Azithromycin with or without cefixime for suspected or culture-confirmed uncomplicated typhoid fever in Nepal, Bangladesh, and Pakistan (ACT-South Asia): a double-blind, parallel-group, randomised, placebo-controlled, phase 4 trial
The Lancet Infectious Diseases·
- DOI
- 10.1016/s1473-3099(26)00358-0
- PMID
- 42624818
- PMCID
- —
- OpenAlex
- W7203820018
- Study type
- Journal article
- Publisher
- Elsevier BV
- Article type
- journal-article
- Integrity
- current
Why this research matters now
The findings support the WHO recommendation of oral azithromycin monotherapy for uncomplicated typhoid fever and provide no evidence to justify adding cefixime, which has important antimicrobial stewardship implications given concerns about dual-drug resistance emergence.
Structured evidence summary
Research question
The trial assessed whether combining azithromycin with cefixime reduces treatment failure in uncomplicated typhoid fever compared to azithromycin alone.
Study design
This was a double-blind, parallel-group, randomized, placebo-controlled phase 4 trial conducted across three South Asian countries. Participants were randomly assigned 1:1 to receive either azithromycin plus cefixime or azithromycin plus placebo for seven days, with treatment allocation concealed from all personnel and participants.
Population and setting
The study enrolled 1847 adults and children aged 2-65 years with blood culture-confirmed or clinically suspected uncomplicated typhoid fever from emergency and outpatient clinics in Nepal, Bangladesh, and Pakistan. Participants presented with acute undifferentiated febrile illness lasting 3-14 days and elevated C-reactive protein, with negative tests for dengue, scrub typhus, malaria, and COVID-19.
Main findings
Treatment failure occurred in 5.1% of participants in both the azithromycin-cefixime group and the azithromycin-placebo group, with no significant difference between arms. Among culture-confirmed cases, failure rates were 11.2% with combination therapy versus 16.0% with azithromycin alone, but this difference was not statistically significant. Adverse event rates were comparable between groups at 16% each.
Public-health relevance
The findings support the WHO recommendation of oral azithromycin monotherapy for uncomplicated typhoid fever and provide no evidence to justify adding cefixime, which has important antimicrobial stewardship implications given concerns about dual-drug resistance emergence.
Important limitations
This summary relies on the supplied single-article abstract and metadata. Full interpretation of trial limitations, including power calculations, adherence rates, and subgroup analyses, requires review of the complete published manuscript.
GIDS interpretation
The article is indexed under typhoid fever treatment in three endemic South Asian countries and is discoverable through disease and geographic classifiers. It addresses a clinical management question rather than documenting surveillance trends or outbreak characteristics.
Related GIDS surveillance
Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.
Evidence relationships
This article has 8 auditable classifier relationships to diseases, places, topics, and study design.