Lessons Learned From the First 10 Consecutive Cases of Intravenous Bacteriophage Therapy to Treat Multidrug-Resistant Bacterial Infections at a Single Center in the United States

Abstract

Background Due to increasing multidrug-resistant (MDR) infections, there is an interest in assessing the use of bacteriophage therapy (BT) as an antibiotic alternative. After the first successful case of intravenous BT to treat a systemic MDR infection at our institution in 2017, the Center for Innovative Phage Applications and Therapeutics (IPATH) was created at the University of California, San Diego, in June 2018. Methods We reviewed IPATH consult requests from June 1, 2018, to April 30, 2020, and reviewed the regulatory process of initiating BT on a compassionate basis in the United States. We also reviewed outcomes of the first 10 cases at our center treated with intravenous BT (from April 1, 2017, onwards). Results Among 785 BT requests to IPATH, BT was administered to 17 of 119 patients in whom it was recommended. One-third of requests were for Pseudomonas aeruginosa, Staphylococcus aureus, and Mycobacterium abscessus. Intravenous BT was safe with a successful outcome in 7/10 antibiotic-recalcitrant infections at our center (6 were before IPATH). BT may be safely self-administered by outpatients, used for infection suppression/prophylaxis, and combined successfully with antibiotics despite antibiotic resistance, and phage resistance may be overcome with new phage(s). Failure occurred in 2 cases despite in vitro phage susceptibility. Conclusions We demonstrate the safety and feasibility of intravenous BT for a variety of infections and discuss practical considerations that will be critical for informing future clinical trials.

Considerations for Phage Therapy Against Mycobacterium abscessus

“…A recent report about requests for phage therapy at the Center for Innovative Phage Applications and Therapeutics (IPATH) in the United States shows that from June 1, 2018, to April 30, 2020, there have been 90 outcomes of requests for phage therapy against mycobacteria (47 M. abscessus , 23 M. avium , seven Mycobacterium chimera , seven M. species, two Mycobacterium chelonae , and one M. smegmatis , Mycobacterium xenopi , Mycobacterium bolletii , and Mycobacterium genavense ). In a summarizing table, they point that nine lytic phages were found against the isolates of M. abscessus and the phage therapy was administered to four patients with a median time from request to administration of 176 days, however, no more information is given about these treatments ( Aslam et al, 2020 ).…”

A Phage Therapy Guide for Clinicians and Basic Scientists: Background and Highlighting Applications for Developing Countries

“…Recently, there has been a noticeable increase in compassionate use of phage therapy to treat serious bacterial infections and the results are promising ( Maddocks et al, 2019 ; Aslam et al, 2020 ; Cano et al, 2020 ; Petrovic Fabijan et al, 2020b ). However, robust clinical trials are very few and mostly unsuccessful ( Sarker et al, 2016 ; Jault et al, 2019 ; Leitner et al, 2020 ).…”

Bacteriophage Therapy of Bacterial Infections: The Rediscovered Frontier

“…The patient with recurrent B. dolosa infection did not respond to bacteriophage therapy. The safety and feasibility of phage treatment of patients with various infections at a single center in the U.S. was established, although two of the 10 patients described did not respond to therapy [95].…”