The World Health Organization (WHO) has set an August 14 date for a meeting of its emergency committee to discuss developments regarding a surge of mpox activity in Africa and if the situation warrants a public health emergency of international concern (PHEIC).

Some of the outbreaks in Africa involve the novel clade 1b strain that emerged in the Democratic Republic of the Congo (DRC), which has been battling a severe outbreak since 2022. Some of the DRC's neighboring countries, which hadn't confirmed any mpox cases before, are now reporting cases. Also, the parent clade 1 virus is spreading in the DRC and two other countries, and the global clade 2 mpox strain is fueling outbreaks in some of the DRC's regions and in other African countries.

Health officials are working to better understand the spread patterns and if there are differences in transmissibility and disease severity among the clades. The DRC's outbreak has been marked by sexual spread for the first time in the African region, along with household contact and suspected contributions from respiratory transmission.

For now, the countries lack vaccines and treatments to battle the virus.

Second emergency committee for mpox in 2 years

The upcoming emergency committee meeting will be the second to grapple with mpox. In June 2022, the WHO convened an emergency committee to address challenges with the international spread of the clade 2 virus and said the situation didn't at that point warrant a PHEIC. A month later, the group met again and wasn't able to reach a consensus, but WHO Director-General Tedros Adhanom Ghebreyesus, PhD, considered their advice and declared a PHEIC. 

After the group met for the fifth time in May 2023 amid a steady decline in clade 2 cases, Tedros accepted the group's recommendation that the situation no longer constituted a PHEIC and that long-term challenges could be best handled with sustained response efforts.

A new study in Open Forum Infectious Diseases analyzed the clinical features of and outcomes of pediatric and adult hospitalized COVID patients at five US sites, and found that teens were at greatest risk for severe disease among all children, and those 50 to 64 years old were at greatest risk among all adults.

The study took place from March 2020 to March 2023 and included 1,560 hospitalized COVID-19 patients. Researchers calculated adjusted odds ratios (aORs) of clinical outcomes for children versus adults, younger kids compared to teens (12 to 17 years), and for older adults compared to young adults (22 to 49 years), the authors said. 

In total the study included 885 patients ages 0 to 21 years and 675 participants ages 22 to 105 years. 

Overall, children were less commonly vaccinated compared to adults ages 21 and older (14.3% vs 34.5%), and more commonly infected with the Omicron variant (49.5% vs 26.1%). Children also had fewer comorbidities than adults did.

Children had lower odds of supplemental oxygen

Children had much lower odds of receiving supplemental oxygen (aOR, 0.57; 95% confidence interval [CI], 0.35 to 0.92) and death (aOR, 0.01; 95% CI, <0.01 to 0.58) compared to adults. However, children had increased adjusted odds of receiving high-flow oxygen (2.18; 95% CI, 1.29 to 3.67) compared to adults, which the authors explained may be because this modality is more commonly used to support ventilation in the pediatric population.

Interestingly, adults aged 50-64 years had the highest odds of requiring mechanical ventilation and ICU admission after adjusting for confounding variable.

"Overall, adolescents 12-17 years experienced the greatest disease severity among the pediatric age strata," the authors said. "Interestingly, adults aged 50-64 years had the highest odds of requiring mechanical ventilation and ICU admission after adjusting for confounding variables."

The authors said their study confirmed prior work that shows that overall children experience less severe COVID-19 disease compared to adults.

The results of the first stage of a phase 2 trial showed promising results for a CRISPR-enhanced bacteriophage cocktail targeting urinary tract infections (UTIs) caused by Escherichia coli, researchers reported late last week in The Lancet Infectious Diseases.

In the first part of the phase 2 ELIMINATE trial, researchers with North Carolina–based Locus Biosciences aimed to define a dosing regimen for LBP-EC01, a six-bacteriophage cocktail engineered with a CRISPR-Cas3 construct that targets the E coli genome, in patients with uncomplicated UTIs. 

