Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
Phase 3 trial finds oral microbiome therapy cuts risk of recurrent C diff
In a phase 3 trial, an investigational oral microbiome therapy was superior to placebo in reducing the risk of recurrent Clostridioides difficile infection, researchers reported yesterday in the New England Journal of Medicine.
The double-blind, randomized trial involved patients who had had three or more episodes of C difficile infection within 12 months and had resolution of symptoms following standard-of-care antibiotic therapy. From July 2017 through September 2020, the patients were enrolled and randomly assigned 1:1 to receive SER-109, a therapeutic composed of live purified Firmicutes bacterial spores developed by Seres Therapeutics (which funded the study), or placebo once daily for 3 days. The primary efficacy objective was to show the superiority of SER-109 over placebo in reducing the risk of C difficile recurrence over 8 weeks.
Of the 281 patients screened for the trial, 182 were enrolled, and 149 completed 8 weeks of follow-up. The percentage of patients with recurrence was significantly lower in in the SER-109 group than in the placebo group (12% and 40%, respectively; relative risk, 0.32; 95% confidence interval [CI], 0.18 to 0.58; P < 0.001).
SER-109 also led to less frequent recurrence than placebo in analyses stratified according to age (relative risk, 0.24 [95% CI, 0.07 to 0.78] for patients younger than 65 years of age and 0.36 [95% CI, 0.18 to 0.72] for those 65 years and older) and antibiotic received (relative risk, 0.41 [95% CI, 0.22 to 0.79] with vancomycin and 0.09 [95% CI, 0.01 to 0.63] with fidaxomicin).
Most adverse events were mild to moderate and were gastrointestinal in nature, with similar numbers in the two groups. SER-109 dose species were detected as early as week 1 and were associated with bile-acid profiles that are known to inhibit C difficile spore germination.
"In patients with recurrent C. difficile infection, achievement of a sustained clinical response can be made more likely with a two-pronged treatment paradigm of antibiotics followed by a microbiome therapeutic," the study authors wrote. "Insights into the pharmacologic properties of this oral microbiome therapeutic have implications not only for treatment of recurrent C. difficile infection but also for other diseases with pathogenesis that may be rooted in microbiome disruption."
Jan 20 N Engl J Med abstract
TB Alliance receives $30 million from USAID for new TB treatments
The nonprofit TB Alliance announced yesterday that it has received $30 million in funding from the US Agency for International Development (USAID) to develop new treatments for tuberculosis (TB) and optimize current treatments so that they can be used in children.
TB Alliance will also use the funding, which will be administered over 5 years, to strengthen health systems in high-TB-burden countries so that all TB patients can get proper treatment.
A recent report from the World Health Organization found that the COVID-19 pandemic has reversed years of progress against TB, and that 1.5 million people died from TB in 2020—up from 1.4 million in 2019. It was the first global increase in TB deaths in more than a decade.
"While the world was focused on the COVID-19 pandemic, the TB pandemic tightened its grip on the most impoverished parts of the world," TB Alliance CEO and President Mel Spigelman, MD, said in a press release. "This is the danger we face in letting older diseases linger instead of eradicating them. We are grateful for the support and collaboration of partners like USAID; only by working together can we make up the ground that has been lost in the past two years."
TB Alliance has played a critical role in advocating for and developing new TB treatments, including pretomanid, a key new element of the shorter treatment regimen for multidrug-resistant TB. The group says its drug development work will continue to focus on finding new drug candidates and developing child-friendly formulations of current drugs.
Jan 20 TB Alliance press release
Paper highlights use of pre-adapted phage against a pan-resistant infection
Originally published by CIDRAP News Jan 19
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
Originally published by CIDRAP News Jan 19
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
