Infectious Diseases

Pediatric azithromycin MDA increases gut macrolide resistance without clear nasopharyngeal effect

In AVENIR, 3,000 Niger communities were cluster-randomized to semiannual azithromycin for 1–59-month-olds, infants only, or placebo for 2 years. Among 150 sampled communities, azithromycin to 1–59-month-olds increased gut macrolide resistance by 16% vs placebo and 13% vs infant-targeting. Infant-targeted azithromycin showed only a small, statistically non-significant gut resistance increase compared with placebo. No significant differences in macrolide resistance were found in nasopharyngeal samples between arms. These results underscore age-targeting effects on intestinal resistance and support built-in AMR surveillance for mortality-reduction MDA programs. 1

Empiric azithromycin in COVID-19 remodels URT resistome without anti-inflammatory payoff

A multicenter prospective cohort followed 1,164 hospitalized COVID-19 patients with longitudinal nasal metatranscriptomics and systemic immune profiling. Patients receiving azithromycin (n=366) had altered upper respiratory microbiome composition and increased expression of MLS resistance genes. Resistome changes emerged after one day of exposure, persisted beyond a week, and involved commensals and potential pathogens. There were no detectable differences in host inflammatory gene expression in blood or airways between azithromycin-treated and control groups. Findings argue against empiric azithromycin as an anti-inflammatory adjunct in viral pneumonia and highlight added resistance pressure. 2

Whole-genome sequencing reliably predicts isoniazid resistance in New York MTBC isolates

This 6-year, two-phase study analyzed 3,696 Mycobacterium tuberculosis complex strains to evaluate WGS-based prediction of isoniazid resistance. In 1,767 isolates with paired phenotypic testing, WGS achieved 90.3% sensitivity and 99.8% specificity for isoniazid resistance. The negative predictive value for phenotypic isoniazid susceptibility was 98.8%, supporting WGS as a strong rule-out tool. A WGS-guided testing algorithm applied to 1,929 subsequent strains reduced phenotypic DST use, cost, and turnaround time. Most phenotypic isoniazid resistance mapped to known resistance loci, reinforcing WGS integration into TB program diagnostics. 3

Plasma Mtb ccfDNA ddPCR detects incipient and extrapulmonary TB in high-risk contacts

Investigators evaluated a dual-target ddPCR assay for plasma Mtb cell-free DNA (IS6110, IS1081) in high-risk household contacts and diagnostically challenging TB. The assay detected Mtb DNA in most asymptomatic and unconfirmed or possible TB, including extrapulmonary disease. Among 46 household contacts who progressed, Mtb ccfDNA was detected in 79% up to six months before TB diagnosis, with high specificity. Detection rates at 12–18 months before disease were lower, suggesting rising ccfDNA as clinical TB approaches. The test achieved 100% sensitivity for extrapulmonary TB within six months of diagnosis, pending confirmation in larger cohorts. 4