Data Challenge: Global Surveillance of Resistance to Ampicillin–Gentamicin and Ceftriaxone in Children with Severe Infections: Evidence to Inform WHO AWaRe Guidelines

Antimicrobial resistance (AMR) poses a critical global health threat, particularly impacting empiric therapy for severe infections including respiratory and bloodstream infections. WHO recommends ampicillin-gentamicin combinations or ceftriaxone as first-line empiric treatments for severe illnesses. However, increasing global resistance threatens their effectiveness, compromising treatment outcomes and patient safety. Studies reveal alarming resistance rates among paediatric pathogens: Escherichia coli (ampicillin resistance ranges from 50–93%, gentamicin resistance ranges from 13–56%), Klebsiella pneumoniae (universal resistance to ampicillin, gentamicin resistance ranges from 60–91%, and ceftriaxone resistance has risen to 91% in some areas). The rates of co-resistance data, however, are rarely reported.
This study will assess and map global resistance rates to ampicillin-gentamicin combination therapy and ceftriaxone, utilizing surveillance data from ATLAS (Pfizer), KEYSTONE (Paratek), Innoviva Specialty Therapeutics, and GEARS (Venatorx) databases. Together with IHME mortality estimates and global health equity indicators, resistance patterns, associated mortality burden and stewardship infrastructure will be analysed regionally and temporally, identifying hotspots and trends to inform empiric treatment recommendations.
A mixed-methods approach will be utilized, combining resistance surveillance data with existing literature on the impact of syndrome-specific antimicrobial resistance to evaluate clinical implications. Advanced statistical analyses will assess pooled resistance prevalence, genotype-phenotype correlations, time-series modelling of resistance patterns, identifying key drivers of resistance variability. We will develop a region-specific index as a composite metric integrating resistance rates to ampicillin, gentamicin and ceftriaxone to support stewardship planning prioritization. Additionally, we will explore alternative empiric regimens and stewardship strategies in high resistance contexts, with attention to clinical applicability and implications for resource-limited settings.
Findings will identify areas where WHO-recommended empiric regimens require re-evaluation and regions with high resistance and low diagnostics or stewardship infrastructure. This work aims not only to maintain antibiotic efficacy but also to strengthen global stewardship efforts, ultimately improving patient outcomes and reducing the AMR burden.