medwireNews: Routine use of preoperative antibiotics does not decrease the risk for appendiceal perforation in adults undergoing appendectomy for presumed uncomplicated acute appendicitis, according to the PERFECT-Antibiotics trial.
While there has been strong evidence that preoperative antibiotic prophylaxis effectively reduces postoperative infectious complications from appendectomy, its impact on the risk of appendiceal perforation “has remained unclear” until now, write Panu Mentula (Helsinki University Hospital, Finland) and colleagues in JAMA Surgery.
The open-label trial randomly assigned 1797 patients to receive preoperative antibiotics (n=901) or no antibiotics (n=896) when admitted to the inpatient ward to wait for surgery. Those in the antibiotic group received intravenous cefuroxime 1500 mg and metronidazole 500 mg every 8 hours until surgery; both groups received pain medication and a single prophylactic intravenous dose of antibiotics during the induction of anesthesia.
Eligible patients had a score of 16 points or higher on the Adult Appendicitis Score or a diagnosis via ultrasonography, computed tomography (CT), or magnetic resonance imaging.
The baseline demographics of the patients were similar across the groups, with a median age of 35 years and 55.3% of participants being men. Patients waited in hospital for a median of 9 hours, and the antibiotic group received the treatment for a median of 8 hours.
The participants had a median score of 15 points on the Adult Appendicitis Score, 84.2% of appendicitis diagnoses were confirmed by imaging, and appendicolith was detected in 33.3% of 1199 patients scanned by CT.
Mentula et al report that perforated appendicitis, the primary outcome of the study, occurred in 8.3% and 8.9% of patients in the antibiotic and nonantibiotic groups, respectively. The absolute difference of 0.6 percentage points was within the noninferiority margin of 5.0 percentage points.
The two groups also had similar rates of clinically undetectable perforations found by pathologic examination (0.2 vs 0.1%, respectively) and complications (6.0 vs 7.1%), and similar lengths of hospital stay (geometric mean=35 hours in both groups).
The investigators also found no significant differences between the groups in terms of secondary outcomes, including the Sunshine Appendicitis Grading Scale classification; rates of conversion to open surgery; patient-reported pain; pathologic verification of macroscopic and microscopic perforations; and histopathologic diagnosis of gangrene or perforation.
While 11.7% of the antibiotic group and 2.4% of the nonantibiotic group did not receive the planned treatments, similar results also applied when only considering those patients who did.
However, the researchers note that preoperative antibiotic treatment slightly decreased the rate of postoperative surgical site infections (SSIs) compared with no antibiotics, with corresponding rates of 1.6% and 3.2%. This was driven mainly by intra-abdominal infections, which occurred in 0.7% versus 1.9% of the antibiotic and nonantibiotic groups, respectively. SSIs also led to reintervention in a corresponding 0.3% versus 1.0% of patients.
The antibiotic group had fewer positive blood cultures than the nonantibiotic group, with corresponding rates of 0.1% and 0.9%. They also typically received more than one dose of intravenous antibiotics, with just 26.2% of patients receiving one dose versus 97.3% of those in the nonantibiotic group.
Since other randomized trials have also found no benefit of nonoperative antibiotic treatment over placebo in patients without appendicolith or severe systemic illness, “one could speculate that antibiotics usage in nonoperative treatment of uncomplicated appendicitis may be futile,” the authors write.
Mentula and colleagues acknowledge the unblinded protocol as a study limitation, although they estimated that it would not affect the main results, and pathologists were blinded to group assignment.
Additionally, there was a lower rate of perforated appendix than expected, making the absolute noninferiority margin too high, although they say that the margin is still clinically valid.
“Although longer preoperative antibiotic treatment resulted in [a] slightly lower rate of postoperative infectious complications, the actual difference was very small and probably clinically not significant to justify longer preoperative antibiotic treatment,” they conclude.
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