Multidrug-Resistant Stenotrophomonas maltophilia Infections in Critically Ill and Immunocompromised Patients: Clinical Characteristics and Therapeutic Outcomes

Objectives Stenotrophomonas maltophilia is an emerging multidrug-resistant opportunistic pathogen associated with high morbidity and mortality, particularly among critically ill and immunocompromised patients. Data on trimethoprim-sulfamethoxazole (TMP-SMX)-resistant isolates remain limited globally and in Saudi Arabia. Methods We conducted a retrospective cohort study at a tertiary care center including adult patients with TMP-SMX-resistant S. maltophilia isolated from blood or respiratory specimens between May 2016 and April 2025. Demographic, microbiological, treatment, and outcome data were analyzed. Results Among 949 blood or respiratory S. maltophilia isolates screened, 79 TMP-SMX-resistant cases were identified (8.3%). Respiratory specimens accounted for 89.9% of resistant isolates, while blood culture isolates represented 10.1%. True infections accounted for 36 cases (45.6%), while the remaining 43 cases (54.4%) were classified as colonization. TMP-SMX resistance increased from 3.4% of isolates in 2017 to approximately 10% in 2024, with a marked rise after 2020. Patients were predominantly older adults (median age 66 years), with frequent ICU exposure (84.8%) and significant comorbidities. Overall 30-day and 180-day mortality rates were 34.2% and 49.4%, respectively. Minocycline demonstrated the highest susceptibility (75%), whereas levofloxacin susceptibility was limited (33.3%). Combination therapy was associated with numerically higher survival compared with monotherapy at both 30 and 180 days, although these differences were not statistically significant. Conclusions TMP-SMX-resistant S. maltophilia isolates are increasingly identified during the study periord, particularly among critically ill patients, and are associated with substantial mortality. Combination therapy was associated with numerically higher survival, but differences were not statistically significant. Larger comparative studies are needed to determine whether combination therapy improves clinical outcomes.