Bacteriophage therapy
rate of an antibiotic-resistant A. baumannii infection was more than 50%. 43 It was not until a bold suggestion of attempting phage therapy p roposed by Patterson’s wife, Stephanie Strathdee, did the spark of hope rekindle. With the help of Dr Ry Young at Texas A&M University, phage experts from all over the world were contacted (Switzerland, Belgium, Poland, Georgia, and India; the Belgian researchers even offered for their phages to be sent in a diplomatic bag). Based on the international effort, a phage cocktail was soon prepared, and the unprecedented experimental treatment was approved by the United States Food and Drug Administration (FDA) on compassionate grounds. 44 The first phage cocktail was directly injected via IV administration into Patterson’s abdomen in synergy with antibiotics. After three days, he woke up from his previous coma, and his situation began to improve. Phage resistance to the initial cocktail emerged after two weeks, and a second phage cocktail developed in a US Navy medical centre was given to overcome the bacterial resistance. 45 It was also observed during Patterson’s phage therapy treatment that phage -resistant bacteria were often re- sensitized to antibiotics, 46 approving the study reported by Chaudhry et al. (2017). Patterson was discharged in August 2016. This unprecedented and successful case of IV phage therapy sparked a new wave of interest in personalized phage therapy across the United States and the world. As a significant milestone of phage therapy in the w estern world, Patterson’s case was presented at the Pasteur Inst itute in Paris at the 100 th -anniversary event of the discovery of the bacteriophage in 1917. 47 The case of Isabelle Carnell-Holdaway, a 15-year-old CF patient from England with double lung transplants who contracted a chronic antibiotic-resistant M. abscessus infection after the transplantation, was one of the successful cases of traditional phage therapy that occurred directly because of Patterson’s success . 48 In Carnell- Holdaway’s case, a three -phage cocktail of three genomically distinct phages was administered via IV administration. The phage research team used the Bacteriophage Recombineering of Electroporated DNA (BRED) technique developed in Dr Graham Hatfull’s (a phage researcher from the University of Pittsburgh, Pennsylvania, USA; a member of the phage research team) lab in 2009, whereby the team managed to extend the host range of one phage isolate (BPs, Fig. 2) and convert another (ZoeJ, Fig. 2) from temperate to virulent. 49 Other than mild symptoms (sweating and flushing), the IV phage treatment was well tolerated throughout by the patient with no significant side effects. Carnell-Holdaway was discharged nine days after the beginning of the treatment. 50 More notably, it was the first successful therapeutic use of engineered phages, marking as an exceedingly historic milestone in the history of phage therapy. Nowadays, it is even possible to sequence a phage, assemble its genome and analyse the results just in a few days in the laboratory. 51
43 Lipman 2019. 44 Schmidt 2019a; Strathdee 2017. 45 Schooley et al. 2017. 46 Schmidt 2019a. 47 Lipman 2019. 48 Phage therapy treats patient with drug-resistant bacterial infection 2019. 49 Dedrick et al. 2019; Schmidt 2019a. 50 Dedrick et al. 2019. 51 Astudillo Skliarova 2021; Schmidt 2019a.
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