Narrow-spectrum C difficile antibiotic shows promise in phase 2 study

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C difficile bacteria under microscope — Dr_Microbe / iStock

A narrow-spectrum antibiotic candidate for Clostridioides difficile infection (CDI) was highly effective and well-tolerated in a small phase 2 trial, researchers reported yesterday in The Lancet Infectious Diseases.

In the multicenter, randomized controlled trial, a team led by researchers with Colorado-based biopharmaceutical company Crestone evaluated the safety and efficacy of the company’s CRS3123, a small-molecule protein synthesis inhibitor that targets an enzyme found in C difficile and a few species of gut bacteria. Fifty-eight patients with a primary episode or first recurrence of CDI were randomly assigned to receive one of two dose-levels of CRS3123 or vancomycin, a widely used therapy for CDI.

The primary end point was clinical cure at the test-of-cure (TOC) visit. Rate of CDI recurrence was the secondary end point.

The hope with CRS3123 is that it will be effective against CDI—an infection that causes more than 500,000 hospitalizations and 35,000 deaths a year in the United States—without disrupting many of the beneficial bacteria that live in the gut. Disruption of the gut microbiome by broad-spectrum antibiotics like vancomycin enables C difficile to re-colonize the gut and cause recurrent CDI.

“Alternative treatments that can be effective in the acute infection stage and preserve the normal gut microbiota to reduce the risk of recurrence are needed,” the study authors wrote.

Lower recurrence rates than with vancomycin

Among the 29 patients who received either 200 milligrams (mg) or 400 mg of CRS3123, 28 (96%) experienced clinical cure at the TOC visit, compared with 13 of 14 patients (93%) in the vancomycin group. Recurrence through day 40 occurred in one (7%) of 14 patients in the CRS3123 400-mg group, none of the 13 patients in the 200-mg group, and three (23%) of 13 patients in the vancomycin group.

Treatment-emergent adverse events were primarily gastrointestinal and were mild to moderate in severity across all three treatment groups.

“The safety and efficacy results are promising for this novel, narrow-spectrum agent, and warrant further testing of the drug in phase 3 clinical trials,” the authors concluded.

Antiviral use in kids with flu dropped during pandemic

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Liz Szabo, MA

The use of antiviral treatments in children hospitalized for influenza fell sharply during the COVID-19 pandemic, according to a study published last week in Pediatrics.

While 48% to 57% of hospitalized children received antivirals for flu before the pandemic (December 2016 to March 2020), a team led by researchers from the University of Vanderbilt Medical Center found that 38% of these kids received the medications in 2021 to 2022, along with 46% in 2022 to 2023.

Before the pandemic, use of antivirals had grown steadily for several years. Research shows that antivirals can reduce the number of days children experience flu symptoms and potentially reduce the risk of complications.

The American Academy of Pediatrics and other expert groups recommend prompt antiviral treatment in children with suspected or confirmed influenza who are hospitalized; have severe illness; or are at higher risk of influenza complications, even without a confirmed lab test.

In the study, which included 1,560 children hospitalized with influenza, kids were more likely to received antivirals if they had an underlying medical condition, were vaccinated against flu, had clinical influenza testing, were admitted directly to the intensive care unit, and if they had symptoms for two or more days before seeking care.

Antiviral medications included in the study, which was funded by the Centers for Disease Control and Prevention (CDC), were oseltamivir, peramivir, baloxavir, and zanamivir.

Flu vaccinations also dropped during the pandemic

The percentage of hospitalized children vaccinated against seasonal flu fell from 47% before the pandemic to 33% in the late pandemic period of July 1, 2021 to June 30, 2023.

Although the study didn’t explore reasons for the “concerning decline” in antivirals, researchers noted that misinformation and mistrust of the medical system increased during the pandemic. They also suggested that parents and health care providers “may underestimate the severity of influenza in children, perceiving it as a self-limiting illness despite evidence of severe complications, including hospitalizations and deaths, even in otherwise healthy children."

Philanthropic groups announce $60 million in grants for antibiotic discovery

News brief

Chris Dall, MA

Scientists working in laboratory — SeventyFour / iStock

A coalition of philanthropic groups yesterday announced $60 million in grants to researchers working on new antibiotics for some of the most challenging bacterial pathogens.

The Gates Foundation, Novo Nordisk Foundation, and Wellcome said the money, awarded through the Gram-Negative Antibiotic Discovery Innovator (Gr-ADI), will go to research teams in 17 countries, including Ghana, South Africa, and Brazil. The groups launched Gr-ADI in January 2025 to address the lack of novel antibiotics for gram-negative bacteria, which pose a challenge for antibiotic developers because of their tough outer membrane.

More than 500 proposals submitted

Drug-resistant gram-negative bacteria are a leading cause of deaths from antimicrobial resistance (AMR). When Gr-ADI launched, officials with the project said the first round of grants would focus on the discovery of antibiotics with broad-spectrum activity against Enterobacteriales, particularly Klebsiella, which is on the World Health Organization’s list of priority pathogens.

More than 500 proposals were submitted to Gr-ADI, which officials say is a first-of-its-kind consortium where research teams and funders “openly share data and learnings and work collectively to accelerate the discovery of urgently needed antibiotics.”

"AMR is undermining our ability to treat even routine infections, putting millions of lives at risk, especially in lower- and middle-income countries," Trevor Mundel, MBBCh, PhD, president of global health at the Gates Foundation said in a press release. "Gr-ADI is about accelerating discoveries that can translate into new antibiotics faster, so countries have the tools they need to protect their populations now and in the future."