Stewardship / Resistance Scan for Jan 19, 2022

News brief

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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News Scan for Jan 19, 2022

News brief

Study finds no evidence of live virus in breast milk of moms with COVID-19

A small University of California study finds no evidence that breast milk from mothers infected with SARS-CoV-2 transmits the virus to their babies.

The study, published today in Pediatrics Research, involved polymerase chain reaction (PCR) testing of 285 samples and viral culture of 160 samples of breast milk from 110 women with confirmed or suspected COVID-19.

The women had donated to a university breast milk biorepository from March to September 2020. Among them, 65 had confirmed COVID-19, 9 had symptoms but tested negative, and 36 had symptoms but weren't tested.

On PCR testing, SARS-CoV-2 subgenomic RNA (sgRNA) was detected in the milk of 7 (6%) women, including 6 of 65 women (9%) with confirmed COVID-19. sgRNA is not live (infectious) virus but genetic material of unclear significance; some scientists believe it may indicate replicating virus.

Testing a second breast milk sample from the 7 women with confirmed COVID-19 1 to 97 days later detected no SARS-CoV-2 sgRNA. None of the babies had clinical evidence of COVID-19. In lab experiments, the researchers could culture infectious SARS-CoV-2 after adding it to breast milk after repeated freeze–thaw cycles, as may occur in the storage and use of breast milk.

The study authors said that while the study was small and may not have captured all factors that indicate the presence of SARS-CoV-2 in breast milk, it is the largest known such study to date and found no evidence that maternal COVID-19 infection rules out breastfeeding.

In a Springer news release, lead author Paul Krogstad, MD, said that breast milk is an invaluable source of nutrition for infants. "In our study, we found no evidence that breastmilk from mothers infected with COVID-19 contained infectious genetic material, and no clinical evidence was found to suggest the infants got infected, which suggests breastfeeding is not likely to be a hazard," he said.
Jan 19 Pediatr Res study
Jan 18 Springer
news release


Study: Remdesivir reduces mechanical ventilation in COVID-19 patients

A randomized control trial published today in the Canadian Medical Association Journal (CMAJ) shows that the antiviral drug remdesivir reduces the use of mechanical ventilation by almost half for patients hospitalized with COVID-19.

To conduct the study, researchers randomized 1,282 patients seen at 52 Canadian hospitals from Aug 14, 2020, to Apr 1, 2021, to be treated with either remdesivir (634 patients) or standard of care (648). Those treated with remdesivir received 200 milligrams (mg) intravenously [IV] on day 0, followed by 100 mg IV daily for 10 days.

Patients who received remdesivir suffered an in-hospital mortality rate of 18.7%, compared with 22.6% in the standard-of-care group (relative risk [RR], 0.83; 95% confidence interval [CI], 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (RR, 0.88; 95% CI, 0.72 to 1.07), the authors said. Only 8% of patients on remdesivir required mechanical ventilation, compared with 15% in the standard-of-care group.

"The benefit of treatment was most apparent for preventing the need for mechanical ventilation, suggesting probable added value for patients with less severe disease to avoid progression during hospital stay," the authors said. "We found more ventilator- and oxygen-free days among patients receiving remdesivir, as well as improved clinical recovery at day 15."

The authors said their study did not control for which variant of the virus patients were infected with, and different variants may have an effect on the antiviral effectiveness of remdesivir.
Jan 19 CMAJ


USDA reports 2 more H5N1 avian flu detections in wild birds

The US Department of Agriculture (USDA) yesterday reported two more highly pathogenic H5N1 avian flu detections in wild birds, just days after announcing the first detection of the Eurasian strain since 2016.

In a statement from its Animal and Plant Health Inspection Service (APHIS), the USDA said one bird that tested positive was from Colleton County in South Carolina, the same area where the first H5N1 detection was found in a hunter-harvested wild duck. The second was from North Carolina's Hyde County, located about 400 miles northeast. Both counties are located near coastal areas.

A list of highly pathogenic avian flu findings on the APHIS website said the latest Colleton County detection involved a blue-winged teal and the Hyde County detection involved a northern shoveler. The viruses were found during testing as part of active surveillance for the disease.

The US H5N1 identifications come shortly after Eurasian H5N1 was detected in wild birds and poultry in Canada's Newfoundland and Labrador region. Recent H5N1 viruses have caused extensive poultry and wild bird outbreaks in Europe, with events also occurring in other parts of the world.

Scientists are closely watching the virus, because it has been found in a few mammals in Europe and has been linked to very rare human infections in people who had very close contact with poultry.
Jan 18 APHIS statement
APHIS list of avian flu detections
Jan 18 CIDRAP News scan

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