N4-Acetyl-Sulfamethoxazole Bladder Stones Caused by Trimethoprim-Sulfamethoxazole Prophylaxis: A Report of Two Cases.

The combination antimicrobial trimethoprim-sulfamethoxazole (TMP-SMX) has a broad spectrum of activity and is used as a prophylactic for various infections. Drug-induced urolithiasis is a rare side effect of TMP-SMX that results from the precipitation of its metabolite N4-acetyl-sulfamethoxazole. There are only two reports of bladder stones associated with TMP-SMX, both of which occurred in patients with a history of recurrent urinary tract infections (UTIs). At our institution, an 80-year-old male with a complex medical history including benign prostatic hyperplasia (BPH) and a chronic prosthetic joint infection on long-term amoxicillin and TMP-SMX presented for evaluation of an incidental 2.4 cm bladder stone. Surgical intervention was initially deferred due to patient preference, but he later developed gross hematuria and decided to undergo cystoscopy with cystolitholapaxy and bilateral retrograde pyelogram. The procedure was completed without complications. Analysis of stone fragments revealed that they were 100% N4-acetyl-sulfamethoxazole. Months later, a 70-year-old male with multiple sclerosis and neurogenic bladder complicated by recurrent UTIs managed with a suprapubic catheter and TMP-SMX prophylaxis was found to have multiple bladder stones causing obstructive symptoms. These stones were similarly treated with cystolitholapaxy and identified as 100% N4-acetyl-sulfamethoxazole. Bladder stones caused by TMP-SMX have been rarely reported in people like our 70-year-old patient with an abnormal urinary metabolic profile, indicated by a history of urolithiasis or UTIs. Our other patient did not have either of these risk factors, but he did have lower urinary tract symptoms due to BPH. His case may serve as a caution to the use of TMP-SMX in the setting of chronic urinary stasis due to bladder outlet obstruction.