Early Preoperative Antibiotics Before Appendectomy
July 1, 2025
By Jake Scott, MD
Synopsis: Pre-incision treatment did not reduce intra-operative perforation, and likewise did not change purulent contamination, peri-appendicular abscess, or histologic gangrene. It did lower 30-day surgical-site infection (SSI) (1.6% vs. 3.2%; P = 0.03) and re-intervention for SSI (0.3% vs. 1.1%), but the effect was marginally significant, giving a number-needed-to-treat of 63 for any SSI and 125 for a re-intervention.
Source: Jalava K, Sallinen V, Lampela H, et al. Role of preoperative antibiotic treatment while awaiting appendectomy: The PERFECT-Antibiotics randomized clinical trial. JAMA Surg. 2025;May 14:e251212. doi:10.1001/jamasurg.2025.1212. [Online ahead of print].
The trial, conducted at two Finnish teaching hospitals and one Norwegian teaching hospital between May 2020 and January 2023, enrolled adults ≥ 18 years of age with an Adult Appendicitis Score ≥ 16 or imaging-confirmed uncomplicated disease.1 Exclusions included prior antibiotics, pregnancy, fever > 38.5 °C or C-reactive protein (CRP) ≥ 100 mg/L, imaging evidence of perforation, antibiotic allergy, or need for urgent surgery. All patients received a single prophylactic dose at induction of anesthesia. Pathologists were masked to allocation. Baseline characteristics were balanced (median age 35 years; 45% female; > 80% imaging-confirmed appendicitis; appendicolith on one-third of computed-tomography [CT] scans). Median in-hospital delay to incision was nine hours (interquartile range, 4-16).
The primary outcome was American Association for the Surgery of Trauma grade 3-5 perforation, which occurred in 74 of 888 patients (8.3%) given antibiotics and 79 of 886 patients (8.9%) without antibiotics (absolute difference, 0.6 percentage points; 95% confidence interval [CI], –2.0 to 3.2; P = 0.66), satisfying the five-percentage-point non-inferiority margin. Secondary endpoints favored the antibiotic arm only modestly: any SSI 1.6% vs. 3.2% (absolute difference, 1.6 percentage points; 95% CI, 0.2-3.0; P = 0.03) and intra-abdominal infection 0.7% vs. 1.9% (P = 0.02). There were no differences in purulent peritoneal contamination, peri-appendicular abscess, histologic gangrene, overall postoperative-complication rate, or hospital stay. Positive blood cultures were more frequent without antibiotics (0.9% vs. 0.1%).
Commentary
Observational data from a large Washington-state registry (9,048 adults) showed no association between in-hospital delay and perforation risk, a finding echoed by PERFECT-Antibiotics, which likewise found no perforation benefit from early broad-spectrum coverage.2 The World Society of Emergency Surgery 2020 guideline recommends a single pre-incision dose for uncomplicated appendicitis and discourages postoperative antibiotics.3 A Cochrane systematic review limited to appendectomy concluded that one preoperative dose is as effective as extended regimens for preventing postoperative infection.4 These sources align with the PERFECT-Antibiotics finding that additional hours of broad-spectrum coverage confer little clinical value.
Luminal obstruction by a fecalith is seen in less than half of modern CT series, and inflammation often precedes obstruction, suggesting that short antibiotic courses during brief in-hospital waits are unlikely to halt disease progression.5 The investigators calculated a number-needed-to-treat of 63 to prevent any surgical-site infection (SSI), 83 to prevent an intra-abdominal infection, and 125 to prevent an infection-related re-intervention — figures that underscore how little clinical gain is achieved at the cost of added antimicrobial exposure and resistance risk. Limitations of the PERFECT-Antibiotics trial include the open-label design and exclusion of complicated appendicitis, pediatric patients, and pregnancy. Centers with very high baseline SSI rates may judge a 1.6-percentage-point reduction worthwhile, but for most institutions a single-dose strategy appears sufficient.
Jake Scott, MD, is Clinical Associate Professor, Infectious Diseases and Geographic Medicine, Stanford University School of Medicine; Antimicrobial Stewardship Program Medical Director, Stanford Health Care Tri-Valley.
References
1. Jalava K, Sallinen V, Lampela H, et al. Role of preoperative antibiotic treatment while awaiting appendectomy: The PERFECT-Antibiotics randomized clinical trial. JAMA Surg. 2025;May 14:e251212. doi:10.1001/jamasurg.2025.1212. [Online ahead of print].
2. Drake FT, Mottey NE, Farrokhi ET, et al. Time to appendectomy and risk of perforation in acute appendicitis. JAMA Surg. 2014;149(8):837-844.
3. Di Saverio S, Podda M, De Simone B, et al. Diagnosis and treatment of acute appendicitis: 2020 update of the WSES Jerusalem guidelines. World J Emerg Surg. 2020;15(1):27.
4. Andersen BR, Kallehave FL, Andersen HK. Antibiotics versus placebo for prevention of postoperative infection after appendicectomy. Cochrane Database Syst Rev. 2003;(2):CD001439.
5. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-810.
Pre-incision treatment did not reduce intra-operative perforation, and likewise did not change purulent contamination, peri-appendicular abscess, or histologic gangrene. It did lower 30-day surgical-site infection (SSI) (1.6% vs. 3.2%; P = 0.03) and re-intervention for SSI (0.3% vs. 1.1%), but the effect was marginally significant, giving a number-needed-to-treat of 63 for any SSI and 125 for a re-intervention.
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