Trial finds no difference between continuous, intermittent meropenem for sepsis patients

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A randomized controlled trial found that continuous administration of the antibiotic meropenem does not improve clinical outcomes in critically ill sepsis patients compared with intermittent administration, researchers reported today in JAMA.

Meropenem is typically administered intermittently to treat several types of infections in critically ill patients, but several systematic reviews and meta-analyses show that continuous administration may decrease mortality in sepsis patients and reduce the emergence of antibiotic resistance. To test this hypothesis, investigators enrolled critically ill patients with sepsis or septic shock at 26 hospitals in four countries (Croatia, Italy, Kazakhstan, and Russia) and randomly assigned them 1:1 to receive an equal dose of meropenem by either continuous administration or intermittent administration.

The primary outcome was a composite of all-cause mortality, and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were four secondary outcomes, including all-cause mortality at day 90.

A total of 607 patients (mean age, 64 years; 33% female) were included in both the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days and the median duration of meropenem therapy was 11 days.

The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96; 95% confidence interval [CI], 0.81 to 1.13). No adverse events were reported. At day 90, mortality was 42% in both groups. No statistically significant differences were found for the other secondary outcomes.

In an accompanying editorial, experts from Harvard Medical School say that because there was no evidence of harm from continuous administration of meropenem, it's unclear whether the trial results will influence clinical guidelines.

"Notwithstanding the negative results of this trial, guidelines and clinical practice may continue to favor prolonged dosing of β-lactam antibiotics when circumstances allow given the ongoing possibility of benefit and absence of harm," they wrote. "Meanwhile, there remains an urgent need to identify new interventions to realize the shared aspiration to reduce sepsis mortality and antimicrobial resistance."

Spanish study shows efficacy of Jynneos mpox vaccine is 89%

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Stephanie Soucheray, MA

When used as post-exposure prevention (PEP) of mpox, the vaccine Jynneos had an adjusted vaccine effectiveness (VE) of 88.8%, and vaccination can be protective against the virus up to 7 weeks following exposure, according to a study published yesterday in Eurosurveillance.

The real-world prospective cohort study to assess VE of one vaccine dose given as PEP took place in Madrid from May 17 to August 15, 2022, among close contacts of confirmed mpox cases. The vaccine was offered up to 14 days post exposure, preferentially in the first 4 days, the authors said.

Overall, the VE was 88.8% (95% confidence interval [CI], 76.0 to 94.7). Results were divided among close contacts who shared a living space with the index patient, and those who did not. VE was 93.6% for non-cohabitants and 88.6% for cohabitants.

"We found that breakthrough infections did not exhibit severe symptoms (none required hospitalization)," the authors said. "Furthermore, there were fewer symptoms, a reduction in general symptoms of at least 18.1% and a reduction in polysymptomatic disease of at least 26.7% in vaccinated cases compared with unvaccinated cases.”

The authors of the study said this real-world data supports PEP for controlling mpox outbreaks.

Quick takes: Peruvian dengue surge, polio in Africa, mpox cases in Colorado

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Lisa Schnirring

Peru is battling a record dengue outbreak in the wake of cyclone rains in the country's north in April and May, which fueled an increase in mosquito populations. So far, Peru has reported more than 146,000 cases and 248 deaths, and the struggle to control the outbreak has led to the resignation of the country's health minister, the BBC reported today. The country's president declared a state of emergency last week, and health officials fear a worsening situation with the El Nino weather pattern expected to produce more heavy rain later this year.
Four African countries reported more polio cases this week, all involving vaccine-derived types, the Global Polio Eradication Initiative (GPEI) said yesterday in its latest weekly update. Ivory Coast reported a circulating vaccine-derived poliovirus type 2 (cVDPV2) case from Bounkani, its second of the year. The Democratic Republic of Congo (DRC) reported 6 more cVDPV2 cases, as well as 10 more infections from circulating vaccine-derived poliovirus type 1 (cVDPV1). Mali reported its first two cVDPV2 cases of the year, and Nigeria reported 4 more cases involving the strain, all from Zamfara, bringing its 2023 total to 10.
Colorado health officials have reported three new mpox cases, all from the Denver area, which prompted new public health reminders about the availability of vaccines, testing, and treatment. The Colorado Department of Public Health and Environment said of the three cases confirmed by Denver's public health department, two involved people who were fully vaccinated with two doses of the Jynneos vaccine.