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Objective: Staphylococcus aureus fracture-related infections (FRIs) are associated with significant morbidity in part because conventional antibiotic therapies have limited ability to eradicate S. aureus in sessile states. Therefore, the objective of this study was to assess the feasibility of using Staphylococcal bacteriophages for FRI by testing the activity of a library of Staphylococcal bacteriophage therapeutics against historically preserved S. aureus FRI clinical isolates., Methods: Current Procedural Terminology codes were used to identify patients with FRI from January 1, 2021 to December 31, 2021. Preserved S. aureus FRI isolates from the cases were then tested against a library of 51 Staphylococcal bacteriophages from an American company. This was conducted by assessing the ability of bacteriophages to reduce bacterial growth over time. Growth inhibition greater than 16 h was considered adequate for this study., Results: All of the S. aureus preserved clinical isolates had at least one bacteriophage with robust lytic activity and six bacteriophages (11.8 %) had robust lytic activity to seven or more of the clinical isolates. However, 41 of the bacteriophages (80.4 %) had activity to less than three of the clinical isolates and no bacteriophage had activity to all the clinical isolates., Conclusion: Our findings show that Staphylococcal bacteriophage therapeutics are readily available for S. aureus FRI clinical isolates. However, when correlated with the current barriers to using bacteriophages to treat FRI, designated Staphylococcal bacteriophage cocktails with broad spectrum activity should be created., Competing Interests: Declaration of competing interest J. B. Doub was a previous consultant with Adaptive Phage Therapeutics and currently is receiving a grant (13582210) from the National Institutes of Health. J. Fackler is an employee of Adaptive Phage Therapeutics. R. V. O'Toole is a paid consultant for Stryker, receives stock options from Imagen, and receives royalties from Lincotek, all unrelated to this research. The remaining authors report no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Treating recurrent multidrug resistant (MDR) urosepsis in pediatric transplant recipients can be challenging. Particularly when antibiotics fail to prevent future occurrence and the nidus is seemingly undiscoverable. While there is an increasing amount of data on phage therapy, to our knowledge, there are no published cases involving pediatric renal transplant recipients. Therefore, we present a challenging clinical case in which phage therapy was used in a pediatric renal transplant recipient who developed recurrent MDR urosepsis with an unclear source., Case Presentation: Our patient was a 17-year-old female who initially developed urosepsis caused by extended-spectrum β-lactamase (ESBL) Escherichia coli , while being treated with an immunosuppressant regimen because of kidney rejection secondary to poor immunosuppression therapy compliance. She was admitted to our hospital intermittently for 4 months with 4 episodes of urosepsis caused by ESBL E. coli . She received multiple courses of antibiotics (mainly ertapenem) and underwent a fecal material transplant to eradicate her ESBL E. coli colonized gastrointestinal tract. Because of recurrent development of urosepsis after antibiotic treatment, she later underwent treatment with a phage cocktail consisting of 2 isolate-specific phages. After a prolonged antibiotic course and subsequent 3-week intravenous phage treatment, she had no ESBL E. coli in her urinary cultures for 4 years post-treatment., Discussion: This case highlights the challenges of treating recurrent ESBL E. coli infections in a pediatric renal transplant patient and provides evidence that phage therapy may prove useful in such cases., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Given the specificity of bacteriophage attachment receptors, a single bacterial isolate is currently utilized to match to a bacteriophage therapeutic, thereby extrapolating activity to all bacteria in vivo. Consistently, the main bacteriophage attachment receptor for Staphylococcus aureus is teichoic acid, and it is known that this receptor has phenotypic variations in different in vivo environments. Consequently, the aim of this study was to determine whether bacteriophage activity is similar across all in vivo prosthetic joint infection environments., Methods: Three patients with prosthetic joint infections who had S. aureus grow from arthrocentesis cultures and at least three deep tissue cultures were analyzed for growth inhibition with a library of 56 bacteriophages., Results: Discordant bacteriophage activity was seen across the different in vivo environments. Furthermore, bacteriophages with the most robust lytic potential to the arthrocentesis isolates usually did not demonstrate activity corresponding to all the deep tissue clinical isolates., Conclusion: Variations of bacteriophage activity can occur between the different in vivo clinical environments, which is likely secondary to different glycosylation patterns of teichoic acid. Consequently, if discordant activity is present, retreating with bacteriophages that have activity is likely needed for effective, reproducible outcomes., Competing Interests: Conflict of interest J.F. and M. L. are affiliated with APT. The remaining authors report no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Hospitalized patients are at risk of developing serious multidrug resistant bacterial infections. This risk is heightened in patients who are on mechanical ventilation, are immunocompromised, and/or have chronic comorbidities. We report the case of a 52-year-old critically ill patient with a multidrug resistant Acinetobacter baumannii (MDR-A) respiratory infection who was successfully treated with antibiotics and intravenous and nebulized bacteriophage therapy.

