Gastrointestinal Microbiota Disruption and Risk of Colonization With Carbapenem-resistant Pseudomonas aeruginosa in Intensive Care Unit Patients

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) can colonize the gastrointestinal (GI) tract of intensive care unit (ICU) patients and CRPA colonization puts patients at increased risk of CRPA infection. Prior studies have not examined relationships between the microbiota, medications, and CRPA colonization-acquisition. Methods: Data and peri-rectal swabs were obtained from a cohort of ICU patients at the University of Maryland Medical Center. Patients (N=109) were classified into three groups by CRPA colonization-acquisition status and antimicrobial exposure. We conducted 16S rRNA gene sequencing of an ICU admission swab and ≥ one additional swab and evaluated associations between patient characteristics, medications, the GI microbiota, and CRPA colonization-acquisition. Results: ICU patients had low levels of diversity and high relative abundance of pathobionts. Piperacillin-tazobactam was prescribed more frequently to patients with CRPA colonization-acquisition than those without. Piperacillin-tazobactam was associated with low abundance of potentially protective taxa (e.g., Lactobacillus and Clostridiales) and increased risk of Enterococcus domination [odds ratio (OR) 5.50; 95% confidence interval (CI) (2.03-14.92)]. Opioids were associated with dysbiosis in patients who did not receive antibiotics; potentially protective Blautia and Lactobacillus were higher in patients who did not receive opioids. A group of correlated taxa, identified at ICU admission, were associated with lower risk of CRPA colonization-acquisition [OR 0.58; 95% CI (0.38-0.87)]. Conclusions: Antibiotics differed in their impact on the microbiota with piperacillin-tazobactam being particularly damaging. Certain bacterial taxa (e.g., Clostridiales) were negatively associated with CRPA colonization-acquisition. These taxa may be markers of risk for CRPA colonization-acquisition and/or serve a protective role.