Rapid, Breath Volatile Metabolite-Based Diagnosis, Species Identification, and Antibiotic Resistance Profiling in Bacterial Pneumonia

Project Summary/Abstract: A lack of diagnostics that rapidly and accurately identify bacterial pneumonia drives excessive empiric antibiotic prescribing in patients with acute respiratory infections – 30-60% of these antibiotics are unnecessary. Clinicians are under pressure to make rapid treatment decisions, usually without real-time diagnostic information that reliably differentiates patients with bacterial pneumonia from other conditions with similar clinical presentations. While time to effective treatment is a critical determinant of clinical outcome, many patients with pneumonia receive inadequate empiric antibiotics due to rising rates of antibiotic resistance in bacterial pneumonia pathogens. In contrast to bloodstream, gastrointestinal, or urinary tract infections, the lung is a particularly challenging space to access without invasive diagnostic procedures. We have established proof of concept in murine models that there are clear, bacterial species-specific breath volatile metabolite signatures in pneumonia, and that microbial breath volatile metabolites have markedly different responses to antibiotic exposure within a few hours in phenotypically susceptible vs. non-susceptible organisms. In close collaboration with a team of engineering, biostatistical, antimicrobial resistance, and regulatory experts, we will apply an advanced, portable, miniaturized gas chromatography-differential mobility spectrometry (GC-DMS) diagnostic platform to the rapid, noninvasive, point-of care diagnosis of bacterial pneumonia. We will derive breath volatile metabolite signatures that differentiate bacterial pneumonia from other clinical syndromes with a similar clinical presentation, identify the underlying bacterial species directly from metabolic fingerprints in the breath, and provide phenotypic information about antibiotic susceptibility, harnessing early differential metabolic responses to effective vs. ineffective antibiotic therapy. This assay will sharply reduce diagnostic delays in patients with pneumonia, both facilitating early administration of appropriate antibiotics and curtailing unnecessary antibiotic use.