Antibiotics Pre-Appendectomy Don't Lower Perforation Risk

Medscape

2 days ago

Antibiotic treatment while awaiting appendectomy does not lower risk for appendiceal perforation in patients with uncomplicated acute appendicitis, according to a new study.
While the percentage of surgical site infections (SSIs) was small for both groups, patients who received antibiotics during the waiting period had lower rates of these infections.
The trial — titled PERFECT-Antibiotics — was a substudy embedded in a larger PERFECT clinical trial, which aimed to determine whether an in-hospital delay of appendectomy resulted in increased risk for appendiceal perforation when compared to emergent surgery.
The trial 'concluded that appendectomy does not need to be performed promptly in acute uncomplicated appendicitis and can be scheduled within 24 hours without increasing complications,' senior author Panu Mentula, MD, of the department of Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland, and colleagues wrote in the study. 'The next question is whether preoperatively started antibiotic treatment reduces the risk of appendiceal perforations.'
The findings were published online in JAMA Surgery on May 14, 2025.
Trial Design
PERFECT-Antibiotics was an open-label, randomized trial conducted at two hospitals in Finland and one hospital in Norway. Researchers enrolled 1774 individuals diagnosed with acute uncomplicated appendicitis, diagnosed clinically or via imaging. Patients were placed in one of two groups: The antibiotic group received intravenous (IV) cefuroxime (1500 mg) and metronidazole (500 mg) every 8 hours until surgery, while the nonantibiotic group waited for surgery without antibiotics.
All patients received one dose of IV cefuroxime (1500 mg) and metronidazole (500 mg) during anesthesia induction. The primary outcome was perforated appendicitis and secondary outcomes included complication rate and SSIs within 30 days of follow-up.
The median age of patients was 35 years (interquartile range [IQR], 28-46 years), and 55% of patients were men. Patients waited a median time of 9 hours (IQR, 4.3-15.5) from study randomization to undergoing surgery.
No Difference in Appendiceal Perforation
Of the 888 patients in the preoperative antibiotic group, 26.2% received one dose, 38.7% received two doses, 22.6% received three doses, and 11.8% received four or more doses of antibiotics, including the antibiotic dose given during anesthesia. A total of 74 patients (8.3%) in this group had a perforated appendix.
Of the 886 patients not given preoperative antibiotics, 79 (8.9%) had a perforated appendix, which met the predetermined noninferiority threshold.
The groups had similar complication rates over the 30-day follow-up, though SSIs were lower in the antibiotic group (1.6%) than the no antibiotic group (3.2%).
The researchers estimated that the number needed to treat for antibiotic therapy was 63 for SSIs, 83 for intra-abdominal SSI, and 125 for reintervention.
'Although longer preoperative antibiotic treatment resulted in slightly lower rate of postoperative infectious complications, the actual difference was very small and probably clinically not significant to justify longer preoperative antibiotic treatment,' Mentula and colleagues wrote.
Lower Infection Rates With Antibiotics
Commenting on the study for Medscape Medical News , Theodore Pappas, MD, professor of surgery at Duke University School of Medicine in Durham, North Carolina, placed greater importance on these secondary outcomes.
Intra-abdominal infections, a subset of SSIs, were more than twice as common in the no-antibiotic group (1.9%) than in the antibiotic group (0.7%; P = .02). Positive blood cultures were also more common in the no-antibiotic group than the antibiotic group ( P = .02).
While the authors qualified these results, 'the reality was it was better to use antibiotics,' he said.
There was also a 'big overlap between the two groups,' he said, which may have muted differences between the two groups. For example, one fourth of patients in the antibiotic group received only one dose of antibiotics, the same treatment regimen as the no-antibiotic group.
'Although protocol required prophylaxis in all patients in the induction of anesthesia, some clinicians thought that it was unnecessary, because antibiotics had already been given only a couple of hours ago' in patients in the antibiotic group, Mentula told Medscape Medical News . She did not think that would affect the study's results.
The PERFECT trial and the antibiotics subtrial answer two important questions that have been asked for years, Pappas continued: Whether appendectomy for uncomplicated acute appendicitis needs to be performed emergently and if antibiotics administered while waiting for surgery improve outcomes.
'Basically, the study shows that you probably should keep them on antibiotics while you're waiting,' he said.