Study reveals how microbiota-based treatment may help prevent recurrent C diff

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C difficile bacteria
Artur Plawgo / iStock

Analysis of data from a phase 3 clinical trial provides some clues as to how a microbiota-based treatment helps prevent recurrent Clostridioides difficile (rCDI) infection, researchers reported yesterday in the Journal of Infectious Diseases.

For the study, researchers analyzed stool samples from participants in PUNCH CD3, a randomized clinical trial that found the fecal microbiota-based live biotherapeutic Rebyota (RBL) was clinically superior to placebo in preventing rCDI. The researchers wanted to investigate the extent to which RBL restores the balance of bacteria and bile acid (BA) in the gut microbiome following antibiotic therapy, which is typically the first line of treatment for rCDI patients but often causes further gut microbiome disruption and increases the risk of future recurrence.

RBL linked to microbiota, BA changes    

Stool samples were collected from participants who received a dose of RBL or placebo at baseline and 1, 4, and 8 weeks after treatment. Sequencing of those samples revealed that, before administration, Gammaproteobacteria and Bacilli dominated the microbiota community, and primary BAs were more prevalent than secondary BAs in trial participants. These characteristics are associated with reduced resistance to C difficile colonization, the study authors note. 

"Thus, trial participants were dysbiotic before study treatment in ways that could enable CDI recurrence," they wrote.

In participants who responded to treatment with RBL or placebo, clinical success after administration correlated with shifts to predominantly Bacteroidia and Clostridia, a significant increase in the Microbiome Health Index, and a shift from primary to secondary BAs. But several microbiota and BA changes were more extensive in RBL-treated responders than in placebo-treated responders, and microbiota changes correlated with BA changes.

"Overall, the microbiome and BA analyses herein support a model in which Bacteroidia restoration, decreased Gammaproteobacteria levels, and the increased metabolism of primary to secondary BAs were potential drivers of RBL clinical efficacy," the authors concluded.

RBL was approved by the US Food and Drug Administration for the prevention of rCDI in 2022 based on data from PUNCH CD3 and other clinical trials.

CDC reports 2 more variant flu cases, both with swine exposure

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Pig race at fair
Brent Moore / Flickr cc

The Centers for Disease Control and Prevention (CDC) today reported two more variant influenza cases, one in Ohio and the other in Pennsylvania, in people who had contact with pigs.

Both patients are adults, recovered after hospitalization, and had underlying health conditions, the CDC said in its weekly influenza report.

Cases involve 2 different strains

The patient from Ohio had a variant H1N1 (H1N1v) infection and got sick after exposure to pigs at an agricultural event. Meanwhile, Pennsylvania's patient had a variant H1N2 (H1N2v) infection and had occupational exposure to swine.

So far 7 variant flu cases have been reported during the 2024-25 flu season in the United States, 4 from H1N2v, 2 from H3N2v, and 1 from H1N1v.

No symptoms were reported in the patients' contacts, and no related human-to-human cases have been identified.

Sporadic human infections with swine flu occur in the United States and other countries, most often in people who have contact with pigs or their environments. Many of the cases in the United States occur during the summer months, when agricultural fairs take place.

CDC ends its probe of cucumber Salmonella outbreak after 551 cases

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Pile of cucumbers
Bill Couch / Flickr cc

The US Centers for Disease Control and Prevention (CDC) yesterday declared its investigation into a multistate Salmonella outbreak tied to cucumbers over after 551 cases and 155 hospitalizations, an increase of 102 cases and 30 hospitalizations since its last update on July 2.

"Epidemiologic, traceback, and laboratory data showed that cucumbers were contaminated with Salmonella and made people sick," the CDC said. "Testing identified the Salmonella Braenderup outbreak strain in untreated canal water used by a grower in Florida. 

"An additional grower was identified as a likely source of illnesses in this outbreak. Cucumbers from both of these growers are no longer in season and products are no longer on shelves."

On May 31, Fresh Start Produce Sales Inc. issued a cucumber recall because of the outbreak. But the CDC said, "Recalled cucumbers did not account for all the illnesses in this outbreak."

Two outbreak strains

Of the 551 illnesses, 269 people were infected with the Salmonella Braenderup strain and 282 people with Salmonella Africana. Illness-onset dates range from March 11 to July 26, with patient ages ranging from less than 1 year to 94, with a median age of 48. Sixty-eight percent of patients are female, and 84% are White.

Recalled cucumbers did not account for all the illnesses in this outbreak.

