WHO-Recommended Antibiotics Effective in Only 25% of Neonatal Sepsis Cases in Low-Income Countries
核心洞察
The BARNARDS II study across Pakistan, Bangladesh, and Nigeria found WHO-recommended first-line antibiotics ampicillin plus gentamicin were effective against only 25% of neonatal sepsis (搜索) pathogens.
High levels of antimicrobial resistance (搜索) in low- and middle-income countries make identifying effective empirical antibiotic regimens extremely challenging for treating newborn infections.
The NeoSep1 trial is expanding to seven new countries across Africa and Asia to identify safer and more effective antibiotic combinations for neonatal sepsis (搜索) treatment.
WHO-recommended first-line antibiotics for neonatal sepsis (搜索) are effective in only one in four infections in low- and middle-income countries, according to major new research presented at ESCMID Global 2026. The findings highlight the growing impact of antimicrobial resistance (搜索) on newborn survival and challenge current global treatment guidelines.
BARNARDS II Study Reveals Limited Antibiotic Effectiveness
The BARNARDS II study, conducted by experts from the University of Oxford and an international network of collaborating institutions, examined antibiotic effectiveness across 13 tertiary neonatal units in Pakistan, Bangladesh, and Nigeria between February 2024 and October 2025. The comprehensive study included 14,259 neonates treated with empirical antibiotics for suspected sepsis.
Out of 5,012 culture-confirmed sepsis cases, 2,821 had both pathogen identification from blood cultures and available antibiotic susceptibility data. The results revealed that the WHO-recommended combination of ampicillin and gentamicin would have been active against only 25% of identified pathogens, including fungal infections.
"Most concerning were the high rates of antimicrobial resistance (搜索) identified," said Kathryn Thomson, lead author of the study from the University of Oxford. "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."
Current Treatment Practices Diverge from WHO Guidelines
The study found that only 40 neonates across the entire cohort received the WHO-recommended first-line combination of ampicillin and gentamicin. Instead, two-drug regimens were most common, with amikacin plus cefotaxime being the most frequently used combination. Initial treatment regimens varied widely and typically comprised one to three antimicrobials.
Thomson explained that deviation from WHO guidelines likely represents adaptation to local resistance patterns rather than poor adherence. "This likely represents adaptation to local resistance patterns and the challenges of applying global treatment recommendations in these environments," she noted.
NeoSep1 Trial Expands to Address Treatment Gaps
Parallel efforts to address neonatal sepsis (搜索) treatment challenges are underway through the NeoSep1 trial, led by the Global Antibiotic Research & Development Partnership (GARDP). The trial is expanding to seven new countries across Africa and Asia after establishing safe dosing for combinations of older antibiotics in newborns during its first phase.
The trial places Africa's neonatal wards at the center of global evidence generation, addressing a critical research gap. "Babies are neglected in research and development," says GARDP senior access manager Sharon Odeo. "There are very few clinical trials for newborns, and information on dosage and frequency is often limited, if it exists at all."
More than 3,000 newborns are expected to be enrolled in the expanded trial, which will include hospitals in Ghana, Kenya, Uganda, Bangladesh, India, Malaysia, Pakistan, and Vietnam, in addition to existing sites in Kenya and South Africa.
Shifting Infection Patterns Complicate Treatment
The challenge of treating neonatal sepsis (搜索) is compounded by changing patterns of infection. Between 2010 and 2023, deaths from Streptococcus pneumoniae fell by more than 54%, reflecting the impact of pneumococcal vaccines. However, deaths from Staphylococcus aureus, which is not vaccine-preventable, declined by just 1%.
As vaccine-preventable infections decline, drug-resistant pathogens are becoming a more important driver of neonatal deaths, especially in settings with limited diagnostics and delayed treatment. Despite the scale of the problem, few antibiotics developed in the past two decades are labeled for neonatal use, with only a small number including dosing information for newborns.
Need for Locally Informed Treatment Strategies
Tim Walsh, principal investigator of the BARNARDS study at the University of Oxford, emphasized that a "one-size-fits-all" approach to antibiotic guidelines is unlikely to be globally effective. "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," he said.
The NeoSep1 trial uses a personalized randomized controlled trial (PRACTical) design that accounts for differences in hospital resistance patterns, antibiotic availability and prescribing practices. "This approach allows us to compare several antibiotic regimens simultaneously," Odeo explains. "It also gives doctors the flexibility to choose treatments that are most likely to work in their own settings."
GARDP estimates that €40 million will be needed by 2028 to ensure manufacturing capacity and equitable access to effective antibiotic regimens in low- and middle-income countries.