Background: Prosthetic joint infection (PJI) is a potentially limb-threatening complication of total knee arthroplasty. Phage therapy is a promising strategy to manage such infections including those involving antibiotic-resistant microbes, and to target microbial biofilms. Experience with phage therapy for infections associated with retained hardware is limited. A 62-year-old diabetic man with a history of right total knee arthroplasty 11 years prior who had suffered multiple episodes of prosthetic knee infection despite numerous surgeries and prolonged courses of antibiotics, with progressive clinical worsening and development of severe allergies to antibiotics, had been offered limb amputation for persistent right prosthetic knee infection due to Klebsiella pneumoniae complex. Intravenous phage therapy was initiated as a limb-salvaging intervention., Methods: The patient received 40 intravenous doses of a single phage (KpJH46Φ2) targeting his bacterial isolate, alongside continued minocycline (which he had been receiving when he developed increasing pain, swelling, and erythema prior to initiation of phage therapy). Serial cytokine and biomarker measurements were performed before, during, and after treatment. The in vitro anti-biofilm activity of KpJH46Φ2, minocycline and the combination thereof was evaluated against a preformed biofilm of the patient's isolate and determined by safranin staining., Results: Phage therapy resulted in resolution of local symptoms and signs of infection and recovery of function. The patient did not experience treatment-related adverse effects and remained asymptomatic 34 weeks after completing treatment while still receiving minocycline. A trend in biofilm biomass reduction was noted 22 hours after exposure to KpJH46Φ2 (P = .063). The addition of phage was associated with a satisfactory outcome in this case of intractable biofilm-associated prosthetic knee infection. Pending further studies to assess its efficacy and safety, phage therapy holds promise for treatment of device-associated infections., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Bacteriophage therapy (BT) uses bacteriophages to treat pathogenic bacteria and is an emerging strategy against multidrug-resistant (MDR) infections. Experience in solid organ transplant is limited. We describe BT in 3 lung transplant recipients (LTR) with life-threatening MDR infections caused by Pseudomonas aeruginosa (n = 2) and Burkholderia dolosa (n = 1). For each patient, lytic bacteriophages were selected against their bacterial isolates. BT was administered for variable durations under emergency Investigational New Drug applications and with patient informed consent. Safety was assessed using clinical/laboratory parameters and observed clinical improvements described, as appropriate. All patients received concurrent antibiotics. Two ventilator-dependent LTR with large airway complications and refractory MDR P. aeruginosa pneumonia received BT. Both responded clinically and were discharged from the hospital off ventilator support. A third patient had recurrent B. dolosa infection following transplant. Following BT initiation, consolidative opacities improved and ventilator weaning was begun. However, infection relapsed on BT and the patient died. No BT-related adverse events were identified in the 3 cases. BT was well tolerated and associated with clinical improvement in LTRs with MDR bacterial infection not responsive to antibiotics alone. BT may be a viable adjunct to antibiotics for patients with MDR infections., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Phage therapy is a promising antibacterial strategy, especially given that drugresistant bacterial infections are escalating worldwide. Because phages are not active against all strains of a given species, phages being considered for therapeutic use would ideally be tested against bacterial isolates from individual patients prior to administration. Standardized, clinically validated phage susceptibility testing (PST) methods are needed for assessing in vitro phage activity. This study compared two high-throughput liquid-based PST assays. The first, using the Biolog Omnilog™, assessed changes in microbial respiration leading to color changes based on a tetrazolium dye. The second, Agilent BioTek Cytation 7, assessed changes in optical density. Both used 96-well microtiter plate formats. A total of 55 diverse phages with activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, or Enterococcus faecalis were studied against their respective susceptible bacterial hosts and non-susceptible controls, with susceptibility defined based on plaque assay. PST was performed by both assays in replicates, with results compared in terms of hold times (time through which bacterial growth is inhibited by phage compared to controls). Coefficients of variance and interclass correlation coefficients were used to assess inter- and intra-assay reproducibility. Based on a ≤50% coefficient of variance cutpoint, 87% of Biolog and 84% of Agilent assays were considered valid for susceptible bacteria, with 100% considered valid for non-susceptible bacteria by both systems. Using a 8 h hold time cutpoint, 100% of the results matched between the two assays. The interclass correlation coefficient showed 26% excellent agreement, 35% good agreement, and 17% moderate agreement between the two assays for susceptible isolates and 100% excellent agreement for non-susceptible isolates. Overall, the assays compared provided good/fair statistical reproducibility for the assessment of phage susceptibility. [ABSTRACT FROM AUTHOR]

A patient with a trauma-related left tibial infection associated with extensively drug-resistant Acinetobacter baumannii and multidrug-resistant Klebsiella pneumoniae was treated with bacteriophages and antibiotics. There was rapid tissue healing and positive culture eradication. As a result, the patient's leg did not have to be amputated and he is undergoing rehabilitation. [ABSTRACT FROM AUTHOR]