Cambodia reports new fatal H5N1 avian flu case

News brief

On the heels of two human H5N1 avian flu cases in Cambodia in January, the country has reported a third 2024 case, which involves a 9-year-old boy who died from his infection, according to a health ministry statement translated and posted by Avian Flu Diary, an infectious disease news blog.

ducks and chickens
marty8801 / iStock

The boy is from Kratie province in the northeastern part of the country. The cases announced last month were in two different provinces, Prey Veng and Siem Reap.

Like the other cases, investigators found that poultry had died at the patient's home. Also, the ministry said the birds that died were eaten.

Recent resurgence

Cambodia has now reported nine H5N1 cases since 2023, part of a resurgence that follows a decade long lapse in cases.

It's not yet known what H5N1 clade sickened the boy, but genetic analysis of samples from the earlier recent cases found that the virus belongs to an older H5N1 clade (2.3.2.1c) that circulates in poultry in some Asian countries, not the newer one (2.3.4.4b) currently circulating in multiple world regions.

Yesterday the World Health Organization (WHO) updated its risk assessment on H5N1 in Cambodia, adding more details about the year's first two cases. It said though the risk to the general population remains low, sporadic human infections will likely continue in rural Cambodia and other areas where the virus still circulates in poultry.

Early estimates of RSV drug show 70% protection against hospital illness

News brief

Real-world efficacy data from Spain indicate that the RSV drug nirsevimab (Beyfortus) is at least 70% effective at preventing RSV hospitalizations in infants under 9 months old, according to new research in Eurosurveillance.

Spain was one of the first countries to introduce nirsevimab as universal RSV prophylaxis (prevention) into its national immunization program for all infants born on April 1, 2023, and after.

In the study, researchers assessed the effectiveness of nirsevimab against hospital admission for RSV for babies across nine hospitals in three Spanish regions. The surveillance period lasted from October 1, 2023, to between December 31, 2023, and January 10, 2024, depending on the hospital.

Easing pressure on healthcare systems

Overall, 166 infant admissions for lower respiratory tract infections included, of which 95 were positive for RSV and 73 were aged 0 to 3 months.

Among all 95 RSV cases, 56 (59%) had been immunized, the authors said.

The immunisation with nirsevimab is expected to alleviate the high pressure on the healthcare systems, especially during winter periods.

Effectiveness against hospitalization was estimated for each region and was as follows: 69.3% (95% confidence interval [CI], 36.4% to 86.2%), 86.9% (95% CI, 77.1% to 92.9%) and 97.0% (95% CI, 87.7% to 99.6%) in Valencia, Murcia and Valladolid, respectively.

"Our estimates indicate that nirsevimab effectiveness was greater than 70% in infants under 9 months of age who were candidates to receive the immunisation. The lack of protection in the RSV-negative hospitalisations supports the estimates," the authors wrote. "In Spain, 3.2 per 100 infants under 6 months of age are hospitalised for an RSV bronchiolitis. The immunisation with nirsevimab is expected to alleviate the high pressure on the healthcare systems, especially during winter periods."

CDC issues new antibiotic prophylaxis guidelines for invasive meningococcal disease contacts

News brief
Neisseria meningitidis
Dan Higgins / CDC

With the number of invasive meningococcal disease cases caused by ciprofloxacin-resistant strains of Neisseria meningitidis rising, the Centers for Disease Control (CDC) yesterday published new guidelines for when other antibiotic prophylaxis (prevention) options should be considered for close contacts of patients.

Published in Morbidity and Mortality Weekly Report, the guidelines note that while antibiotic resistance in N meningitidis has been uncommon in the United States, 29 cases of invasive meningococcal disease caused by ciprofloxacin-resistant strains were reported from 2019 to 2021, distributed across the United States but with clusters identified in some geographic areas. Ciprofloxacin is one of the recommended first-line options for treating patients and for prophylaxis for their close contacts, who are at increased risk of acquiring the disease.

To date, no instances of prophylaxis failure associated with ciprofloxacin resistance has been reported. But because of the high mortality risk of invasive meningococcal disease and the potential for prophylaxis failure, the CDC says the threshold for changing the antibiotic prophylaxis recommendation is low.

When other antibiotics should be considered

Under the new guidelines, the CDC recommends other antibiotics be considered if, over a rolling 12-month period, two or more invasive meningococcal disease cases caused by ciprofloxacin-resistant strains are reported in a local catchment area and 20% or more of the invasive meningococcal disease cases in that area are caused by ciprofloxacin-resistant strains.

Other recommended options for prophylaxis include rifampin, ceftriaxone, and azithromycin. The CDC says local health departments have flexibility in guidance implementation.

"Ongoing monitoring for antibiotic resistance of meningococcal isolates through surveillance and health care providers' reporting of prophylaxis failures will guide future updates to prophylaxis considerations and recommendations," the authors wrote.

Trial data show efficacy, safety of first-in-class antibiotic for uncomplicated urinary tract infections

News brief

The results of two phase 3 trials that were stopped early after interim analysis showed that an investigational antibiotic gepotidacin met its goals in women with uncomplicated urinary tract infection (uUTI) were published yesterday in The Lancet.

The double-blind, non-inferiority EAGLE-2 and EAGLE-3 trials enrolled adolescent and adult women with symptoms of uUTI at 219 centers worldwide and randomly assigned them to receive oral gepotidacin or oral nitrofurantoin for 5 days, with randomization stratified by age category and history of recurrent UTIs. The primary end point was therapeutic response (success or failure) at test-of-cure (days 10 to 13), with therapeutic success defined as combined clinical success (complete symptom resolution) and microbiologic success (reduction of qualifying uropathogens).

Developed by British drugmaker GSK, gepotidacin is a first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a novel mechanism of action. GSK announced that the trials had been stopped early in November 2022.

Efficacy observed against resistant uropathogens

The interim analysis showed that gepotidacin was non-inferior in both trials and superior in EAGLE-3. In the EAGLE-2 trial, 162 (50.6%) of 320 patients in the gepotidacin group had therapeutic success, compared with 135 (47.0%) of 287 patients assigned nitrofurantoin (adjusted difference, 4.3 percentage points; 95% confidence interval [CI], –3.6 to 12.1). In EAGLE-3, 162 (58.5%) of 277 patients assigned gepotidacin achieved therapeutic success, compared with 115 (43.6%) of 264 patients in the nitrofurantoin group (adjusted difference, 14.6 percentage points; 95% CI, 6.4 to 22.8).

The most common adverse event with gepotidacin was diarrhea, which was observed in 14% of patients in EAGLE-2 and 18% in EAGLE-3.

In addition, a subgroup anaylsis found that therapeutic success rates in patients with uUTIs caused by Escherichia coli, including drug-resistant phenotypes of clinical importance, generally favored gepotidacin.

The investigators say gepotidacin's favorable safety profile and efficacy against resistant pathogens could provide "substantial benefits" to patients.

"Because of the increasing worldwide prevalence of antimicrobial resistance, these findings suggest that gepotidacin has potential as a new oral treatment for uncomplicated urinary tract infections caused by common uropathogens resistant to current therapies," they wrote.

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