A Case Series of Emergency Investigational New Drug Applications for Bacteriophages Treating Recalcitrant Multi-drug Resistant Bacterial Infections: Confirmed Safety and a Signal of Efficacy

The advent and increasing prevalence of antimicrobial resistance commensurate with the absence of novel antibiotics on the horizon raises the spectre of untreatable infections. We must now grapple with infections stemming from extensively multi- and pan-drug resistant bacterial strains. Potential non-antibiotic options to treat Multi-Drug Resistant (MDR) infections include bacteriophages and there has been much fervour in resurrecting research into its clinical use.

Although not subjected to the contemporary rigorous scientific standards for clinical trials, there appears to be an abundance of data purporting safety of bacteriophage therapy regardless of administration route. The US Navy and Adaptive Phage Therapeutics have taken a precision approach to development of bacteriophage therapy. Herein, as opposed to fixed phage cocktails, we exploit the quintessential example of personalized medicine by acquiring the patient’s infecting isolate and identifying a phage cocktail proven to lyse the bacteria. As we prepare to execute our FDA regulated clinical phase II bacteriophage therapeutic trials in the ensuing year(s), we have engaged in numerous compassionate use eIND cases to provide potentially life-saving bacteriophage treatment to patients either failing conventional antibiotic therapy due to MDR resistance, or stemming from an inability to secure definitive source control. In all eIND cases, “personalized” bacteriophage cocktails were selected which “targeted” the infecting organism. This case series reports upon 13 emergencies investigational new drug (eIND) cases whereby patients failing antibiotic therapy safely received bacteriophage mixtures (cocktails) without identifying any bacteriophagemediated adverse effects. Adjudicated microbiologic eradication of the targeted bacterial isolate was achieved in 11 cases, while 6 cases were clinically adjudicated to have achieved therapeutic efficacy defined as clinical resolution. The balance of non-resolved cases was secondary to curtailed therapy (patient expiring), noninfectious mediated organ failure, or relapse of infection from biofilm-mediated infections.

Author(s):

Christopher A Duplessis, Michael Stockelman, Theron Hamilton, Greg Merril, Michael Brownstein, Kimberly Bishop-lilly, Robert Schooley, Matthew Henry, Bri’Anna Horne, Brittany M. Sisson, Javier Quinones, Saima Aslam, S Lavergne, Ran Nir-Paz, and Biswajit Biswas

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