Original Investigation 

May 14, 2025

Role of Preoperative Antibiotic Treatment While Awaiting Appendectomy: The PERFECT-Antibiotics Randomized Clinical Trial

Karoliina Jalava, Ville Sallinen, Hanna Lampela, et al

JAMA Surg. Published online May 14, 2025. doi:10.1001/jamasurg.2025.1212

Key Points

Question  Is waiting for surgery without antibiotic treatment noninferior to waiting with antibiotic treatment in acute uncomplicated appendicitis?

Findings  This randomized clinical trial included 1774 randomized patients with presumed uncomplicated acute appendicitis diagnosed clinically or by imaging. Waiting for surgery without antibiotic treatment was noninferior to antibiotic treatment in the risk of appendiceal perforation.

Meaning  Findings suggest that preoperative antibiotic treatment does not affect the severity of appendicitis, and waiting for surgery without antibiotics does not significantly affect the outcome.

Abstract

Importance  Antibiotics are thought to decelerate inflammation progression and reduce complications in acute uncomplicated appendicitis. The evidence of their effectiveness is insufficient, and treatment practices vary widely.

Objective  To investigate the effect of preoperatively started antibiotic treatment on the rate of appendiceal perforation.

Design, Setting, and Participants  This multicenter, noninferiority, open-label randomized clinical trial was conducted in 2 hospitals in Finland and 1 hospital in Norway between May 18, 2020, and January 22, 2023. Data analysis was performed from March 2023 to March 2024. Eligible patients were adults (aged >18 years) diagnosed with presumed uncomplicated acute appendicitis. Patients with allergies or other contraindications to study antibiotics, previously started antibiotic treatment, pregnancy, a suspicion of perforated appendicitis, or other reasons to perform prompt surgery were excluded. Patients were randomized 1:1 with a web-based service simultaneously as the laparoscopic appendectomy was scheduled.

Interventions  Antibiotic treatment started while waiting for surgery (cefuroxime, 1500 mg, and metronidazole, 500 mg, every 8 hours until the surgery) or waiting without antibiotic treatment. Patients in both groups received a single prophylactic dose of antibiotics in the induction of anesthesia.

Main Outcomes and Measures  The primary outcome was perforated appendicitis diagnosed during surgery. The absolute difference in perforation rates was compared between the groups by an intention-to-treat analysis, and the predefined noninferiority margin was 5 percentage points. Secondary outcomes included surgical site infections within 30 days.

Results  A total of 1797 patients were randomly assigned to either the antibiotic group (n = 901) or no-antibiotic group (n = 896). Median (IQR) patient age was 35 (28-46) years, and 793 patients (45%) were female. After randomization, 23 patients (1.3%) were excluded, leaving 1774 patients for the intention-to-treat analyses. The difference between the appendiceal perforation rates met the noninferiority threshold: 74 of 888 patients in the antibiotic group (8.3%) vs 79 of 886 patients in the no-antibiotic group (8.9%; absolute difference, 0.6 percentage points; 95% CI, −2.0 to 3.2 percentage points; P = .66; risk ratio, 1.07; 95% CI, 0.79 to 1.45). For secondary outcome, the surgical site infection rate was slightly lower in the antibiotic group (14 of 887 [1.6%]) vs the no-antibiotic group (28 of 886 [3.2%]; absolute difference, 1.6 percentage points; 95% CI, 0.2 to 3.0 percentage points; P = .03).

Conclusions and Relevance  In this multicenter noninferiority randomized clinical trial, preoperatively started antibiotic treatment did not decrease the risk of appendiceal perforation when appendectomy was performed within 24 hours in adult patients with presumed uncomplicated acute appendicitis.

Trial Registration  EudraCT Identifier: 2019-002348-26