Universal antibiotic for young children reduces mortality in Africa

The AVENIR randomized trial found that community-wide distribution of azithromycin to both infants and children in Niger was effective in preventing deaths, but areas where only infants were given the drug did not see a reduction in mortality.

Large-scale, twice-yearly distribution of antibiotics to infants and children aged 1 to 59 months reduced mortality by 14% (95% CI 7 to 22, PCompared to placebo, the risk of death was reduced to less than 0.001 across the entire age range, including a 17% reduction in children 1 to 11 months of age and a 13% reduction in children 12 to 59 months of age.

But azithromycin, which was given only to infants aged 1 to 11 months, did not significantly protect infants or older children, reported Thomas Rietman, MD, PhD, of the University of California, San Francisco, and colleagues. New England Journal of Medicine.

“The modest and statistically non-significant effect when treating only infants aged 1 to 11 months is not in itself surprising,” Rietman said. Medpage Today“we, [older children] It had a dramatic effect on infant mortality rates between 1 and 11 months of age.”

The findings contradict the World Health Organization. Conditional Recommendation In sub-Saharan Africa, where infant mortality rates are high, mass distribution will be restricted to infants aged 1 to 11 months.

No studies have been done to limit azithromycin treatment to infants aged 1 to 11 months, but this group would benefit most. 2018 MORDOR TRIALThis study found that community-wide distribution of twice-yearly azithromycin to infants aged 1 to 59 months in sub-Saharan Africa reduced all-cause mortality by 25% among infants aged 1 to 11 months and by 13.5% among infants up to 59 months of age.

The exact mechanism is Community Broadcasting It is not known whether azithromycin reduces mortality, but it has Chlamydia trachomatisIt provides short-term protection against malaria and is also effective against intestinal and lower respiratory tract infections, all of which are leading causes of death in sub-Saharan Africa.

Rietman and his colleagues hypothesized that high doses of azithromycin might not only treat individual infections but also reduce the population burden of the pathogen. “We were surprised by how strongly this hypothesis showed up in our results,” Rietman said.

“These results call into question most current recommendations regarding mass distribution of azithromycin, with the exception of concerns about increasing antibiotic resistance,” wrote Catherine Maitland, MD, of Imperial College London, and A. Sarah Walker, PhD, of University College London. Accompanying editorial.

The editorialists noted that the AVENIR antibiotic resistance data have not yet been published. The MORDOR study found that determinants of resistance in the azithromycin-treated community were approximately 7.5x They were more likely to develop pulmonary embolism than those in the placebo group. Continuing learning There was some evidence that efficacy continued even after three years.

The analysis included data from 1,229 rural communities randomly selected to distribute azithromycin twice a year for two years to infants aged 1 to 59 months, 751 communities randomly selected to give the antibiotic to infants aged 1 to 11 months and a placebo to infants aged 12 to 59 months, and 929 communities randomly selected to give a placebo to both age groups.

Of 382,582 children aged 1 to 59 months who participated in the study, 5,503 deaths occurred. Among infants aged 1 to 11 months, the mortality rate was 22.3 per 1,000 person-years in areas that received azithromycin compared with 23.9 per 1,000 person-years in areas that received placebo. For all children aged 1 month to 59 months, the mortality rate was 11.9 per 1,000 person-years in areas that received azithromycin compared with 13.9 per 1,000 person-years in areas that received placebo.

One serious adverse event occurred in the pediatric azithromycin group, one in the infant azithromycin group, and three in the placebo group. No adverse events were attributable to azithromycin.

The authors acknowledge that the study has several limitations: Overall mortality was lower than expected, and patients were only monitored for two years, limiting conclusions about the long-term effectiveness of azithromycin. Also, the trial was limited to two regions of Niger, meaning the results may not be generalizable to other areas.