A microbiota-based live biotherapeutic for treating recurrent Clostridioides difficile infection (rCDI) remained effective after subsequent antibiotic exposure, researchers reported this week in Open Forum Infectious Diseases.

In a post-hoc analysis of a phase 2 trial evaluating the safety, efficacy, and durability of Rebyota fecal microbiota transplantation for preventing rCDI, the researchers evaluated patients who received non-CDI antibiotics for up to 2 years after Rebyota administration. Although Rebyota has been found to be highly effective in preventing rCDI and was approved by the US Food and Drug Administration in December 2022, the researchers wanted to assess the durability of the treatment response, particularly in patients subsequently exposed to antibiotics, which can disrupt the gut microbiome and increase the risk of rCDI. They looked specifically at non-CDI antibiotics, because any recurrence of CDI would require antibiotic treatment.

Treatment response was defined as the absence of CDI diarrhea needing retreatment as of the last evaluable time point (8 weeks, 6 months, 1 year, or 2 years) after Rebyota administration.

Durable response

Of the 149 participants in the trial, 43 received non-CDI antibiotics after Rebyota administration over a 2-year period. Across all evaluable time points, 37 of 43 (86%) had treatment response regardless of when non-CDI antibiotic exposure occurred, with treatment response rates ranging from 83% to 96% at the various time points. 

Among participants with treatment response, success was sustained for a median of 470 days from the first initial non-CDI antibiotic use. Of the six participants who experienced rCDI, 5 received a high-risk antibiotic. 

Although the study was limited by lack of a control group and other factors, the researchers say the findings provide evidence that Reboyota offers durable protection after antibiotic exposure in a real-world population.

"Irrespective of the inherent limitations of this analysis, these results suggest RBL [Rebyota] may restore the gut microbiota to a sufficient threshold protective against rCDI for many patients despite subsequent non-CDI antibiotic use," they wrote.

Analysis of gonorrhea samples in Cambodia found sustained transmission of ceftriaxone-resistant strains and a threefold jump in extensively drug-resistant (XDR) isolates, researchers reported this week in Emerging Infectious Diseases.

For the study, researchers with Cambodia's National Center for HIV/AIDS, Dermatology, and Sexually Transmitted Diseases and the World Health Organization (WHO) performed antimicrobial susceptibility tests and genomic analysis on 72 Neisseria gonorrhoeae isolates collected in 2023 through the WHO's Enhanced Gonococcal Antimicrobial Surveillance Program (EGASP). Under EGASP protocols, public health alerts are sent upon identification of strains approaching resistance.

A 'substantial threat' for gonorrhea control

EGASP alert minimum inhibitory concentrations (MICs) for ceftriaxone and cefixime—two first-line treatment options for gonorrhea—were detected in 22 (31%) of 72 isolates, a proportion similar to that reported in 2022 (38%). But 9 isolates (12.5%) had the XDR phenotype, which combines ceftriaxone resistance and high-level azithromycin resistance, and all belonged to the same sequence type (ST-16406). That's up from 4% in 2022. In addition, the percentage of isolates with high resistance to ciprofloxacin and penicillin remained high (82% to 97%).

Genomic analysis of 54 isolates with ceftriaxone alert MICS in 2022 and 2023 found that 50 carried the same resistance mutation (the penA-60.001 allele), and 4 harbored recently described or novel mutations. Furthermore, sequences from only 8 isolates clustered with a widely disseminated, ceftriaxone-resistant clone (FC428).

"Our data provide further evidence for sustained transmission of N. gonorrhoeae strains with elevated MICs for ceftriaxone and increased expansion of isolates with elevated MICs to ceftriaxone and azithromycin that genomically cluster with the XDR N. gonorrhoeae phenotype," the study authors wrote. "Furthermore, strains with elevated MICs for ceftriaxone continue to emerge across different phylogenetic backbones separate from the previously described FC428 clone, confirming concerns that biological fitness is not compromised by that allele and consequently poses a substantial threat for gonococcal disease control."

They add that the findings, combined with recent reports of rising ceftriaxone resistance in China, highlight the need to prioritize gonococcal antimicrobial resistance surveillance across the Asia-Pacific region.

For the first half of 2024, dengue cases in the Americas region have already surpassed yearly maximums, and cases have already doubled those of 2023, the Pan American Health Organization (PAHO) said this week in its latest epidemiologic update.

So far more than 9.3 million cases have been reported by 43 countries and territories. About half were lab confirmed. Of the total, 9,592 were severe and 4,529 were fatal. Six countries accounted for nearly all the deaths: mostly Brazil, followed by Argentina, Peru, Paraguay, Colombia, and Ecuador.

Compared to both 2023 and 5-year case averages, cases were up most sharply in the Caribbean region, followed by the Southern Cone, Central America and Mexico, and Andean-region countries. 

All 4 serotypes circulating

All four dengue virus serotypes have been circulating in the Americas, with levels varying by country. All four are circulating simultaneously in Brazil, Costa Rica, Guatemala, Honduras, Mexico, and Panama.

The agency urged countries to continue their surveillance, diagnosis, treatment, and vector control activities. PAHO also said clustering of cases is also common with diseases including dengue, chikungunya, and Zika. "Efforts should be made to analyze the spatial distribution of cases to enable a rapid response at the local level in the most affected areas," it said. "Information from the hotspots of the three diseases should be targeted for intensive vector control."

Today in Morbidity and Mortality Weekly Report, authors describe the distribution of the antiviral drug tecovirimat (Tpoxx) in Los Angeles County during the 2022-23 global mpox outbreak, which was spread largely among men who have sex with men.

Los Angeles was one of the epicenters of the mpox outbreak in the United States, and public health officials quickly developed a hub-and-spoke distribution model to deliver the antivirals to those who had been exposed to the virus, consisting of 44 hub facilities serving 456 satellite sites across the county, with two-thirds being clinics or pharmacies. 

This strategy was built on the COVID-19 vaccine rollout.

"This strategy was built on the COVID-19 vaccine rollout, for which clinics and pharmacies were crucial to vaccine distribution networks," the authors said. 

Median time to treatment was 2 days 

Thirty-nine percent of all California mpox cases occurred in Los Angeles County, the most populous county in the state. By January 31, 2023, 2,281 patients with mpox were reported in the county, and approximately one-third (735; 32%) had been treated with tecovirimat.

"120 (16%) patients who received tecovirimat were treated at pharmacies, 227 (31%) at hospitals, and 388 (53%) at community clinics," the authors wrote. The median interval from specimen collection to treatment was 2 days, and the average patient age was 38.

"Overall, the distribution strategy was effective and sufficient to meet increasing needs. Similar strategies might benefit tecovirimat distribution in different jurisdictions as would other prepositioned therapeutics for mpox or future emerging infections," the authors concluded.