Pervasive Presence of Detectable Pathogens in the Lung Lower Airway Microbiome Correlates With Ventilator-associated Pneumonia Microbiologic Diagnosis for Species-specific Pathogens

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Abstract RATIONALEVentilator-associated pneumonia (VAP) is an avoidable occurrence in critically ill patients. VAP diagnosis is clinical and does not require identification of a pathogen in culture. We hypothesized that the lower airway microbiome would correlate with clinical sputum cultures in a cohort of critically ill patients with VAP. METHODS VAP cases were identified from a cohort of COVID-19 patients (n=243) admitted to the Medical ICU (IRB #i22-00616) based on clinical and radiographic criteria. Lower airway samples (bronchoalveolar lavage [BAL] and tracheal aspirates) were collected for microbiome analysis. Clinical cultures were collected at the discretion of the treating clinician. Relative abundance (based on RNA metatranscriptomic sequencing of lower airway samples) was calculated from QIIME2 pipelines and compared to the clinical culture results. RESULTS There were 104 VAP events (92 participants had one VAP, 12 had >1 VAP events; 92 participants/243 total participants). The most common pathogens isolated in culture were Staphylococcus aureus (n=20), Klebsiella spp. (n=25 total, K. pneumoniae n=13, K. aerogenes n=9, and K. oxytoca n=6), Pseudomonas aeruginosa (n=15), Escherichia coli (n=15), and Stenotrophomonas maltophilia (n=6). Many samples had no growth (n=32), normal flora (n=73), or were polymicrobial (n=30). There was higher relative abundance of S. aureus, P. aeruginosa, Klebsiella spp., E. coli, and S. maltophilia in the microbiome for cultures positive for each respective pathogen (Figure 1A-E). S. aureus and P. aeruginosa were more often the dominant species (defined as >50% relative abundance) in positive cultures compared to other pathogens, particularly K. aerogenes and oxytoca (Figure 1C). Cultures that grew normal flora or were negative had many pathogens present, and some lower airway samples had pathogens present in high amounts (Figure 1F-G). CONCLUSIONS For VAP patients with an identified pathogen in culture, there was a higher relative abundance of that respective pathogen in the lower airway microbiome. However, the pathogen was often not the dominant organism. Respiratory cultures often did not identify a pathogen despite the high relative abundance of pathogens in the lower airway microbiome, suggesting a paradoxical relationship between presence of pathogen in the microbiome and detection in culture. Next steps include investigating the lower airway microbiome community composition other than the pathogen of interest to help elucidate VAP pathogenesis. Our current clinical methods of detecting VAP pathogens select for pathogen growth, and perhaps utilizing a multipronged approach combining culture and non-culture-based methods would improve diagnosis.

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