Snapshot A 28-year-old man presents to the emergency department with worsening shortness of breath and fever. His symptoms began approximately 1 week ago. He has a medical history of HIV infection and he is non-adherent with his antiretroviral therapy. Physical examination is notable for bilateral adventitial sounds. A chest radiograph demonstrates bilateral interstitial infiltrates. His CD4 count is 180/uL. He is started on trimethoprim-sulfamethoxazole. Introduction Mechanism of action dihydropteroate synthase inhibitor, impairing folate synthesis has bactericidal activity when combined with trimethoprim Mechanism of resistance altered bacterial dihydropteroate synthase Clinical use gram-positive organisms gram-negative organisms Nocardia Adverse reaction hypersensitivity reactions hemolysis in patients with G6PD deficiency tubulointerstitial nephritis Stevens-Johnson syndrome photosensitivity infantile kernicterus displaces drugs that bind to albumin e.g., raises warfarin levels