BALANCE

Overview

BALANCE is a large, multi-country research programme led by the Ineos Oxford Institute for Antimicrobial Research (IOI), University of Oxford. The study generates robust, actionable estimates of the health and economic burden of antimicrobial resistance (AMR) in bloodstream infections (BSIs) across low-, lower-middle-, upper-middle-, and high-income countries.

Bloodstream infections, including sepsis, are life-threatening conditions requiring urgent antibiotic treatment. However, rising antimicrobial resistance is undermining the effectiveness of standard therapies. BALANCE directly compares AMR burden across diverse healthcare systems using a unified protocol, enabling meaningful global comparisons.

The ultimate aim of BALANCE is to ‘Prevent Sepsis’ and ‘Save Antibiotics.’

 

Why BALANCE Matters

Global projections estimate that by 2050, antimicrobial resistance (AMR) could be directly responsible for 1.91 million deaths annually and associated with up to 8.22 million deaths worldwide, with the highest mortality burden expected in lower-middle-income countries. Despite this growing threat, high-quality microbiology and linked clinical data remain scarce in many low-resource settings.

Most existing AMR burden estimates rely on modelling or indirect comparisons. BALANCE addresses this gap by:

• Collecting real-time clinical and microbiological data
• Measuring attributable mortality and excess length of stay
• Evaluating treatment adequacy and time to appropriate therapy
• Assessing the economic consequences of drug-resistant infections
• Comparing AMR burden across income settings using the same methodology

This approach provides precise, context-specific data to inform national and global policy.

 

Study Design

BALANCE is a multinational prospective cohort study conducted in tertiary public hospitals across:

• Low- and lower-middle-income countries (e.g. Bangladesh, Kenya, Nigeria, Pakistan)
• Upper-middle- and high-income countries (e.g. Italy, Poland, Turkey)

The study focuses on microbiologically confirmed bloodstream infections caused by priority pathogens defined by WHO, including:

• Enterobacterales
• Pseudomonas aeruginosa
• Acinetobacter species
• Staphylococcus aureus
• Enterococcus species

These organisms are analysed according to resistance profiles to measure the impact of multidrug resistance (MDR) on outcomes.

What BALANCE Measures

BALANCE integrates four core components:

1. Clinical Cohort

• Hospital incidence of microbiologically confirmed BSIs
• 30-day and in-hospital mortality
• Excess length of hospital stay
• Differences between community-onset and hospital-onset infections

2. Microbiology and Genomics

• Standardised blood culture and antimicrobial susceptibility testing
• Whole genome sequencing (WGS) of isolates
• Analysis of resistance genes, virulence factors, and clonal spread

3. Antibiotic Treatment and Stewardship

• Time to appropriate antibiotic therapy
• Adequacy of prescribed treatment
• WHO AWaRe antibiotic usage patterns
• Hospital-level antimicrobial stewardship and IPC assessments

4. Health Economics

• Out-of-pocket expenditure for antibiotics and diagnostics
• Catastrophic healthcare expenditure and impoverishment
• Socioeconomic disparities in outcomes
• Modelling cost-effectiveness of improved diagnostic capacity

 

A Unique Global Comparison

BALANCE is one of the first studies to apply the same empirical methodology across low-, middle-, and high-income countries. This allows direct comparison of:

• Incidence of drug-resistant BSIs
• Attributable mortality due to AMR
• Impact of inadequate therapy
• Role of bacterial virulence
• Influence of infection prevention and control (IPC) practices
• Socioeconomic disparities in patient outcomes

The study also addresses key methodological challenges in AMR burden estimation, including time-dependent bias and competing risks, using advanced epidemiological modelling approaches.