Stewardship / Resistance Scan for Jan 19, 2022

Phage therapy for fracture-related infection
;
New rapid diagnostic test

Paper highlights use of pre-adapted phage against a pan-resistant infection

A new paper in Nature Communications describes the use of a pre-adapted bacteriophage in combination with antibiotics to treat a patient with a fracture-related, pandrug-resistant (PDR) Klebsiella pneumoniae infection.

The case involved a 30-year-old woman who suffered traumatic wounds, including a broken femur, and underwent several surgeries after a bombing at the Brussels airport in 2016. More than 5 months after admission to the hospital, surgical biopsies from the femur showed two strains of K pneumoniae, one of which was extensively drug-resistant. Long-term antibiotic treatment failed to cure the fracture-related infection (FRI), and clinicians then began considering phage therapy.

The phage found to have the highest activity against the patient's K pneumoniae isolates had been isolated from sewage water in Tblisi, Georgia, in 2012. To enhance the lytic activity of the phage against the isolates, a phage adaptation procedure was applied, and the adapted phage was then propagated.

Due to a lack of consensus among the treating physicians, use of the pre-adapted phage didn't begin until more than 700 days post-injury, at which point the K pneumoniae infection had become PDR. But the phage was still active against the isolates, and following bone graft surgery, physicians began 6 days of phage therapy in conjunction with meropenem and colistin, followed by ceftazidime/avibactam. The patient began to see progress 2 days into the combination therapy, and after 3 months, the FRI was controlled.

Subsequent bone and wound cultures showed no signs of persistent or recurrent infection. Three years after the treatment was initiated, the patient has regained mobility.

The authors of the paper say the case illustrates the complexity of managing FRIs caused by multidrug-resistant bacteria and the need for new antimicrobial agents, but it also reveals new strategies for the use of phage therapy.

"Pre-adapted phage-antibiotic combination therapy ultimately led to a positive clinical outcome of a long-standing PDR K. pneumoniae FRI," they wrote. "The present case study can open a new way of thinking about phage therapy: the use of individually adjusted phage-antibiotic combinations."
Jan 18 Nat Commun paper

 

Rapid diagnostic receives Breakthrough Device Designation from FDA

California-based diagnostics company Pathogenomix Inc. today announced that the US Food and Drug Administration (FDA) has granted it a Breakthrough Device Designation for Patho-Seq, an assay designed to rapidly detect hundreds of clinically relevant bacteria from patient infections.

According to a company press release, Patho-Seq uses next-generation sequencing technology to return results 48 hours faster than the currently approved standard-of-care tests, and can identify multiple bacterial species from a single test run in cases where more than one pathogen may be contributing to a patient's infection. The test was granted Breakthrough Device Designation for the identification of infectious bacteria from sepsis and bacteremia, bacterial meningitis, joint and implant infections, and tick-borne bacterial infections.

Pathogenomix collaborated with Mayo Clinic on the development of the techniques and data that supported the FDA application.

Through the Breakthrough Device Program, the FDA will provide Pathogenomix with continued guidance and accelerated review for premarket approval and de novo marketing authorization.
Jan 19 Pathogenomix press release

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