Phage Therapy May Help Resolve Multidrug-resistant Pseudomonas Airway Infections, Case Report Suggests

Phage Therapy May Help Resolve Multidrug-resistant Pseudomonas Airway Infections, Case Report Suggests

Armata Pharmaceuticals‘ investigational phage therapy AP-PA01 combined with antibiotics holds promise for treating multidrug-resistant Pseudomonas airway infections, updated data from a case study show.

A young woman with cystic fibrosis (CF) was successfully treated for a multidrug-resistant Pseudomonas aeruginosa pneumonia using AP-PA01 and antibiotics. At 100 days after the treatment, the woman remained free of pneumonia or CF flares.

The case report was described in the study “Successful adjunctive use of bacteriophage therapy for treatment of multidrug‑resistant Pseudomonas aeruginosa infection in a cystic fibrosis patient,” published in the journal Infection.

There is growing evidence that bacteriophages — viruses that specifically infect and kill bacteria — may be a promising option to fight bacterial infections, particularly those with multiple antibiotic resistance which are difficult to treat.

“Patients suffering from cystic fibrosis are particularly vulnerable to Pseudomonas aeruginosa infections, and repeated exposure to antibiotics puts them at high risk for developing multidrug resistant strains,” Saima Aslam, MD, professor at the University of California, San Diego, and principal investigator of the study said in a press release.

The report describes the case of a 26-year-old woman with CF who developed multidrug-resistant Pseudomonas aeruginosa pneumonia that persisted despite treatment with multiple antibiotics.

The patient was waiting for a lung transplant when she was admitted with a pulmonary exacerbation leading to respiratory failure that required mechanical ventilation.

She was diagnosed with pneumonia caused by two different multidrug-resistant strains of P. aeruginosa — a non-mucus-producing strain, sensitive to the antibiotic colistin (brand name Coly-Mycin and others), and a mucus-producing strain sensitive to meropenem (brand name Merrem and others) and piperacillin–tazobactam (brand name Zosyn and others).

The patient was treated with several antibiotics without success, and got worse over time: her fever returned, sputum production increased, as did her oxygen requirements. Accompanying her progressive respiratory decline, she also developed kidney failure as an adverse effect from one of the antibiotics.

At this point, the U.S. Food and Drug Administration approved an emergency Investigational New Drug (IND) application filled by doctors to get expanded access to AP-PA01. This product combined four types of bacteriophages, and was produced by AmpliPhi Biosciences — which merged with C3J Therapeutics at the beginning of 2019 to create Armata.

The patient was given intravenous injections of AP-PA01, administered every six hours, over eight weeks. Throughout the course of the therapy, she remained on the antibiotics azythromycin and piperacillin–tazobactam, and in the first three weeks, she also received ciprofloxacin (brand name Cipro and others).

At day seven, the patient no longer had fever, but had a dry cough with difficulty in expectorating sputum. Over time, her pneumonia resolved, and she transitioned to a lower flow rate of oxygen.

At week eight, the patient was no longer coughing up sputum, and could walk independently. Her acute kidney injury resolved, and white blood cell counts returned to normal. No other P. aeruginosa pneumonia or CF exacerbation occurred within 100 days following the end of the phage course. She underwent a successful lung transplant nine months later.

“Only after phage therapy was introduced as an adjunct to antibiotic treatment did the infection resolve, and the patient went on to receive a bilateral lung transplant,” Aslam said. “This successful outcome speaks to the great potential of phage-based therapeutics to address the growing threat of antibiotic resistance and provides very strong rationale for continued development.”

Several airway samples of P. aeruginosa were taken throughout the woman’s treatment to check for sensitivity to the therapy. Consistent with the patient’s response, bacteria remained mostly sensitive to AP-PA01, from the beginning until the end of the treatment, except for a transient nonsensitive isolate identified on the ninth day.

No adverse events related to AP-PA01 were noted, in terms of clinical signs or laboratory tests, demonstrating “that intravenous BT [bacteriophage therapy] is safe and well tolerated and can be used as an adjunct to antibiotics,” the researchers wrote.

“The publication of this successful treatment case study, with an Armata phage administered through our single-patient expanded access program, adds to the impressive and growing body of evidence demonstrating the effectiveness of our phage product candidates, and bacteriophage in general,” Todd R. Patrick, CEO of Armata, said in a press release.

He emphasized that the expanded access program has been very helpful to demonstrate the potential of phage therapy but that “compassionate use cases limits our ability to focus our resources on formal clinical trials required for FDA approval.”

As such, he said, “we plan to end our single-patient expanded access program and instead focus on demonstrating phage efficacy through well-powered clinical trials.”

Armata’s pipeline is currently focused on the development of natural and synthetic (lab-made) bacteriophages to target two potentially life-threatening bacteria — Staphylococcus aureus and Pseudomonas aeruginosa — including multidrug-resistant strains.

The company expects to submit an IND later this year for a phage therapy targeting Staphylococcus aureus —  a common cause of multidrug-resistant and deadly infections.

In addition to its work on AP-PA01, Armata is also engineering the natural P. aeruginosa phage to create a novel synthetic phage product, AP-PA02.

Another synthetic phage is being developed in collaboration with Merck, but its target remains undisclosed.

Ana Pena, PhD Author
Ana is a molecular biologist enthusiastic about innovation and communication. In her role as a science writer she wishes to bring the advances in medical science and technology closer to the public, particularly to those most in need of them. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she focused her research on molecular biology, epigenetics and infectious diseases.
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Ana Pena, PhD Author
Ana is a molecular biologist enthusiastic about innovation and communication. In her role as a science writer she wishes to bring the advances in medical science and technology closer to the public, particularly to those most in need of them. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she focused her research on molecular biology, epigenetics and infectious diseases.
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