Streptococcus pneumoniae remains a major cause of child morbidity and mortality in sub-Saharan Africa, with increasing macrolide resistance mediated by erm(B) and mef(A/E/I) . Integrating phenotypic and sequencing-based approaches may improve antimicrobial resistance surveillance accuracy. This study assessed nasopharyngeal carriage and macrolide resistance of S. pneumoniae among young infants in Sierra Leone (November 2022–February 2023), nested within the ICARIA trial (NCT04235816) which evaluated azithromycin for child mortality reduction. Infants aged 6–10 weeks presenting for Penta-1 immunization before trial recruitment were enrolled. Two nasopharyngeal swabs were collected per infant. S. pneumoniae was detected by lytA PCR, azithromycin minimal inhibitory concentrations (MICs) were determined by E-test, and erm(B) and mef(A/E) were identified by PCR in isolates. A subset of paired samples underwent targeted amplicon sequencing for microbiome and resistome profiling. Carriage prevalence was 17.3% (162/936; 95% CI: 14.9–19.9%), with 45.7% (74/162) of isolates resistant to azithromycin (MIC ≥ 2 μg/mL). High-level resistance (MIC ≥ 64 μg/mL) was mainly mediated by erm(B) alone (53.8%) or in combination with mef(A/E) (38.5%), whereas all 22 moderately resistant isolates (MIC 2–48 μg/mL) carried mef(A/E) only. Among susceptible isolates, 3.8% (2/52) harbored mef(A/E) despite low MICs . Microbiome sequencing showed 96% concordance with lytA PCR for S. pneumoniae detection. Normalized resistome read counts for erm(B) and mef(A/E) were significantly higher in PCR-positive samples ( p = 1.98 × 10 −9 and p = 8.14 × 10 −7 ). These findings provide the first estimates of nasopharyngeal S. pneumoniae carriage and macrolide resistance among infants in Sierra Leone, revealing a high prevalence of resistance. The results underscore the need to strengthen antibiotic stewardship, particularly in child survival programs with azithromycin. Large and longitudinal studies are also needed. Clinical Trial Registration : ClinicalTrials.gov , NCT04235816 .
Chen et al. (Fri,) studied this question.