Abstract

Background: 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. Methods: 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. Findings: 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. Conclusions: 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. 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.

Original languageEnglish
Pages (from-to)600-611.e4
JournalMed
Volume4
Issue number9
DOIs
StatePublished - 8 Sep 2023

Funding

FundersFunder number
Royal Australasian College of Physicians for a Cottrell Research
National Institutes of Health
National Institute of Arthritis and Musculoskeletal and Skin DiseasesR01 AR082167
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Rosetrees TrustA2232
Rosetrees Trust
National Health and Medical Research CouncilAPP2002520
National Health and Medical Research Council
United States-Israel Binational Science Foundation2017123
United States-Israel Binational Science Foundation
Israel Science Foundation442/18, ISF_1349/20
Israel Science Foundation
Ministry of Science and Technology, Israel88555
Ministry of Science and Technology, Israel

    Keywords

    • Pseudomonas aeruginosa
    • Translation to patients
    • bacteriophage therapy
    • bone and joint infections
    • clinical phage microbiology
    • persistant infections
    • phage therapy
    • resistant infections

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