Snapshot A 23-year-old woman presents to her primary care doctor for dysuria. Her symptoms began 2-3 days ago and are associated with urinary frequency and urgency. Physical examination is notable for suprapubic tenderness but there is no costovertebral angle tenderness. Urinalysis is remarkable for being leukocyte esterase positive with elevated white blood cells. Urine culture demonstrates > 100,000 CFU/mL E. coli. She is treated with trimethoprim-sulfamethoxazole. (Acute cystitis) Introduction Mechanism of action a reversible dihydrofolate reductase inhibitor, which impairs folate synthesis Clinical use used in combination with sulfonamides to treat urinary tract infections Shigella Salmonella Pneumocystis jirovecii pneumonia both treatment and prophylaxis Toxoplasmosis prophylaxis Adverse effects note that sequela of trimethoprim can be avoided with folinic acid supplementation megaloblastic anemia leukopenia granulocytopenia hyperkalemia via inhibition of amiloride-sensitive epithelial Na channels in the renal collecting duct