To do so, they randomly assigned 39 patients to receive three different combinations of intraurethral and intravenous doses of the cocktail, along with daily oral doses of the antibiotic trimethoprim-sulfamethoxazole. The primary outcome was the level of LBP-EC01 in urine and blood across the treatment period. Investigators also assessed safety in enrolled patients who received at least one dose of the cocktail.

Early indication of efficacy

The results showed that a regimen consisting of 2 days of intraurethral LBP-EC01 (2 x 10¹² plaque forming units [PFUs]) and 3 days of concurrent intravenous LBP-EC01 (1 x 10¹⁰ PFUs) plus oral trimethoprim-sulfamethoxazole twice daily was well tolerated and showed high and consistent bioavailability in urine and blood and a promising pharmacodynamic effect. Forty-four adverse events were observed in 18 patients (46%) in the safety population, but no serious adverse events were reported.

The results also provided an early indication of efficacy. A rapid reduction in E coli in urine was observed within 4 hours of treatment and maintained at the day 10 test-of-cure evaluation in 16 patients, all of whom had complete resolution of UTI symptoms by day 10.

"These results, although preliminary, suggest that the natural propensity for bacteriophages and bacteria to establish an equilibrium can be disrupted, in favour of bacterial eradication, through selecting the appropriate indication (ie, UTI) and dosing regimens and routes of administration that enable high direct exposure and using cocktails of bacteriophages, including ones that are genetically enhanced," the investigators wrote.

The dosing regimen will be carried through to the second part of the trial, which will investigate its efficacy in a larger population.

A retrospective analysis of data on US hospital patients with infections caused by Enterobacterales and Pseudomonas aeruginosa found that inadequate empiric therapy (IET) and delayed use of newer antibiotics was associated with significantly worse outcomes, researchers reported late last week in BMC Infectious Diseases.

Using data from the Becton Dickinson (BD) Research Insights Database, researchers with BD and drugmaker Abbvie analyzed data on hospitalized adults with facility-reported antibiotic susceptibility results at 161 US facilities from 2018 through 2022. They defined IET as antibiotic therapy prescribed within 48 hours prior to culture collection until first susceptibility results that either did not cover the pathogen or to which the pathogen was found non-susceptible. Newer antibiotics included ceftazidime-avibactam, ceftolozane-tazobactam, cefiderocol, meropenem-vaborbactam, eravacycline, and imipenem-cilcastatin-relebactam.

Findings highlight need for faster susceptibility results

Among 229,320 Enterobacterales and 36,027 P aeruginosa susceptibility results, 1.7% and 16.8% were carbapenem non-susceptible (carb-NS), respectively. In patients with Enterobacterales infections, median time to first susceptibility result was longer for carb-NS than for carbapenem-susceptible infections (64 hours vs 48 hours), and IET was prescribed in 24% of hospital admissions. In multivariate analysis, IET was associated with significantly higher mortality (odds ratio [OR], 1.29; 95% confidence interval [CI], 1.16 to 1.43) and longer hospital stays (14.8 vs 13.3 days).

In P aeruginosa patients, IET was prescribed in 46.1% of admissions. Although mortality was numerically higher with IET, the difference was not statistically significant (OR, 1.17; 95% CI, 0.97 to 1.41), and there was no difference in hospital length of stay (LOS; 12.7 days for both).

Newer antibiotic therapy was prescribed for 703 Enterobacterales patients and 603 P aeruginosa admissions. Delayed start to newer antibacterial therapy was associated with significantly greater hospital mortality and significantly longer post-culture LOS for both groups.

"In conclusion, our study demonstrates that obtaining more rapid antibacterial susceptibility results may improve overall adequacy of empiric therapy and facilitate appropriate and timely use of newer antibacterials," the study authors wrote. "Given the importance of rapid diagnostics, the integration of key diagnostic tests with antibacterial stewardship programs should be considered."