Novel microbiome-directed therapy shows promise against recurrent C difficile

News brief

A team of Canadian and US researchers reported last week in JAMA that a high dose of a novel oral microbiome-directed therapy prevented recurrent Clostridioides difficile infection (CDI) compared with placebo.

C difficile
CDC illustration

In the phase 2 trial, conducted at 27 sites in the United States and Canada, investigators aimed to evaluate the efficacy of VE303 (a defined bacterial consortium consisting of eight non-pathogenic, non-toxic commensal strains of Clostridia) at different doses. They randomly assigned 79 adults who'd had one or more prior CDI episodes in the previous 6 months or had a primary case and were at high risk for recurrence to receive a high dose of VE303, a low dose, or placebo orally for 14 days.

The primary efficacy end point, analyzed in three prespecified analyses using successively broader definitions of CDI recurrence, was the proportion of participants with CDI recurrence at 8 weeks.

Among the 74 participants who completed follow-up, the median age was 65.3 years, 70.5% were female, and 96.2% were White. Baseline and clinical characteristics were comparable across all three treatment groups.

Lower recurrence rates

In efficacy analysis 3, which defined CDI recurrence as diarrhea consistent with CDI plus laboratory confirmation or treatment with a CDI-targeted antibiotic, CDI recurrence occurred in 4 of 29 (13.8%) high-dose VE303 patients, compared with 10 of 27 (37.3%) for low-dose VE303, and 10 of 22 (45.5%) for those who received placebo. The odds ratio of CDI recurrence for the high-dose VE303 group versus placebo was 0.19 (90% confidence interval [CI], 0.05 to 0.71).

In follow-up through week 24, only one additional CDI recurrence occurred in the high-dose VE303 group. Most trial participants (76 of 79) experienced one or more treatment-emergent adverse events, which were generally mild or moderate intensity and were gastrointestinal.

The investigators say a larger, phase 3 trial is needed to confirm the findings.

Symptom-based diagnosis captures more long-COVID cases than ICD-10 definition

News brief

long COVID phone searchAn observational study of more than 2 million Medicare beneficiaries aged 65 and older finds that symptom-based testing identified long COVID in 30% of hospitalized patients and 17% of outpatients. Established diagnostic codes captured only 2.6% and 0.49% of those cases, respectively.

The study was published yesterday in PLOS Medicine.

Researchers with the National Institutes of Health used International Classification of Diseases, 10th revision (ICD-10), diagnostic codes to identify cases of COVID-19 and influenza. They used the designated long-COVID code or any of the 11 symptoms included in the World Health Organization (WHO) definition to identify long-COVID cases 1 to 3 months after infection.

Identification of persistent flu symptoms (long flu) for the 2018 and 2019 flu seasons using the same symptom-based definition for long COVID.

Long COVID tied to more severe outcomes

Of 2,071,532 patients who tested positive for COVID-19 from April 2020 to June 2021, the symptom-based definition identified long COVID in 16.6% of hospitalized patients and 29.2% of nonhospitalized patients. The ICD code, however, identified only 2.6% and 0.49%, respectively, of those cases. Of 933,877 flu patients, 24.6% of hospitalized patients and 17.0% of outpatients conformed to the long-flu definition.

Relative to long-flu patients, those with long COVID had higher rates of shortness of breath, fatigue, heart palpitations, loss of smell or taste, and neurocognitive symptoms. Nonhospitalized long-COVID patients had higher odds of any-cause hospitalization (31.9% vs 26.8%; odds ratio [OR], 1.06) and more outpatient visits than long-flu outpatients (average, 2.9 vs 2.5; incidence rate ratio, 1.09).

Relying on specific long COVID diagnostic codes results in significant underreporting.

Long-COVID patients visited an emergency department (ED) less often than long-flu patients, likely because ED usage in general was lower than normal during the study period.

"Relying on specific long COVID diagnostic codes results in significant underreporting," the study authors wrote. "The impact of long COVID on healthcare utilization is higher than long Flu."

Quick takes: CDC details H5N1 virus in Chile's case, more avian flu in US mammals and condors

News brief
  • In an addendum to a H5N1 avian flu technical report, the US Centers for Disease Control and Prevention (CDC) yesterday posted details about Chile's recent human case and findings from a genomic analysis of a sample from the patient. The man, who got sick on March 13, is still isolated in the hospital and is on a ventilator for pneumonia. The virus is nearly identical to H5N1 in wild birds in Chile and is of the same clade affecting birds and poultry elsewhere. The hemagglutinin gene shows no changes that would make it more recognizable to mammalian receptors, and the specimen is closely related to an existing prepandemic candidate vaccine virus.
  • Eight more H5N1 detections in US mammals have been reported, raising the total to 162, according to the latest updates from the US Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS). States include Colorado, New York, Pennsylvania, and Wyoming. The affected animals include six red foxes, a skunk, and a mountain lion.
  • The National Park Service has reported more deaths in endangered condors in the Arizona-Utah flock, raising the total to 20. So far, H5N1 has been confirmed in 10 of the birds. Eight sick birds were collected for supportive care, and 4 of them died shortly after.

Clinicians describe challenge of treating multidrug-resistant war wounds from Ukraine

News brief

In a slide presentation at this week's European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Copenhagen, Denmark, a team of surgeons and infectious disease clinicians highlighted the complexity and multidrug-resistant, polymicrobial nature of some of the war wounds they are seeing in Ukraine.

