Introduction: Bacteriophage therapy is emerging as an approach to highly resistant and severe infection. Randomised studies are lacking but there have been some high-profile examples of successful salvage therapy using phages for highly antibiotic-resistant infection in critically ill patients. Here we describe the likely place of these agents in the pharmacopoiea and outline our world-first experience of treating fifteen critically ill patients with adjunctive GMP-quality bacteriophage cocktail, including for endocarditis and septic shock.
Objectives/Aims: The aim of our study was to assess safety and tolerability of adjunctive bacteriophage therapy in patients with severe Staphylococcus aureus and Pseudomonas aeruginosa infections, with particular attention to practical aspects of bacteriophage delivery in the intensive care unit (ICU) including compatibility, toxicity and safety for patients and staff.
Methods: In conjunction with the patient’s prescribed antibiotics regime, 14 consented patients with S. aureus sepsis, including infective endocarditis (n=8) were treated for 14 days with AB-SA01 (AmpliPhi Biosciences) based on a locally-approved protocol (registered under Therapeutic Goods Administration and Clinical Trial Notification). There was also one case of nebulised and intravenous antipseudomonal therapy. Physiological, haematological and biochemical markers, and mortality at day 28 and day 90 were measured.
Results: Seven of thirteen (54%) patients survived past day 28, six of seven patients (86%) survived past day 90 and one patient was not susceptible to AB-SA01 and was excluded from iTT analysis. During therapy, we observed reduction in inflammatory markers, no adverse events and no evidence of phages were found on environmental swabs. We used correct personal protective equipment including P2/N95 fluid resistant masks during nebulisation of phages.
Conclusion: We demonstrated for the first time that phage therapy produced under GMP conditions is safe and well-tolerated in critically ill patients. Our practical experience highlighted it is safe for healthcare professionals to administer this therapy.
© 2020 Published by Elsevier Inc.