Investigational C diff antibiotic significantly reduces recurrence in phase 3 trial

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An investigational antibiotic developed for treating Clostridioides difficile infection (CDI) did not meet superiority for sustained clinical response (SCR) in a randomized clinical trial but significantly reduced CDI recurrence and preserved microbiome diversity compared with vancomycin, researchers reported today in Clinical Infectious Diseases.

C diff bacteria
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For the trial, which was conducted at 157 sites in 26 countries, adults with CDI were randomized 1:1 to receive 10 days of ridinilazole—a narrow-spectrum antibiotic with targeted activity against C difficile—or 10 days of vancomycin. The primary endpoint was SCR, defined as clinical response and no recurrent CDI (rCDI) through 30 days after end of treatment, in the modified intention-to-treat (mITT) population. Secondary endpoints included rCDI and change in relative abundance of microbiome-derived secondary bile acids (SBAs).

53% reduction in rCDI

Ridinilazole and vancomycin achieved an SCR of 70% and 73%, respectively, for an absolute treatment difference of 2.2% (95% confidence interval [CI], –4.2% to 8.6%), which did not meet the superiority criteria. But ridinilazole resulted in a relative 53% reduction in the rCDI rate compared with vancomycin (8.1% in the ridinilazole group vs 17.3% in the vancomycin group; absolute treatment difference, –9.2%), with subgroup analyses showing a consistent benefit for ridinilazole in high-risk groups.

Ridinilazole also increased microbiome diversity and SBAs and did not increase the resistome, while vancomycin worsened CDI-associated dysbiosis, reduced SBAs, and increased the resistome. Adverse events were similar for both treatment groups (47.1% for ridinilazole vs 47.2% for vancomycin), with the majority considered mild to moderate in severity, and adverse events leading to discontinuation of the study drug were lower in the ridinilazole group (0.8%) than in the vancomycin group (2.9%).

Trial investigators say the reduction in CDI recurrence is likely related to ridinilazole's microbiome-sparing specificity, which has been demonstrated in previous studies.

"The observed reduction in rCDI is supportive of the mechanism of action of this highly selective antibiotic that has a minimal impact on the human microbiome," they wrote.

CDC: Acute flaccid myelitis cases low since 2018, for reasons unknown

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In 2014, 2016, and 2018, the United States saw an uptick in enterovirus-D68 (EV-D68) infections and a subsequent rise in acute flaccid myelitis (AFM) cases, a severe neurologic condition that can result in paralysis.

The pandemic likely disrupted the biannual pattern of infection in 2020, but an uptick in EV-D68 respiratory illnesses in 2022 did not lead to a matching increase in AFM cases, according to findings in Morbidity and Mortality Weekly Report. AFM cases have remained low since 2018, for reasons unknown, the authors said.

The Centers for Disease Control and Prevention (CDC) has monitored AFM cases annually by tracking case reports of acute flaccid limb weakness with any spinal-cord gray-matter lesion on magnetic resonance imaging. During 2018, 2019, 2020, 2021, and 2022, a total of 238, 47, 33, 28, and 47 confirmed AFM cases, respectively, were reported to the CDC.

No EV-D68 found in recent AFM cases

The average age of AFM patients has also increased since 2018, from 5.1 years to 8 years in 2021 and 7.1 years in 2022. AFM cases after 2018 also had less upper-body paralysis and febrile illness. And despite widely circulating EV-D68 causing respiratory illness in 2022, EV-D68 was detected in no patents with AFM in 2020 through 2022.

"Despite apparently increased EV-D68 circulation and EV-D68–associated respiratory disease among children, the reason why an increase in AFM cases did not occur in 2022 is unclear; possibly, EV-D68 viruses circulating in 2022 were less neurotropic or less likely to cause neurologic disease than were viruses circulating during 2014, 2016, and 2018," the authors wrote.

Despite apparently increased EV-D68 circulation and EV-D68–associated respiratory disease among children, the reason why an increase in AFM cases did not occur in 2022 is unclear.

The authors also said co-circulating respiratory viruses in 2022, including respiratory syncytial virus (RSV) and COVID-19, may have affected immune responses to EV-D68 and provided protection against neurologic disease.

British Columbia confirms first cases of CWD

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Mule deer
Mark Moschell / Flickr cc

British Columbia (BC) has reported its first cases of chronic wasting disease (CWD).

The BC Wildlife Federation (BCWF) announced two cases of the fatal neurodegenerative prion disease in a male mule deer and a female white-tailed deer south of Cranbrook in the Kootenay region, in the southeastern part of the province.

