Refractory Pseudomonas aeruginosa infections treated with phage PASA16: A compassionate use case series

• Published in: Med (New York, N.Y. : Online) Vol. 4; no. 9; pp. 600 - 611.e4
• Main Authors: Onallah, Hadil, Hazan, Ronen, Nir-Paz, Ran, Brownstein, Michael J., Fackler, Joseph R., Horne, Bri’Anna, Hopkins, Robert, Basu, Subhendu, Yerushalmy, Ortal, Alkalay-Oren, Sivan, Braunstein, Ron, Rimon, Amit, Gelman, Daniel, Khalifa, Leron, Adler, Karen, Abdalrhman, Mohanad, Gelman, Shira, Katvan, Eyal, Coppenhagen-Glazer, Shunit, Moses, Allon, Oster, Yonatan, Dekel, Michal, Ben-Ami, Ronen, Khoury, Amal, Kedar, Daniel J., Meijer, Suzy E., Ashkenazi, Itay, Bishouty, Nancy, Yahav, Dafna, Shostak, Eran, Livni, Gilat, Paul, Mical, Gross, Menachem, Ormianer, Matityahou, Aslam, Saima, Ritter, Michele, Urish, Kenneth L., La Hoz, Ricardo M., Khatami, Ameneh, Britton, Philip N., Lin, Ruby C.Y., Iredell, Jonathan R., Petrovic-Fabijan, Aleksandra, Lynch, Stephanie, Tamma, Pranita D., Yamshchikov, Alexandra, Lesho, Emil, Morales, Megan, Werzen, Alissa, Saharia, Kapil
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.09.2023
• Subjects: bacteriophage therapy; bone and joint infections; clinical phage microbiology; persistant infections; phage therapy; Pseudomonas aeruginosa; resistant infections; clinical phage microbiology; persistant infections; resistant infections; phage therapy; Pseudomonas aeruginosa; bacteriophage therapy; Translation to patients; bone and joint infections
• ISSN: 2666-6340; 2666-6340
• DOI: 10.1016/j.medj.2023.07.002

A growing number of compassionate phage therapy cases were reported in the last decade, with a limited number of clinical trials conducted and few unsuccessful clinical trials reported. There is only a little evidence on the role of phages in refractory infections. Our objective here was to present the largest compassionate-use single-organism/phage case series in 16 patients with non-resolving Pseudomonas aeruginosa infections. We summarized clinical phage microbiology susceptibility data, administration protocol, clinical data, and outcomes of all cases treated with PASA16 phage. In all intravenous phage administrations, PASA16 phage was manufactured and provided pro bono by Adaptive Phage Therapeutics. PASA16 was administered intravenously, locally to infection site, or by topical use to 16 patients, with data available for 15 patients, mainly with osteoarticular and foreign-device-associated infections. A few minor side effects were noted, including elevated liver function enzymes and a transient reduction in white blood cell count. Good clinical outcome was documented in 13 out of 15 patients (86.6%). Two clinical failures were reported. The minimum therapy duration was 8 days with a once- to twice-daily regimen. PASA16 with antibiotics was found to be relatively successful in patients for whom traditional treatment approaches have failed previously. Such pre-phase-1 cohorts can outline potential clinical protocols and facilitate the design of future trials. The study was funded in part by The Israeli Science Foundation IPMP (ISF_1349/20), Rosetrees Trust (A2232), United States-Israel Binational Science Foundation (2017123), and the Milgrom Family Support Program. [Display omitted] •A global Pseudomonas aeruginosa infection series that failed conventional treatment•All were compassionate use treated using a single anti-pseudomonal phage, PASA16•For all treatments, Pseudomonas phage susceptibility was demonstrated in the lab•PASA16 phage therapy demonstrated promising outcomes with minimal side effects Phage therapy has re-emerged in the last few years as a potential solution for antimicrobial-resistant and non-resolving infections. While phages are being used on compassionate use bases, clinical trials for phage therapy are still lacking. This study reports the largest case series of consecutive patients with severe Pseudomonas aeruginosa infections who received compassionate use treatment using a single specific phage, PASA16. All 16 patients were treated after demonstrating that their infective agent was susceptible to both the phage alone and in combination with antibiotics. The study findings demonstrate a favorable outcome in >80% of treated patients, with minimal side effects. Based on these findings, further compassionate use cases and clinical trial protocols could follow. Resistant and persistent infections pose a major challenge in modern medicine. Onallah et al. report the largest case series of PASA16 phage compassionate use for the treatment of refractory severe P. aeruginosa infections. Study findings suggest that the use of PASA16 phage and antibiotics may lead to favorable outcomes.