New York state reported the most cases, 69, followed by Pennsylvania (68), Florida (60), Georgia (48), and Virginia (48). Thirty-four states and the District of Columbia confirmed cases.

"The true number of sick people in this outbreak is likely much higher than the number reported, and the outbreak may not be limited to the states with known illnesses," the CDC said.

High-dose, adjuvanted flu vaccines better protect seniors from symptoms, hospital stays, study finds

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Older woman getting vaccinated
James Gathany / CDC

High-dose (HD) and adjuvanted influenza vaccines offered the best protection for people aged 65 years and older against symptoms and hospitalization during the 2022-23 flu season, concludes a real-world study published this week in Clinical Infectious Diseases.

High-dose flu vaccines contain four times the standard dose (SD), while adjuvanted vaccines contain an extra immune-boosting ingredient. In 2022, the US Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommended high-dose, adjuvanted, or recombinant (cell-based) vaccines over SD vaccines for older adults, who are at elevated risk for severe disease and flu-related hospitalization and death.

Kaiser Permanente Southern California researchers retrospectively assessed the comparative vaccine effectiveness (cVE) of HD, adjuvanted, and SD cell-based flu vaccines versus SD egg-based vaccines. 

Participants were 495,119 adults with a median age of 73 years who received a flu vaccine dose from August through December 2022 and were followed up to May 2023. Of all participants, 54.9% were women and 46.3% were White.

"Overall, influenza vaccine effectiveness (VE) has remained low (<50% between 2014 and 2022), particularly in seasons of mismatch between the vaccine and circulating strains," the study authors wrote. "To improve vaccine platforms and production, high-dose (HD), adjuvanted, recombinant, and standard-dose (SD) cell-based vaccines became available in addition to egg-based SD vaccines."

Adjuvanted vaccines most effective

In total, 74.8% of participants received high-dose flu vaccines, and the remainder received SD egg-based (13.9%), SD cell-based (6.5%), or adjuvanted (4.7%) vaccines.

Our research showed that there were advantages for older people to receive high-dose or adjuvanted flu vaccines over the standard vaccine.

Jennifer Ku, PhD, MPH

Adjusted cVEs against flu-related medical visits in the HD, adjuvanted, and SD cell-based vaccine groups were 9.1%, 16.9%, and −6.3%, respectively. Adjusted cVEs against hospitalization in the three groups were 25.1%, 61.6%, and 26.4%, respectively.

"Our research showed that there were advantages for older people to receive high-dose or adjuvanted flu vaccines over the standard vaccine," lead author Jennifer Ku, PhD, MPH, an infectious disease epidemiologist, said in a Kaiser Permanente news release. "While seasonal variation exists, it is expected that seniors will continue to benefit from flu vaccines that are stronger than the traditional standard-dose vaccines."

DoD-funded study to collect data on antibiotic-resistant war wounds in Ukraine

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Wounded soldiers in Ukraine
President of Ukraine / Flickr cc

The University of Colorado (UC) School of Medicine announced yesterday that it's been awarded $5 million from the US Department of Defense (DoD) to collect and study data on antibiotic-resistant wounds linked to the war in Ukraine.

Wound infections caused by multidrug-resistant organisms have substantially increased in Ukraine since Russian forces invaded the country in 2022, complicating treatment for frontline providers. Yet no systematic data for wound infections exist in Ukraine. Through the project, called the Antimicrobial Resistance Research to Improve Outcomes of Traumatic Wounds study (ARROW) study, UC researchers will work with researchers in Ukraine to create infrastructure for collecting such data.

Wound infection a 'top concern' for US military

The project aims to enroll up to 1,000 patients and collect data on injury and wound characteristics, molecular testing, and clinical outcomes, with researchers in Ukraine collecting specimens at three frontline hospitals and two referral centers over the next 2 years. UC researchers say these data will help providers in Ukraine during the current conflict and enable clinical trials to test solutions that help prevent and treat wound infections in future conflicts.

"Wound infection is consistently identified as a top concern in Ukraine and the U.S. military, which is why we are moving forward on this project first," Adit Ginde, MD, MPH, a professor of emergency medicine at UC and principal investigator on the project, said in a UC press release. "The first step is actually describing the problem in a more systematic way and then quickly pivot[ing] to clinical trials."

Roman Fishchuk, MD, a researcher at Central City Clinical Hospital of Ivano-Frankivsk in western Ukraine, will lead the in-country data collection effort.

“I'm grateful to our colleagues at the University of Colorado for being brave, working with us, and being so proactive," Fishchuk said. "This partnership is inspiring and helps us do our job and think about research in new ways."

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