To evaluate the role of nitrofurantoin (NFT) prophylaxis in a prospective randomized control study. Urosepsis is an important complication after percutaneous nephrolithotomy (PNL). Risk increases by around 4 times with larger stones and hydronephrosis (HDN).

Patients with stones ≥2.5 cm and/or HDN and sterile urine undergoing PNL were randomized into 2 groups. Standard perioperative antibiotic prophylaxis was the same in both groups. One group received sustained-released NFT 100 mg b.i.d. for 7 days preoperatively, and the other did not. Preoperative urine, intraoperative renal pelvic urine, and stone cultures were obtained. Postoperative occurrence of SIRS was considered urosepsis after excluding other causes. Serum samples were collected immediately after PNL and stored at −20°C. Serum endotoxin was estimated using Limulus Amoebocyte Lysate gelation technique (Sigma Aldrich, Saint Louis, Missouri). The operating surgeons and the microbiologist were blinded to the group distribution.

Of 101 patients, 48 received nitrofurantoin prophylaxis. Both groups were comparable for age, gender, stone burden, degree of HDN, duration of operation, and intraoperative blood loss. There was significantly low positive pelvic urine culture (0% vs 9.8%, RR 4.95, P = .001), positive stone culture (8.3% vs 30.2%, RR 3.64, P = .001), endotoxemia (17.5% vs 41.9%, OR 0.22, P = .016), and systemic inflammatory response system (19% vs 49%, OR 0.31, P = .01) in patients receiving NFT prophylaxis.

Prophylaxis with NFT for a week before PNL is beneficial in the prevention of urosepsis and endotoxemia in patients with larger stones and HDN. NFT covers most of the urinary isolates and is preferred in areas of fluoroquinolone resistance.