FDA clears investigational new drug application for bacteriophage therapy

Biotechnology company Adaptive Phage Therapeutics (APT) announced last week that the Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for bacteriophage therapy for the treatment of prosthetic joint infections (PJIs).

Bacteriophages, or phages, are viruses that infect bacteria and can be used to fight bacterial infections.

APT officials say the IND clearance will enable them to initiate a phase 1/2 trial to evaluate the safety and surgery-sparing effect of phages in patients with PJIs who are also being treated with antibiotics. The phages are selected from PhageBank, the company’s library of purified phages covering a wide spectrum of specific bacterial diseases, and precisely matched to the bacteria causing the infection using a phage susceptibility test that APT has developed with the Mayo Clinic.

APT will conduct the randomized, controlled trial in collaboration with the Mayo Clinic starting in the second quarter of 2021.

“Phage therapy represents a potentially game-changing new treatment option for PJI and other multi-drug resistant or biofilm-mediated bacterial infections, where current patient outcomes can include loss of limb or even life,” Gina Suh, MD, an infectious disease specialist at Mayo Clinic who is leading the collaboration with ATP, said in a company press release.

APT says the first interim data analysis from the trial is expected in the first quarter of 2022.
Feb 10 APT press release

Increased resistance, gene exchange found in Campylobacter from meat

In a study last week in PLOS One, researchers at North Carolina State University (NC State) identified an increase in antimicrobial resistance (AMR) genes and virulence factor distribution in Campylobacter samples isolated from animals and food.

In the study, researchers from NC State’s College of Veterinary Medicine evaluated 541 Campylobacter isolates collected from live chickens, turkeys, swine, and cattle, as well as poultry carcasses and retail meat, in North Carolina from January 2018 through December 2019. Campylobacter coli was most prevalent on farms and at production facilities, comprising most isolates from live turkeys (100%), swine (94%), chicken (54%), and chicken carcasses (60%), while Campylobacter jejuni was the prominent species in retail chicken meat (69%).

Whole-genome sequencing of the isolates revealed that 90.4% of C coli and C jejuni isolates (489/541) contained at least one AMR gene and 43.1% (233/541) contained resistance genes to three or more antibiotic classes—a proportion higher than was found in 2017 National Antimicrobial Resistance Monitoring System surveillance. C coli isolates were twice as likely as C jejuni isolates to carry three or more resistance genes (odds ratio, 1.9; 95% confidence interval, 1.3 to 2.7).

AMR gene frequencies were highest against tetracyclines (64.3%), beta-lactams (63.6%), aminoglycosides (38.6%), macrolides (34.8%), quinolones (24.4%), lincosamides (13.5%), and streptothricins (5%).

The analysis also found that 57.6% of C jejuni (114/198) carried virulence factors for Guillain-Barré Syndrome, which can be triggered by Campylobacter infection, and revealed further evidence of C coli and C jejuni interspecies genomic exchange. The authors say that high levels of interspecies genomic exchange between the two species may alter pathogen survivability and resistance trends, and could pose a greater threat to public health.

In 2019, Campylobacter was the leading US cause of foodborne illness.

“This study shows that genomic exchange is happening between C. coli and C. jejuni, and that there is increasing antimicrobial resistance in Campylobacter found in N.C. poultry production,” lead author Dawn Hull, a PhD student at NC State, said in a university press release. “Campylobacter is the worldwide leading cause for foodborne illness, so tracking this exchange is crucial to preventing transmission and providing future treatments.”
Feb 11 PLOS One study
Feb 15 NC State press release