[Jerusalem, Israel] – A new international study conducted by the Israeli Phage Therapy Center (IPTC) led by Prof. Ran Nir-Paz at Hadassah Hebrew University Medical Center and Prof. Ronen Hazan of the Faculty of Dental Medicine at The Hebrew Universityof Jerusalem, using phage PASA16 on compassionate basis to treat tough Pseudomonas aeruginosa infections, has shown promising results with an 86.6% success rate. This research involving 16 patients with persistent infections represents the largest of its kind and brings encouraging findings. The study’s success demonstrates the potential effectiveness of PASA16 phage therapy in tackling challenging Pseudomonas aeruginosa infections, paving the way for future clinical trials and encouraging further exploration of phage therapy as an alternative and auxiliary approach against antibiotic-resistant infections.
Phage therapy, the use of specific anti-bacterial viruses against infections, has garnered attention as a critical addition to conventional antibiotics, though clinical trials in this area have been limited. However, recent compassionate phage therapy cases have shown potential, albeit with scarce evidence on treating difficult infections. This study sheds light on the potential role of phages in combination with antibiotics in combating the hard-to-treat pathogen Pseudomonas aeruginosa infections that were unresponsive to conventional treatments.
Prior to treatment, all Pseudomonas aeruginosa isolates from patients were tested and treatment was personalized provided to those who were found to be sensitive to the PASA16 phage. During the PASA16 phage treatment, only minor side effects were observed, which were manageable. Remarkably, 13 out of 15 patients with available data achieved a favorable clinical outcome, resulting in an impressive 86.6% success rate. This highlights the potential of combining PASA16 phage with antibiotics as a promising approach for patients with previously unsuccessful treatments. The duration of treatment spanned from 8 days to 6 weeks (majority of ~ 2 weeks), with one- to twice-daily regimens, offering a time-efficient option.
visualization of the phage pasa16. credit: ronen hazan.
In conclusion, this compassionate use case series demonstrates the potential effectiveness of
PASA16 phage therapy in tackling tough Pseudomonas aeruginosa infections. By outlining potential clinical protocols, this study paves the way for future trials. The success observed encourages further research and exploration of phage therapy as an alternative and complementary approach to combat antibiotic-resistant infections.
Prof. Ran Nir-Paz, co- lead researcher of the study at IPTC of Hadassah Hebrew University Medical Center, expressed excitement about the findings, stating, “We are elated by the promising results of our study using phage PASA16 to treat tough Pseudomonas aeruginosa infections. This groundbreaking research offers hope for patients with persistent infections and highlights the potential of phage therapy as a valuable alternative to conventional antibiotics in combating antibiotic-resistant pathogens.”
Prof. Ronen Hazan the co-lead researcher of the IPTC, also the head of the Bio-research institute of the Faculty of Dental Medicine at The Hebrew University of Jerusalem stated: “We are encouraged by the findings! The study’s 86.6% success rate offers hope for patients with persistent infections and underscores the potential of phage therapy as an alternative to combat antibiotic-resistant pathogens.”
Pseudomonas aeruginosa is a type of bacteria commonly found in the environment, such as soil, water, and plants, and as part of bacteria residing in humans. It is both a pathogen and opportunistic bacteria, causing infections in individuals with weakened immune systems or underlying health conditions. Known for its potentially complicated and life-threatening infections, Pseudomonas aeruginosa poses challenges in healthcare settings.
These infections can range from mild to severe, affecting various body parts, including the lungs, urinary tract, skin, and wounds. It is a common cause of hospital-acquired infections, particularly in immunocompromised patients or those using mechanical ventilation or invasive devices. The bacteria’s ability to form protective biofilms hinders treatment, sometimes necessitating the combination of antibiotics and alternative therapies like phage therapy. Strict infection control measures in healthcare facilities are essential to combat its persistence.
The study compiled comprehensive clinical data on 15 out of 16 patients treated with phage PASA16, assessing its efficacy in treating the infections. The phage, provided pro bono by the American phage company “Adaptive Phage Therapeutics”, was administered through various methods, including intravenous, local application to the infection site, and topical use. The data mainly covered patients with osteoarticular and foreign-device-associated infections.
As the fight against antibiotic resistance continues, this compassionate use case series represents a significant step forward in exploring phage therapy as a potential solution for patients with tough Pseudomonas aeruginosa infections.
Phage therapy has re-emerged as a potential solution for antimicrobial-resistant and non-resolving infections, as phages specifically target other microorganisms. While compassionate use cases for phage therapy have been implemented, clinical trials remain limited. 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 the susceptibility of their infective agent to both the phage alone and in combination with antibiotics. The study findings demonstrate a favorable outcome in over 80% of treated patients, with minimal side effects. Based on these findings, further compassionate use cases and the development of clinical trial protocols should follow.
For more information about the study, please refer to the article: “Refractory Pseudomonas aeruginosa infections treated with phage PASA16: A compassionate use case series” published at MED https://doi.org/10.1016/j.medj.2023.07.002
Funding: 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.