Officials said they have been monitoring the high-risk wildlife management areas of southeastern British Columbia that abut areas with outbreaks in Alberta, Montana, and Idaho.  

"We have been watching CWD spread province to province, state to state for at least 20 years, so this is terrible news for British Columbians," Jesse Zeman, BCWF executive director, said in the news release. "CWD is devastating to cervid populations. Continued vigilance and testing are key to organizing preventative measures." 

Call for better policies

Officials will ask for input and support from the CWD Advisory Committee and Regional Working Groups in the coming days, they said.

"We have failed our wildlife populations once again by underfunding the resources needed to manage them for the past 50 years," Steve Hamilton, BCWF advocacy coordinator, said in the release. "Politicians should take this as a reminder that their actions and policies matter and we will be calling for much, much better for our wildlife in the upcoming elections." 

Caused by misfolded proteins called prions, CWD isn't known to infect humans or other non-cervid animals, but experts worry it could jump species. The Centers for Disease Control and Prevention recommends against consuming meat from obviously ill animals or those that test positive for CWD.

Letter highlights limitations of antibiotic trials for pediatric pneumonia

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Doctor with chest x-ray
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A research letter published today in JAMA Network Open suggests that studies supporting the efficacy of lower doses and shorter courses of antibiotics for children with community-acquired pneumonia (CAP) may be limited by a lack of children that truly have bacterial pneumonia.

Using the same criteria as the CAP-IT trial, which found that a lower dose of amoxicillin in children with CAP was non-inferior to a higher dose and a 3-day duration was non-inferior to 7 days, researchers with Boston Children's Hospital and Harvard Medical School enrolled 507 patients aged 3 months to 6 years who presented with clinical signs of CAP. But unlike the CAP-IT trial, which based inclusion on clinical judgment alone, all children in the study underwent chest radiography to confirm the CAP diagnosis.

Of the 507 children (median age, 2.1 years; 54.8% male), 154 (30.3%) had radiographic pneumonia, 49 (9.7) had equivocal radiographs, and 304 (60%) had no radiographic pneumonia. Among the children without radiographic pneumonia, 252 (82.9%) were discharged without antibiotics. Overall, 245 children (48.3%) who satisfied the inclusion criteria recovered without antibiotics.

"We hypothesize that most antibiotic trials in pediatric CAP include many patients without pneumonia and thus may be underpowered to identify true differences in outcomes for children with bacterial pneumonia," the study authors wrote.

While studies that support reducing the intensity of antibiotic use in children with respiratory illness are important, they add, "widespread use of deintensified antibiotic regimens for all children with pneumonia, particularly those with lobar consolidations, may be premature given the paucity of evidence supporting their efficacy for these populations."

We hypothesize that most antibiotic trials in pediatric CAP include many patients without pneumonia and thus may be underpowered to identify true differences in outcomes for children with bacterial pneumonia.

Quick takes: Measles in LA, global polio cases, raw milk Campylobacter outbreak

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  • The Los Angeles County Department of Public Health yesterday announced that a measles infection has been confirmed in a resident who traveled through Los Angeles International Airport while infectious on January 25. The individual arrived on a Turkish Airlines flight at 5 pm that afternoon. Department officials warned that people who were at terminal B may have been exposed and said they and the Centers for Disease Control and Prevention (CDC) are notifying certain passengers on the flight who may have been exposed. The new detection comes just a week after the CDC warned health providers about a rise in measles importations in recent weeks, part of a global increase in measles activity.
  • Six countries—mostly in Africa—reported more polio cases this week, all involving vaccine-derived viruses, the Global Polio Eradication Initiative said in its latest update. All were detected in 2023 and were added to that year's totals. In Africa, Chad reported two more cases involving circulating vaccine-derived poliovirus type 2 (cVDPV2), both from the same province. The Democratic Republic of Congo reported one cVDPV2 case and three linked to circulating vaccine-derived poliovirus type 1 (cVDPV1). Guinea reported eight more cVDPV2 cases from four different provinces, and Niger and Nigeria both added a few more cVDPV2 cases. In the Middle East, Yemen reported one more cVDPV2 case, bringing its 2023 total to four.
  • The Pennsylvania Department of Agriculture this week urged consumers to discard raw milk sold by Conoco View Dairy following reports of 11 Campylobacter infections in December and January in people and tests that confirmed Campylobacter in the dairy's products. The products were sold at the dairy's retail outlet in Perry County and were delivered to retail outlets, people's homes, and drop-off points.

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