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We identified 91 cases of bacteremia due to Stenotrophomonas (Xanthomonas) maltophilia in a prospective, multicenter observational study. The patients were highly compromised; the majority had an underlying malignancy, had received immunosuppressive therapy, and had indwelling venous catheters. Although 94% of patients received an antimicrobial agent to which the blood isolate was susceptible, the mortality among these patients 14 days after the onset of bacteremia was 21%. Mortality was significantly correlated with the presence of a hematologic malignancy or neutropenia or transplantation, immunosuppressive therapy, and a severity-of-illness score of >4. S. maltophilia infection is associated with substantial morbidity and mortality among highly compromised patients. The organism is typically resistant to expanded spectrum β-lactam agents and aminoglycoside antibiotics. Trimethoprim …