News Scan for Jan 21, 2022

News brief

No reduced fertility with COVID vaccines, but infection ups risk in men

A cohort study of more than 2,000 US and Canadian women indicates that COVID-19 vaccination does not impair fertility—but men who become infected with SARS-CoV-2 may experience short-term reduced fertility, according to surveys of the women's partners.

In the study, published yesterday in the American Journal of Epidemiology, Boston University (BU) researchers analyzed survey data on COVID-19 vaccination and infection, and fertility, among female and male participants in the Pregnancy Study Online (PRESTO), an ongoing study funded by the National Institutes of Health that enrolls women trying to conceive and follows them from before conception through 6 months after delivery. Participants included 2,126 women in the United States and Canada who provided information on themselves and their male partners from December 2020 to September 2021.

The investigators conducted follow-up through November 2021.

The researchers calculated the per–menstrual cycle probability of conception using self-reported dates of participants' last period, typical menstrual cycle length, and pregnancy status. They found that the fertility rates among female participants who received at least one dose of a COVID vaccine were nearly identical to unvaccinated female participants. Fertility was likewise similar for male partners who had received at least one dose of a COVID vaccine compared with unvaccinated peers.

In contrast, men who tested positive for COVID-19 within 60 days of a given cycle had reduced fertility compared with men who never tested positive or with men who tested positive at least 60 days prior. This finding did not hold true for the women and supports previous research that has linked COVID-19 infection in men with poor sperm quality and other reproductive dysfunction, according to a BU School of Medicine news release.

First author Amelia Wesselink, PhD, MPH, said in the release, "Our study shows for the first time that COVID-19 vaccination in either partner is unrelated to fertility among couples trying to conceive through intercourse. Time-to-pregnancy was very similar regardless of vaccination status."

Senior author Lauren Wise, ScD, said, "The prospective study design, large sample size, and geographically heterogeneous study population are study strengths, as was our control for many variables such as age, socioeconomic status, preexisting health conditions, occupation, and stress levels."
Jan 20 Am J Epidemiol study
Jan 20 BU School of Medicine news release

Moderna vaccine outperforms Pfizer against Delta breakthrough cases

A study yesterday in JAMA shows the Moderna mRNA vaccine was more protective than the Pfizer-BioNTech mRNA vaccine at preventing breakthrough COVID-19 cases during the US Delta surge.

The study was based on electronic health records from 637,000 fully vaccinated patients from 63 healthcare organizations across the United States, dated from July to November 2021. Full vaccination was considered to be 2 or more weeks since a second dose of mRNA vaccine. Patients who were boosted (given a third dose) or who had prior COVID-19 infections were excluded from the study.

Moderna recipients were less likely to be infected with breakthrough cases and less likely to be hospitalized. There were 2.8 breakthrough cases per 1,000 people in those vaccinated with Pfizer and 1.6 cases per 1,000 with Moderna in November 2021, and the 60-day hospitalization rate was 13.3% for Pfizer recipients and 12.7% for Moderna.

Neither group had high mortality rates: The 60-day mortality was 1.14% (35/3,078) and 1.10% (207/18,737) for Moderna and Pfizer recipients, respectively.

"Although there is a difference in breakthrough infections, both vaccines are highly protective against SARS-COV2 infection and especially against the most severe consequences of infection," said study coauthor Pamela B. Davis MD, PhD, in a Case Western University press release.
Jan 20 JAMA study
Jan 20 Case Western University press release

US flu levels drop slightly for second consecutive week

For the second week in a row, US flu markers showed a slight decline, though activity is still elevated and will likely continue for several more weeks, the US Centers for Disease Prevention and Control (CDC) said today in its weekly update.

The percentage of outpatient visits for flulike illness is still above the national baseline, but it dropped from 4.3% to 3.5% last week. The CDC has said that flu is just one of multiple respiratory viruses contributing to flulike illness levels and that flu levels vary in different parts of the country.

The number of states reporting high or very high flu activity, another indicator of clinic visits for flu, dropped from 21 to 14 last week. Hospitalizations declined, and the percentage of respiratory specimens that tested positive for flu at clinical labs dropped from 2.2% to 1.8%.

Two more pediatric flu deaths were reported, bringing the season's total to five. Both occurred during the week ending Jan 15. One involved the H3N2 strain, and the other was from an unsubtyped influenza A strain.

Very little influenza B was detected, and, of influenza A strains, H3N2 is still overwhelmingly dominant, making up 100% of subtyped samples at public health labs. Most H3N2 viruses are genetically related to the vaccine virus; however, the CDC said it is seeing some antigenic differences as the virus continues to evolve.
Jan 21 CDC FluView report

Nigeria reports more vaccine-derived polio cases

Nigeria is the only country that reported new polio cases this week, part of ongoing circulating vaccine-derived poliovirus type 2 (cVDPV2) activity in a number of African countries, the Global Polio Eradication Initiative (GPEI) said in its latest weekly update.

All 3 cases are included in the country's total for 2021, which now stands at 388. The new cases are in Kano, Katsina, and Borno states.

The WHO declared polio a public health emergency of international concern in May of 2014. Since then, wild poliovirus cases have dropped sharply, but a number of countries are still reporting vaccine-derived polio cases.

At the WHO's last polio emergency committee meeting, the group said some of its top concerns are cross-border spread of vaccine-derived polio and the unpredictable wild poliovirus type 1 situation in Afghanistan.
Jan 20 GPEI update
Nov 24, 2021, CIDRAP News scan

Stewardship / Resistance Scan for Jan 21, 2022

News brief

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

ASP Scan (Weekly) for Jan 21, 2022

News brief

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Phase 3 trial finds oral microbiome therapy cuts risk of recurrent C diff

TB Alliance receives $30 million from USAID for new TB treatments

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.

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