Four-year surveillance of major Gram-negative pathogens in a Saudi tertiary hospital: clinical distribution, comorbidity profiles, and antimicrobial resistance.

PURPOSE: To describe four-year diagnostic-distribution, burden, and antimicrobial-resistances of major Enterobacterales and Pseudomonas aeruginosa in a tertiary-care surveillance framework. PATIENTS AND METHODS: We retrospectively studied first non-duplicate-isolate per/patient/organism between 2022-2025 at a Saudi tertiary-care. Diagnostics used automated-platforms with GeneXpert-Carba-R employed parallel to cultures. Susceptibility interpretations used CLSI-breakpoints relevant to test-year. Annual-trends were assessed with grouped-binomial logistic-regression, and Benjamini-Hochberg false-discovery-rate correction was applied within prespecified analysis. RESULTS: Among 1,857 isolates, Klebsiella pneumoniae was most frequent (36.2%), followed by P. aeruginosa (33.4%), Escherichia coli (17.9%), and Enterobacter cloacae (12.3%). Mean patient age was 64.8 years, 51.3% isolates were from intensive-care, 37.4% from urine, and 80.8% records had comorbidity. K. pneumoniae showed overall ESBL (76.6%), CRE (59.9%), MDR (69.3%), panel-defined XDR (64.7%), and panel-defined PDR (15.2%) frequencies. Enterobacterales ESBL-positivity increased (58.1% to 76.8%;q <0.001), whereas meropenem non-susceptibility decreased (52.6% to 33.2%;q <0.001). In P. aeruginosa, ceftazidime non-susceptibility increased (55.2% to 78.6%;q <0.001), meropenem decreased (46.8% to 32.9%;q = 0.031), and tobramycin increased (22.2% to 45.7%;q = 0.030). Crude-comorbidity differences remained insignificant after false-discovery-rate correction. CONCLUSION: We show a persistent species-specific Gram-negative resistance burden, led by K. pneumoniae and accompanied by substantial P. aeruginosa non-susceptibility. This supports organism-specific detections, antibiograms and continued multicenter-surveillance linked to antimicrobial exposure, genomic-data, and patient outcomes.