Ceftriaxone, a third-generation cephalosporin, is primarily eliminated by the kidneys. While ceftriaxone-induced gallstones and nephrolithiasis are well-documented in children, reports in adults are rare. We present a case of ceftriaxone-associated urolithiasis occurring within a month after appendicitis treatment.

Case presentation: A 21-year-old female with severe intellectual disabilities and bipolar disorder underwent laparoscopic appendectomy for appendicitis with abscess on 2025/01/17, followed by laparoscopic adhesiolysis for postoperative ileus 6 days later. During her first admission, she received ceftriaxone 2000 mg Q12H IVD for 7 days and was NPO for 6 days due to ileus. Discharged stable on 02/05, she returned to the ER the same day with recurrent vomiting. Abdominal CT showed a 1 cm right upper ureteral stone with hydronephrosis and residual retroperitoneal abscess. A prior CT ruled out pre-existing stones, leading to a diagnosis of ceftriaxone-associated urolithiasis. Due to persistent nausea, she underwent right ureteroscopy and spontaneous stone passage into the bladder was observed. A Double-J stent was placed. Her postoperative course was uneventful, and she was discharged on 02/12 with stable vital signs, no nausea or vomiting, and good oral intake.

Discussion: Ceftriaxone is primarily eliminated by the kidneys (45–60%) and bile. It binds with calcium, forming crystals and pseudolithiasis. Ceftriaxone-associated urolithiasis typically develops within 4–7 days of antibiotic initiation and resolves within 2–63 days after discontinuation. However, in some cases, resolution may take up to a year, and severe nephrolithiasis leading to post-renal acute kidney failure has been reported. Study has shown that ceftriaxone-induced crystallization in artificial urine is significantly reduced at pH 4.5–5.0 compared to pH 6.0. Additionally, alkaline urine and hypocitraturia are known to predispose patients to ceftriaxone-induced urolithiasis. Other risk factors include fasting, prolonged immobilization, female sex, renal impairment, hypercalcemia, high-dose ceftriaxone and extended treatment duration. In this patient, multiple risk factors were present. Prior appendicitis with a right retroperitoneal abscess may have impaired right ureteral peristalsis. Combined with prolonged NPO status, high-dose ceftriaxone, and bladder urinary retention during the previous hospitalization, these factors likely contributed to stone formation and deposition.

Recognizing this adverse effect is essential, especially in high-risk patients receiving ceftriaxone. For persistent symptoms or acute kidney injury, drainage may be needed. Otherwise, conservative management with or without urine acidification may help dissolve ceftriaxone-induced urolithiasis.