The presentation focused on 14 patients with highly complex musculoskeletal infections from gunshot and bomb wounds who were treated at the Center for Musculoskeletal Surgery at the Charite-University Hospital in Berlin from March to December 2022. Of the 14, 13 were colonized with multidrug-resistant gram-negative organisms, including Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli, as well coagulase-negative staphylococci, enterococci, and fungal organisms.

Of 25 gram-negative isolates analyzed, 72% were resistant to carbapenems and newer cephalosporins (ceftazidime-avibactam and ceftozolane-tazobactam), 39% were resistant to cefiderocol, 20% to colistin, and 96% to ciprofloxacin.

"We are dealing with a completely new pathogen spectrum than what we would expect to see in Germany," lead author Maria Virginia Dos Santos, MBBS, said in an ECCMID press release. "In these horrific war injuries, we are seeing high incidence of multi-resistant gram-negative pathogens, and all our cases have been polymicrobial infections."

We are dealing with a completely new pathogen spectrum.

Dos Santos said suboptimal surgical and antibiotic treatment in the often unsterile and low-resource conditions of a war zone likely contributed to the complexity of the wounds.

All of the patients required empiric treatment with a combination of antibiotics, along with removal of dead bone and soft tissue, soft-tissue reconstruction, and reconstructive surgery. Two of the patients have been discharged and returned to Ukraine, eight have no signs of infection and are undergoing rehabilitation, two are still undergoing treatment, and two have developed new acute infections.

In two reports published in Eurosurveillance in December 2022, researchers at hospitals in Germany and the Netherlands reported an uptick in multidrug-resistant organisms linked to patients who had fled or were evacuated from hospitals in Ukraine.

Report: Medical oxygen suppliers should do more to address shortages in poor countries

News brief

The world's largest gas producers should seize the opportunity to reduce long-term inequities in access to medical liquid oxygen in low- and middle-income countries (LMICs), according to a report today from the Access to Medicine Foundation.

The Netherlands-based foundation said that, amid the COVID-19 pandemic, Air Liquide, Air Products, Linde, Messer, Nippon Sanso Holdings Corp., and SOL Group showed they can mitigate shortages through efforts such as shifting more production capacity from industrial to medical oxygen and transporting oxygen tankers and trailers on chartered aircraft.

But about half of healthcare facilities in poor countries still don't have reliable access to oxygen, leading to preventable deaths. "This is despite the fact that medical oxygen is included in the World Health Organization's Model List of Essential Medicines, meaning it is a product that should be available in every country’s health system," the report said.

"Medical gases are a small part of these companies' business, yet society needs them to ensure this vital lifeline is available both during emergencies and to meet the daily medical oxygen needs of all health systems," Access to Medicine Chief Executive Officer Jayasree Iyer, MD, PhD, said in the report.

Six priority actions

Air Liquide is the only firm with a clear strategy for ensuring access to oxygen in LMICs, the report said. The others haven't identified specific targets but have reported expanding oxygen to more regions and buying equipment to boost oxygen production.

The report identifies six priority actions:

  • Prioritize, measure, and report progress on medical liquid oxygen
  • Improve affordability for populations and health systems
  • Provide a sustainable supply of oxygen
  • Foster long-term partnerships to close access gaps
  • Support health systems and staff to operate, maintain, and administer medical oxygen systems
  • Plan for emergencies

LMIC healthcare facility infrastructures and fragmented supply chains complicate achieving these goals. "However, the gas companies in [the] scope of this report can play a critical role in helping to overcome some of these challenges, in particular by pursuing and formalising long-term partnerships with governments and global health stakeholders," the authors wrote.

Marburg virus confirmed in another Equatorial Guinea health worker

News brief

One more Marburg virus case has been confirmed in Equatorial Guinea's outbreak, involving a healthcare worker from Bata who was under monitoring after exposure to a previous patient, the head of the World Health Organization (WHO) said today.

At a media briefing, Tedros Adhanom Ghebreyesus, PhD, the WHO's director-general, said the new case was detected on the day of illness onset and that the patient was given antiviral treatment according to government protocols, with support from the WHO.

The new case raises the outbreak total to 16 confirmed cases, of which 11 were fatal. Also, 23 probable cases have been reported, all fatal. Also, the new case puts the number of infections in healthcare workers at five.

Equatorial Guinea is battling its first Marburg virus outbreak, with cases reported across four provinces, with multiple cases reported from Bata, the country's largest city and home to a port and an international airport. A close cousin of Ebola, Marburg virus spreads among people through the body fluids of infected patients.

Wisconsin confirms first CWD detection in Winnebago County

News brief
White-tailed doe
DOE-Oakridge / Flickr

The Wisconsin Department of Natural Resources (DNR) has confirmed chronic wasting disease (CWD) in a deer in Winnebago County, the first time the fatal prion disease has been detected in that county.

The wild deer—a 3-year-old doe —tested positive in the town of Nepeuskun, which is within 10 miles of the Waushara County, Green Lake County, and Fond du Lac County borders. This detection renews a 3-year baiting and feeding ban in the county, as well as renews a 2-year baiting and feeding ban in Waushara County, Green Lake County, and Fond du Lac County.

"Baiting or feeding deer encourages them to congregate unnaturally around a shared food source where infected deer can spread CWD through direct contact with healthy deer or by leaving behind infectious prions in their saliva, blood, feces and urine," the DNR said in a statement on the detection.

CWD has been detected in cervids in North America, Canada, South Korea, and Scandinavia. The Wisconsin DNR first began testing animals in 1999, with the first positive detected in 2002.

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