frameworks for matching phages from a panel to target bacterial strains and assessing their interactions with antibiotics or other agents. This review discusses and compares published methods for clinical phage microbiology, also known as phage susceptibility testing, and proposes guidelines for establishing a standard pipeline based on our findings over the past 5 years of phage therapy at the Israeli Phage Therapy Center. [ABSTRACT FROM AUTHOR]

Background: Phage therapy offers a promising alternative for treating serious infections, including diabetic foot ulcers (DFUs), through the lytic action of phages. This randomized double-blind study was conducted to evaluate the safety and tolerability of the TP-102 bacteriophage cocktail in patients with DFUs non-infected and infected with Staphylococcus aureus, Pseudomonas aeruginosa, and/or Acinetobacter baumannii., Methods: Nineteen participants with DFUs were randomized after susceptibility testing. TP-102 was applied topically at 10⁹ plaque-forming units (PFUs)/mL/cm³ to the target ulcer: 1 week for non-infected DFUs and 28 days for infected DFUs (PEDIS grade 2/3). The study was conducted in Israel., Findings: Main outcomes included the incidence and severity of TP-102-related adverse events, microbiological data, and ulcer healing. Thirteen patients received TP-102. No treatment-related adverse events were reported. Although the study was underpowered to determine the superiority of TP-102 over placebo, a greater proportion of patients in the TP-102 + standard of care (SOC) group showed microbiological reduction of target bacteria (t = 26) compared to the placebo + SOC group (80% versus 50%, p = 1.000). Additionally, a higher proportion of TP-102 patients reached 50% and 75% wound closure compared to placebo (5/7 [71.4%] versus 1/3 [33.3%], p = 0.500 and 2/7 [28.6%] versus none, p = 1.000, respectively). One patient in the TP-102 group achieved wound closure., Conclusions: TP-102 was well tolerated and safe, showing potential as a groundbreaking treatment in this field. Further studies are needed to confirm its safety and efficacy in larger populations with diabetic foot infections (ClinicalTrials.gov: NCT04803708)., Funding: None to declare., Competing Interests: Declaration of interests R.N.-P. has been a scientific consultant for BiomX and has participated in and served as a PI and on data safety monitoring boards for a clinical trial by Technophage. R.B.-A. has actively contributed to clinical boards with GlaxoSmithKline and Merck Sharp and has also been involved in lecturing events associated with Teva and Gilead Sciences. S.C.-R. and C.L. participated in a clinical trial by Technophage as cohort escalation committee and safety review committee members, respectively; they are inventors in Technophage’s patents. M.G. is a board member of Technophage S.A., Vector B2B, and LxBio Pharmaceuticals S.A., (Copyright © 2024 Elsevier Inc. All rights reserved.)