A retrospective study evaluated factors influencing pneumonia severity index (PSI) in patients with culture-proven bacterial pneumonia at a tertiary care center from January 2019 to April 2023. Most patients were at least 65 years of age and had at least one comorbidity. Gram-negative bacteria predominated, while Pseudomonas aeruginosa was most often isolated. Multidrug resistance (MDR) most often occurred in Acinetobacter baumannii, Klebsiella spp. and Escherichia coli. Higher PSI scores were significantly associated with greater comorbidity, the presence of MDR pathogens, increased values of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune inflammation index (SII), and lower albumin levels (p < 0.05). Patients with MDR pathogens had a significantly higher mean PSI score than patients without MDR. The study highlights the importance of considering comorbidity, antimicrobial resistance, and immuno-inflammatory biomarkers in risk stratification.