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Quantifying respiratory and gut bacterial strain persistence to predict pneumonia treatment failure

Abstract

PROJECT SUMMARY Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are complications of hospitalization that cause significant mortality. Even when the bacterium causing HAP or VAP is recognized, antibiotic treatment for HAP and VAP often fails, resulting in adverse patient outcomes and contributing to the rise of antimicrobial resistance. Novel molecular measures of respiratory bacterial load have the potential to improve monitoring of HAP/VAP treatment response, enabling precision antibiotic treatment durations, and improving clinical outcomes. Our previous work characterizing respiratory microbiome features that define HAP and VAP, as well as the microbiome dynamics associated with antibiotic treatment, forms a foundation for the proposed study. We will (1) define respiratory bacterial load during and after HAP/VAP antibiotic treatment to predict antibiotic treatment failure from bacterial load features; (2) determine how HAP/VAP antibiotic treatment failure impacts future colonization or infection by multidrug-resistant (MDR) bacteria; and (3) define the contribution of gut-respiratory microbiome interaction and strain exchange to pneumonia treatment failure. To achieve our scientific aims, we will develop a prospective, human-subjects cohort, called REBEL (REspiratory BactErial Load), which will utilize a novel, molecular-standard approach to quantify respiratory bacterial load in the antibiotic-treatment and post-treatment periods. Longitudinal samples taken from the respiratory and gastrointestinal tracts will be characterized by both metagenomic assays and bacterial culture. We will follow subjects for 90 days after the index HAP/VAP to capture antibiotic treatment failure events and respiratory bacterial community succession, including incident MDR colonization or infection. Our findings will contribute to more effective HAP/VAP treatment protocols and will advance mechanistic understanding of how HAP/VAP treatment failure contributes to antibiotic resistance, a pressing public health threat. The proposed study will contribute to a new framework for treating bacterial HAP/VAP based on bacterial load monitoring, which accounts for both the immediate risk of antibiotic failure and long-term risks of MDR bacterial colonization and infection.

People

Funding Source

National Institutes of Health, National Institute of Allergy and Infectious Diseases

Project Period

2026-2031