Search

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]

A study was undertaken to evaluate the quality of the timber produced by Pinus elliottii × Pinus caribaea var. hondurensis (PECH) and the Pinus patula × Pinus tecunumanii low elevation (PPTL) and high elevation (PPTH) hybrids and their parent species for both kraft pulp and sawn-timber production. Trees were taken from unthinned tree improvement trials managed for pulpwood, ranging in age between 15 and 19 years. All sawn boards produced by study trees met the minimum wood density requirement for S5-grade structural timber (360 kg m−3), but approximately 17% of the boards failed to meet the other requirements for the grade, largely due to knot-related defects. Results of dynamic modulus of elasticity assessments performed on all of the boards suggested that a large percentage of boards would not meet the specified average stiffness (7 800 MPa). This was confirmed by the results of static bending tests performed on a subsample of boards. All boards tested for all species and hybrids met the required fifth percentile bending strength value for grade S7 (15.8 MPa) according to SANS 6122 (2008) specifications. The kraft pulping results indicated that the samples taken from the upper part of the stem yielded slightly better results on average than the samples representing the whole tree with respect to uniformity in the kappa vs charge and temperature, and yield vs kappa traits, with slight improvement of pulp yield (52% vs 50%) and some strength properties compared with whole tree pulping. Samples from the upper part of the stem had a close delignification rate in the 60-80 kappa range. The delignification rate for PPTL in the 60-80 kappa range was slower and the yield was slightly lower than P. patula (53.17% vs 52.72%) despite a higher kappa number. The pulp strengths short-span compressive test, breaking length and tearing strength of PECH were similar to those of P. elliottii, which were in turn generally lower than those of P. patula. The pulp strengths of PPTL and PPTH were similar to those of P. patula, whereas P. caribaea strengths were intermediate between those of P. patula and P. elliottii. With the exception of a slightly lower pulp yield, PPTL emerged as the best all-round hybrid for both pulp and sawn-timber properties. [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.)

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., Competing Interests: Saima Aslam: Research funding support from the Cystic Fibrosis Foundation, Armata Pharmaceuticals, Adaptive Phage Therapeutics, and Contrafect Inc. Consultant for BiomX and Phico Therapeutics. Medical advisory board for Pherecydes Pharma and Phiogen. Dwayne Roach: none. Mikeljon P. Nikolich: Royalty-bearing Biological Material License Agreement with Adaptive Phage Therapeutics exists now but work presented in this manuscript predated it. Patent PCT/US22/73852, METHOD OF TREATING DRUG RESISTANT ESKAPE PATHOGENS USING THERAPEUTIC BACTERIOPHAGES was filed, but work reported in this manuscript predated the filing. Biswajit Biswas: Navy Work Unit # A1417. Dr. Biswas has a patent "Bacteriophage compositions and methods of selection of components against specific bacteria" US patent #10357522, which was licensed before. Robert T Schooley: Consulting fees from GSK, LyseNtech. Kimberley A. Lilly-Bishop: none. Gregory K. Rice: none. Regina Z. Cer: none. Theron Hamilton: none. Mathew Henry: Mr. Henry has a patent 10357522 licensed. Tiffany Luong: none. Ann-Charlott Salabarria: none. Laura Sisk-Hackworth: none. Andrey A. Filippov: Pending Patent PCT/US22/73852, METHOD OF TREATING DRUG RESISTANT ESKAPE PATHOGENS USING THERAPEUTIC BACTERIOPHAGES Francois Lebreton: none. Lindsey Hall: none. Ran Nir-Paz: Consultant for BiomX; and has participated and served as a PI and on Data Safety Monitoring Board for a clinical trial by Technophage. Hadil Onalla: none. Gilat Livni: none. Eran Shostak: none. Anat Weider-Feinsod: none. Dafna Yahav: none. Ortal Yerushalmy: none. Sivan Alkalay-Oren: none. Leron Khalifa: none. Amit Rimon: none. Daniel Gelman: none. Ronen Hazan: none.