Abstract Background Pseudomonas aeruginosa (PA) poses a significant clinical challenge due to its high antibiotic resistance. While microbial communities aid in spreading antibiotic resistance genes (ARGs), their role in the emergence of multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is unclear. This study examines the impact of bacterial interactions on MDR-PA prevalence and underlying mechanisms. Methods This retrospective cohort study analysed 2965 PA-positive culture patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV version 3.1) database, stratified by bacterial co-detection with PA. Propensity score matching (PSM) and logistic regression were used. Metagenomic sequencing was performed on deep endotracheal secretions from 19 PA ventilator-associated pneumonia (VAP) patients, constructing an ARGs dissemination network within the lower respiratory tract (LRT) microbiota. Comparative analysis of LRT microbiota and ARGs profiles was conducted between PA-VAP survivors and non-survivors. Results Patients with bacterial co-detection with PA had a significantly higher MDR-PA prevalence and mortality than those with PA-only detection. Logistic regression identified bacterial co-detection as an independent risk factor for MDR-PA (adjusted OR 2.14; 95% CI 1.64–2.83, P 0.001) and subsequent mortality (adjusted OR 1.67; 95% CI 1.30–2.14, P 0.001). Metagenomic analysis of 19 PA-VAP cases suggested that horizontal gene transfer (HGT) may facilitate inter-species dissemination of ARGs (e.g. eptB, smeE, ANT(4’)-Ia) between PA and other co-colonizing LRT microbiota. Distinct ARG profiles were observed between PA-VAP survivors and non-survivors. Conclusion Our findings indicate that bacterial co-detection with PA elevates the risk of MDR-PA and worsens clinical outcomes, potentially driven by HGT-mediated ARG exchange within the host microbiota.
Zhang et al. (Wed,) studied this question.