Randomised controlled trial of single-dose antibiotic prophylaxis in surgical treatment of closed fractures: the Dutch Trauma Trial

Abstract

Background: The efficacy of prophylactic antibiotics in fracture surgery remains controversial for lack of well-documented prospective studies. We report here the findings of the Dutch Trauma Trial, a prospective, randomised, double-blind, placebo-controlled study of antibiotic prophylaxis in the primary operative treatment of limb fractures. Ceftriaxone was chosen because of its pharmacokinetic profile, including high serum levels, high tissue penetration, and long elimination half-life, makes it suitable for single-dose prophylaxis.

Methods: Patients aged 18 years or more, attending one of fourteen Dutch centres for acute treatment of closed fractures, were randomly allocated to a single preoperative dose of ceftriaxone 2 g or placebo, and evaluated for development of wound infection and nosocomial infection at 10 days, 30 days, and 120 days. To assess the effects of drop-outs and withdrawals, best-case and worst-case analyses were performed.

Findings: A total of 2195 patients were included. The incidence of superficial and deep wound infections after placebo was 8.3%, compared with 3.6% in the ceftriaxone group (p < 0.001, Pearson chi 2-test). The rate of nosocomial infection in the first month was 10.2% with placebo and 2.3% with ceftriaxone (p < 0.001, Pearson chi 2-test). Gram-positive bacteria were found in 74.5% of wound infections and 13.4% of nosocomial infections.

Interpretation: Adequate single-dose prophylaxis with a long-acting broad-spectrum antibiotic substantially reduces the incidence of wound infection and early nosocomial infection after surgery for closed fractures.