Research Team: Hadil Onallah,1,2 Ronen Hazan,2,4 Ran Nir-Paz,1,2,3,32,* PASA16 study group, Michael J. Brownstein,5 Joseph R. Fackler,5 Bri’Anna Horne,5 Robert Hopkins,5 Subhendu Basu,5 Ortal Yerushalmy,2,4 Sivan Alkalay-Oren,2,4 Ron Braunstein,2,4 Amit Rimon,2,4 Daniel Gelman,2,4,6 Leron Khalifa,2,4 Karen Adler,2,4 Mohanad Abdalrhman,2,3 Shira Gelman,2,4,6 Eyal Katvan,7,8 Shunit Coppenhagen-Glazer,2,4 Allon Moses,3 Yonatan Oster,1,3 Michal Dekel,9 Ronen Ben-Ami,9 Amal Khoury,9 Daniel J. Kedar,10 Suzy E. Meijer,10 Itay Ashkenazi,11 Nancy Bishouty,12 Dafna Yahav,13,31 Eran Shostak,14 Gilat Livni,15 Mical Paul,16 Menachem Gross,17 Matityahou Ormianer,17 Saima Aslam,18,19 Michele Ritter,18 Kenneth L. Urish,20 Ricardo M. La Hoz,21 Ameneh Khatami,22,23 Philip N. Britton,22,23 Ruby C.Y. Lin,24 Jonathan R. Iredell,23,24 Aleksandra Petrovic-Fabijan,24 Stephanie Lynch,24 Pranita D. Tamma,25 Alexandra Yamshchikov,26,27 Emil Lesho,26 Megan Morales,28 Alissa Werzen,29 and Kapil Saharia30
Institutions: 1-Faculty of Medicine, Hebrew University of Jerusalem; 2-The Israeli Phage Therapy Center (IPTC) of Hadassah Medical Center and the Hebrew University; 3-Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center (HHUMC); 4-Institute of Biomedical and Oral Research (IBOR), Faculty of Dental Medicine, The Hebrew University of Jerusalem; 5-Adaptive Phage Therapeutics, Gaithersburg, USA; 6-Department of Military Medicine, Faculty of Medicine, The Hebrew University of Jerusalem; 7-The Martin (Szusz) Department of Land of Israel Studies and Archaeology, Bar Ilan University; 8-Peres Academic Center, Rehovot; 9-Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University; 10-Department of Plastic and Reconstructive Surgery, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University; 11-Division of Orthopedic Surgery, Tel Aviv Sourasky Medical Center; 12-Pharmacy Department, Tel Aviv Sourasky Medical Center; 13-Infectious Disease Unit, Rabin Medical Center; 14-Pediatric Cardiac Intensive Care Unit, Schneider Children’s Medical Center; 15-Pediatric Infectious Diseases Unit, Schneider Children’s Medical Center; 16-Rambam Health Care Campus and Faculty of Medicine, The Technion – Israel Institute of Technology; 17-Department of Otolaryngology-Head and Neck Surgery, Hadassah-Hebrew University Medical Center; 18-Division of Infectious Diseases and Global Public Health, University of California; 19-Center for Innovative Phage Applications and Therapeutics, University of California; 20-Bone and Joint Center, Magee Hospital, Department of Orthopedic Surgery, University of Pittsburgh School of Medicine; 21-Division of Infectious Disease and Geographic Medicine, University of Texas Southwestern Medical Center; 22-Department of Infectious Diseases and Microbiology, The Children’s Hospital at Westmead, Australia.
The Hebrew University of Jerusalem is Israel’s premier academic and research institution. With over 25,000 students from 90 countries, it is a hub for advancing scientific knowledge and holds a significant role in Israel’s civilian scientific research output, accounting for nearly 40% of it and has registered over 11,000 patents. The university’s faculty and alumni have earned eight Nobel Prizes and a Fields Medal, underscoring their contributions to ground-breaking discoveries. In the global arena, the Hebrew University ranks 77th according to the Shanghai Ranking, making it the top-ranked Israeli institution. To learn more about the university’s academic programs, research initiatives, and achievements, visit the official website at http://new.huji.ac.il/en
About The Hadassah Medical Center
The Hadassah Medical Center was established in 1912 and is a world-class facility. For more than a century, Hadassah has set the standard of excellence for medical care and research in Israel. Every year, Hadassah provides nearly one million people with hospital services, and in keeping with worldwide trends, the Hadassah University Medical Center in Israel is moving toward day care and day hospitalization to reduce costs and risk of infection. Our doctors and scientists are on the frontlines, uniquely positioned to pinpoint ever-evolving medical needs. Their experience and ingenuity have yielded new ideas with huge potential in all areas of medicine, including therapeutics, diagnostic medical devices, and digital health. For more information about the Hadassah Medical Center, please visit https://www.hadassah.org.il/en/
About The Israeli Phage Therapy Center (IPTC)
The IPTC is one of the leading phage therapy centers in the world, operating since 2018 by the Hadassah Medical Center and the Hebrew University of Jerusalem. The center has received more than 200 requests for compassionate use of phage therapy for previously failed infections from Israel, the US, Australia, Finland, Germany and other countries. The most common indications for phage requests were bone and respiratory infections, with the most common bacteria being Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus.