Randomized trial of prophylactic antibiotics vs. placebo after midshaft-to-distal hypospadias repair: the PROPHY Study

• Published in: Journal of pediatric urology Vol. 18; no. 2; pp. 171 - 177
• Main Authors: Faasse, Mark A., Farhat, Walid A., Rosoklija, Ilina, Shannon, Rachel, Odeh, Rakan I., Yoshiba, Grace M., Zu'bi, Fadi, Balmert, Lauren C., Liu, Dennis B., Alyami, Fahad A., Beaumont, Jennifer L., Erickson, Daniel L., Gong, Edward M., Johnson, Emilie K., Judd, Sandra, Kaplan, William E., Kaushal, Gagan, Koyle, Martin A., Lindgren, Bruce W., Maizels, Max, Marcus, Charles R., McCarter, Kimberly L., Meyer, Theresa, Qureshi, Tarannum, Saunders, Megan, Thompson, Theresa, Yerkes, Elizabeth B., Cheng, Earl Y.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2022
• Subjects: Anti-bacterial agents; Antibiotic prophylaxis; Complications; Hypospadias; Surgical wound infection; Urinary tract infection; Antibiotic prophylaxis; Urinary tract infection; Anti-bacterial agents; Complications; DSMC; TMP-SMX; Hypospadias; Surgical wound infection; SSI; UTI; IV; ADR
• ISSN: 1477-5131; 1873-4898
• DOI: 10.1016/j.jpurol.2022.01.008

Use of prophylactic antibiotics after stented hypospadias repair is very common, but most research has not identified any clinical benefits of this practice. Only one study has found that postoperative prophylaxis reduces symptomatic urinary tract infections (UTIs). Data from the same trial suggested that prophylaxis may also reduce urethroplasty complications. No studies on this subject have been placebo-controlled. We performed a randomized, double-blind, placebo-controlled study to evaluate the effect of postoperative prophylactic antibiotics on the incidence of infection or urethroplasty complications after stented repair of midshaft-to-distal hypospadias. Boys were eligible for this multicenter trial if they had a primary, single-stage repair of mid-to-distal hypospadias with placement of an open-drainage urethral stent for an intended duration of 5–10 days. Participants were randomized in a double-blind fashion to receive oral trimethoprim-sulfamethoxazole or placebo twice daily for 10 days postoperatively. The primary outcome was a composite of symptomatic UTI, surgical site infection (SSI), and urethroplasty complications, including urethrocutaneous fistula, meatal stenosis, and dehiscence. Secondary outcomes included each component of the primary outcome as well as acute adverse drug reactions (ADRs) and C. difficile colitis. Infection or urethroplasty complications occurred in 10 of 45 boys (22%) assigned to receive antibiotic prophylaxis as compared with 5 of 48 (10%) who received placebo (relative risk [RR], 2.1; 95% confidence interval [CI], 0.8 to 5.8; p = 0.16). There were no significant differences between groups in symptomatic UTIs, SSIs, or any urethroplasty complications. Mild ADRs occurred in 3 of 45 boys (7%) assigned to antibiotics as compared with 5 of 48 (10%) given placebo (RR, 0.6; 95% CI, 0.2 to 2.5; p = 0.72). There were no moderate-to-severe ADRs, and no patients developed C. difficile colitis. In this placebo-controlled trial of 93 patients, prophylactic antibiotics were not found to reduce infection or urethroplasty complications after stented mid-to-distal hypospadias repair. The study did not reach its desired sample size and was therefore underpowered to independently support a conclusion that prophylaxis is not beneficial. However, the result is consistent with most prior research on this subject. NCT02096159Summary TableClinical outcomes of patients assigned to receive prophylactic trimethoprim-sulfamethoxazole (TMP-SMX) vs. placebo for 10 days after hypospadias repair.Summary TableTMP-SMX (n = 45)Placebo (n = 48)Relative risk (95% CI)p valueInfection or urethroplasty complications10 (22%)5 (10%)2.1 (0.8–5.8)0.16Symptomatic urinary tract infection2 (4%)3 (6%)0.7 (0.1–4.1)0.99Surgical site infection1 (2%)1 (2%)1.1 (0.1–16.6)0.99Urethrocutaneous fistula5 (11%)1 (2%)5.3 (0.7–43.9)0.10Meatal stenosis1 (2%)0–0.48Urethral stricture00––Dehiscence1 (2%)0–0.48Urethral diverticulum00––Mild adverse drug reaction3 (7%)5 (10%)0.6 (0.2–2.5)0.72Moderate-to-severe adverse drug reaction00––C. difficile colitis00––