WHO-RECOMMENDED first-line antibiotics for neonatal sepsis are likely to be effective in only one in four infections in low- and middle-income countries (LMIC), according to new findings presented at ESCMID Global 2026 on 21st April.1
Results of the major multi-country study highlight the growing impact of antimicrobial resistance.
Neonatal Sepsis
Neonatal sepsis is a life-threatening condition that occurs within the first month of life and remains a leading global cause of newborn mortality.2
Currently, WHO recommends ampicillin plus gentamicin as first-line empirical antibiotic therapy.3 However, these recommendations are reportedly largely based on data from high-income settings.
The BARNARDS II Study
Experts from the University of Oxford and an international network of collaborating hospitals and research institutions conducted the BARNARDS II study across 13 tertiary neonatal units in Pakistan, Bangladesh, and Nigeria between February 2024 and October 2025.
The study included 14,259 neonates treated with empirical antibiotics for suspected sepsis, with initial treatment regimens varying widely and typically comprising one to three microbials.
Two-drug regimens were most common: most frequently amikacin plus cefotaxime.
Only 40 neonates across the entire cohort received the WHO-recommended first-line combination of ampicillin and gentamicin.
Out of 5,012 culture-confirmed sepsis cases, 2,821 had both pathogen identification from blood cultures and available antibiotic susceptibility data.
High Levels of AMR
High levels of AMR were observed and the WHO-recommended combination would have been active against only 25% of identified pathogens (including fungal).
Kathryn Thomson, lead author of the study, University of Oxford, Oxford, UK, said: “Most concerning were the high rates of antimicrobial resistance identified.
“The substantial AMR burden makes identifying consistently effective empirical antibiotic regimens extremely challenging.
“In these settings, ampicillin and gentamicin would have provided limited coverage against the locally prevalent, highly resistant pathogens.”
Improving Neonatal Care
She explained that, rather than reflecting poor adherence to WHO guidelines, deviation due to limited expected effectiveness is clinically understandable.
Thomson continued: “This likely represents adaptation to local resistance patterns and the challenges of applying global treatment recommendations in these environments.”
Tim Walsh, principal investigator of the BARNARDS study, University of Oxford, Oxford, UK, said that a “one-size-fits-all” approach to the relevant antibiotic guidelines is unlikely to be globally effective.
He added: “Improving neonatal outcomes will ultimately require use of locally informed empirical treatment strategies, enhanced diagnostics, continued AMR surveillance, antimicrobial stewardship and sustainable access to effective antibiotics, supported by long-term policy commitment and investment.”
References
1 Thomson K et al. Appropriateness of empirical antibiotic therapy and mortality in neonatal sepsis across LMIC hospitals. 2026. Oral presentation. ESCMID Global 2026, 17-21 April, 2026.
2 Mahmoud HAH et al. Insight into neonatal sepsis: an overview. Cureus. 2023;DOI:10.7759/cureus.45530.
3 Obiero CW et al. Empiric treatment of neonatal sepsis in developing countries. Pediatr Infect Dis J. 2026;34(6):659-661.
Featured image: Nenov Brothers on Adobe Stock
