Phage therapy makes a comeback to counteract multidrug resistance

Infectious diseases

By Mardi Chapman

29 May 2018

Dr Thomas Patterson’s wife was told to expect the worst after he contracted a multidrug resistant Acinebacter baumannii infection in Egypt in 2015.

Despite being flown to Germany for treatment and eventually home to the US, he had developed an uncontrolled intra-abdominal infection that put him in a coma for three months in ICU.

Dr Patterson recovered. But not everyone’s wife is an infectious diseases epidemiologist equipped for research and with colleagues prepared to go the extra mile.

Speaking in the ATS 2018 Keynote Series, Dr Stephanie Strathdee and one of her medical colleagues Professor Robert Schooley presented both the case study and a call for more research into phage therapy.

Dr Schooley, an infectious diseases physician at the University of California San Diego, told the meeting clinicians were often blamed for antimicrobial resistance although they were not the only contributors.

Nevertheless, they were on the frontline.

“We need to persist with antibiotic stewardship in the fight against multidrug resistance but also be prepared to look at novel alternatives.”

He said bacteriophages, marketed in the US during the 1920s and 1930s, were largely abandoned with the advent of antibiotics and evidence-based medicine.

However phages may be making a timely come back in the face of multidrug resistant ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and other organisms of particular interest to respiratory physicians such as Burkholderia cepacia and Mycobacterium species including M. abscessus.

In the US, Acinebacter baumannii has become a remerging a problem for military veterans returning from the Middle East.

Dr Schooley said one the main characteristics of phages was they were extremely specific for particular bacteria, compared to antibiotics which can be broad spectrum.

The treatment for Dr Patterson involved collaboration between myriad researchers with an interest in phage therapy – including the US Navy – and screening a library of phages to find those that might be effective against his pathogen.

Because phages only kill a subset of the bacteria within their target species, two cocktails each containing four phages were used.

Under a FDA single patient approval for emergency use of an investigational new drug, the cocktails were administered both intra-abdominally and intravenously.

In Dr Patterson’s case there was a good outcome from phage therapy. Watch Dr Stephanie Strathdee’s TEDx Talk about their personal phage experience here.

The future of phage therapy

Dr Schooley said he has since treated five patients with phage therapy including P. aeruginosa infections both pre- and post-lung transplant.

While there are now increasing numbers of case reports, he said there needs to be a move towards rigorous clinical trials.

Comparisons between the limited number of commercially available phages and the customised phage cocktail approach were necessary.

He said bacteria become resistant to the phages but at the same time capsule changes make the pathogen less invasive. So there may be some synergy with the concomitant use of antibiotics such as minocycline.

He said IV administration appears to work so phages can move to the site of infection, however more needed to be understood about their role in localised versus disseminated infections.

“We also need to understand their pharmacokinetics and pharmacodynamics, resistance kinetics, any other indirect antimicrobial properties, and how to optimise their valency.”

He said as well as the lytic cycle of phages, when they inject their DNA into and destroy bacteria, some also had a lysogenic cycle, when they became integrated into but did not destroy their host.

Yet another challenge therefore is to find phages without the lysogenic cycle or to engineer lytic-only versions.

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