The Effect of Widespread Distribution of Azithromycin on Childhood Mortality and Antibiotic Resistance in Sub-Saharan Africa: A Systematic Review and Meta-Analysis
1
Science and Mathematics, University of Washington Tacoma, Tacoma, United States
Popul. Med. 2026;8(Supplement Supplement 1):
ABSTRACT
BACKGROUND:
Evidence from several randomized controlled trials (RCTs) has suggested that widespread administration of azithromycin in communities could be a useful public health intervention in reducing childhood mortality in countries with high infectious disease burdens. However, the extent of the benefit of the intervention in the context of possible increases in antibiotic resistance remains debatable. This meta-analysis synthesized the existing evidence on the impact of the widespread distribution of azithromycin administration on child mortality and antibiotic resistance.
METHODS:
We searched Cochrane CENTRAL, PubMed, Scopus, CINAHL, Google Scholar, and preprint archives for randomized controlled trials (RCTs) that assessed childhood mortality and antibiotic resistance outcomes following either widespread individual or mass azithromycin administration in children. Effect estimates (incidence rate ratios and odds ratios) were synthesized using a bias-adjusted inverse heterogeneity model, with subgroup analyses performed based on age group, country and treatment regimens. Heterogeneity was evaluated using the I² statistic, and publication bias using funnel and Doi plots.
RESULTS:
Twenty-seven RCTs met the inclusion criteria. In overall synthesis, the widespread use of azithromycin showed no benefit, except in infants, where mass administration of the drug reduced mortality by 22% (IRR 0.78, 95%CI 0.57–1.00; I² = 86.4%), with variation across countries. Further analysis showed that the intervention was effective only in infants from countries with high underlying childhood mortality rates. Synthesis of data from ten RCTs showed that mass administration of azithromycin increased the odds of macrolide resistance by almost 2-fold (OR 1.83, 95%CI 1.04–3.23; I² = 89.0%).
CONCLUSIONS:
This analysis suggests that widespread azithromycin administration in children may have minimal benefit in reducing mortality except in infants in high-mortality regions, while concurrently increasing the odds of antibiotic resistance. The limited benefit and higher odds of antibiotic resistance suggest a need to consider stopping this intervention and recommending other well-established public health strategies.
Evidence from several randomized controlled trials (RCTs) has suggested that widespread administration of azithromycin in communities could be a useful public health intervention in reducing childhood mortality in countries with high infectious disease burdens. However, the extent of the benefit of the intervention in the context of possible increases in antibiotic resistance remains debatable. This meta-analysis synthesized the existing evidence on the impact of the widespread distribution of azithromycin administration on child mortality and antibiotic resistance.
METHODS:
We searched Cochrane CENTRAL, PubMed, Scopus, CINAHL, Google Scholar, and preprint archives for randomized controlled trials (RCTs) that assessed childhood mortality and antibiotic resistance outcomes following either widespread individual or mass azithromycin administration in children. Effect estimates (incidence rate ratios and odds ratios) were synthesized using a bias-adjusted inverse heterogeneity model, with subgroup analyses performed based on age group, country and treatment regimens. Heterogeneity was evaluated using the I² statistic, and publication bias using funnel and Doi plots.
RESULTS:
Twenty-seven RCTs met the inclusion criteria. In overall synthesis, the widespread use of azithromycin showed no benefit, except in infants, where mass administration of the drug reduced mortality by 22% (IRR 0.78, 95%CI 0.57–1.00; I² = 86.4%), with variation across countries. Further analysis showed that the intervention was effective only in infants from countries with high underlying childhood mortality rates. Synthesis of data from ten RCTs showed that mass administration of azithromycin increased the odds of macrolide resistance by almost 2-fold (OR 1.83, 95%CI 1.04–3.23; I² = 89.0%).
CONCLUSIONS:
This analysis suggests that widespread azithromycin administration in children may have minimal benefit in reducing mortality except in infants in high-mortality regions, while concurrently increasing the odds of antibiotic resistance. The limited benefit and higher odds of antibiotic resistance suggest a need to consider stopping this intervention and recommending other well-established public health strategies.
| eISSN: | 2654-1459 |
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