A NEW follow-up study from Malawi raises concerns about the long-term impact of mass drug administration (MDA) with azithromycin on antimicrobial resistance (AMR) in Streptococcus pneumoniae, showing that resistance persists more than 3 years after MDA ended.
The cross-sectional survey was conducted in 2021, 3.5 years after completion of the MORDOR trial, which provided twice-yearly azithromycin or placebo to Malawian communities for 2 years to reduce childhood mortality. Children aged 4–9 years who had lived in either arm during the trial, and children aged 1–3 years born after it ended, were enrolled. Researchers collected nasopharyngeal swabs and used whole genome sequencing to identify macrolide resistance. Results were compared with samples from baseline, 6 months post-MDA, and isolates from a distant Malawian site without prior MDA exposure.
Among 905 children recruited, 426 S pneumoniae isolates were assessed alongside 387 historical isolates. In azithromycin-treated clusters, macrolide resistance rose from 21.7% at baseline to 31.9% at 6 months, and remained high at 32.1% at 3.5 years. Resistance also increased in placebo-treated clusters, from 21.0% at baseline to 30.9% at follow-up, suggesting regional spread. Odds ratios comparing treated and placebo groups showed no statistically significant differences at any timepoint. In contrast, resistance in the non-MDA site remained stable over time at around 16.5%. Alarmingly, macrolide resistance among post-MDA-born children in treated clusters was 36.0%. Multidrug resistance to at least three antibiotic classes was also significantly higher in both MDA arms than in the non-MDA population and was linked to mobile genetic elements.
These findings indicate that azithromycin MDA may promote durable and transmissible resistance, including in populations not directly exposed. The presence of multidrug-resistant strains with mobile resistance genes calls for urgent, sustained AMR surveillance wherever MDA strategies are in use.
Reference
Kalizang’oma A et al. Long-term effects of azithromycin mass administration to reduce childhood mortality on Streptococcus pneumoniae antimicrobial resistance: a population-based, cross-sectional, follow-up carriage survey. Lancet Infect Dis. 2025; DOI:10.1016/S1473-3099(25)00212-9.
