BACKGROUND Chryseobacterium gleum (C. gleum) is a rare but concerning device-associated infection that can cause urinary tract infections and pneumonia. It produces a biofilm and has intrinsic resistance to a wide array of broad-spectrum agents. Risk factors include neonate or immunocompromised states, intensive care unit admission for more than 21 days, broad-spectrum antibiotic exposure, indwelling devices, and mechanical ventilation. CASE REPORT A 61-year-old cachectic man presented in the United States with community-acquired pneumonia and immediately decompensated, requiring ventilator support. Despite starting broad-spectrum antibiotics, the patient developed fever, leukocytosis, and additional desaturation episodes. The patient's respiratory culture grew numerous C. gleum and few Stenotrophomonas (Xanthomonas) maltophilia. He also had a positive urine streptococcal pneumonia antigen. Broad-spectrum agents were discontinued after prolonged treatment due to a continued worsening clinical picture, and the patient was started on trimethoprim-sulfamethoxazole to cover C. gleum. The patient showed rapid clinical improvement on trimethoprim-sulfamethoxazole, with resolution of symptoms on post-discharge follow-up. CONCLUSIONS To the best of our knowledge, this is the first case report of a documented case of a patient with C. gleum respiratory infection successfully treated solely with trimethoprim-sulfamethoxazole. The expedient identification of C. gleum is essential for proper treatment. The literature has consistently shown isolated respiratory C. gleum strains to be largely susceptible to fluoroquinolones, piperacillin-tazobactam, or trimethoprim-sulfamethoxazole.