A major international study reveals that World Health Organization-recommended first-line antibiotics are effective in only one in four neonatal sepsis infections in low- and middle-income countries, underscoring the growing threat of antimicrobial resistance.
New research presented at ESCMID Global 2026 highlights a critical gap in the effectiveness of current global treatment guidelines for neonatal sepsis, a life-threatening condition that remains a leading cause of newborn mortality worldwide.
The study, led by researchers from University of Oxford and conducted across 13 neonatal units in Pakistan, Bangladesh, and Nigeria, evaluated over 14,000 infants treated for suspected sepsis between 2024 and 2025. Findings from the BARNARDS II study show that the WHO-recommended first-line antibiotic regimen of ampicillin plus gentamicin, would have been effective against only 25% of identified pathogens.
Researchers observed high levels of antimicrobial resistance (AMR), complicating efforts to deliver timely and effective empirical treatment. Despite global guidelines, clinicians often used alternative antibiotic combinations, reflecting real-world adaptation to local resistance patterns.
Out of 2,821 cases with full microbiological data, only 36.8% of neonates received appropriate empirical therapy. Those who received inappropriate treatment experienced significantly higher mortality rates, although this link weakened after adjusting for clinical factors such as gestational age.
WHO-recommended first-line antibiotics for neonatal sepsis were effective in only 25% of cases studied in LMIC hospital settings.
High antimicrobial resistance is limiting the effectiveness of standard treatments and driving clinicians to adapt therapies locally.
Tailored, locally informed treatment strategies and improved diagnostics are essential to improve neonatal survival rates.
“Most concerning were the high rates of antimicrobial resistance identified,” lead author Kathryn Thomson, PhD, University of Oxford, said in a statement. “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.”
The findings suggest that global “one-size-fits-all” antibiotic recommendations may not be suitable for diverse healthcare settings, particularly in regions with high AMR burdens.
Reflecting on the study’s implications, principal investigator of the BARNARDS study, Professor Tim Walsh, said, “Our results show that a one-size-fits-all approach to empirical antibiotic guidelines is unlikely to be effective globally. Even across the countries included in this study, we observed important differences in both the pathogens responsible for infection and their resistance profiles.”
