The nonoperative management of acute uncomplicated appendicitis using amoxicillin plus clavulanic acid did not prove to be as effective as appendectomy in an open-label, randomized, noninferiority trial.
The rates of postintervention peritonitis in 243 patients randomized to receive either amoxicillin plus clavulanic acid (3 g) daily for 8-15 days or emergency appendectomy were 8% and 2% in the groups, respectively. The difference was statistically significant, Dr. Corrine Vons of the Hopital Jean Verdier, Bondy, France and her colleagues reported in the May 7 issue of The Lancet.
Photo credit: Flickr user Ed Uthman (Creative Commons)
Longitudinal section of an inflamed appendix removed from a 10-year-old boy.
Furthermore, 14 (12%) of the 120 patients in the antibiotic group underwent an appendectomy in the first 30 days following intervention, and 30 (29%) of 102 patients followed beyond 30 days underwent appendectomy between 30 days and 12 months following intervention (at a median of 4.2 months); 26 of those patients had acute appendicitis, the investigators said (Lancet 2011;377:1573-9).
Patients in the multicenter study were adults aged 18-68 years with uncomplicated acute appendicitis on computed tomography who were enrolled between mid March 2004, and mid-January 2007. No differences were seen between the groups on secondary end points, including the median duration of severe pain, days in the hospital, or absence from work, nor were differences seen in the rate of postintervention complications in the groups.
"Overall, 81 (68%) of 120 patients did not need an [appendectomy] for acute appendicitis in the antibiotic group during the 1-year follow-up," the investigators noted.
However, antibiotic treatment was not shown to be noninferior, because the upper limit of the two-sided 95% confidence interval of 0.3-12.1 for the difference in rates was not lower than the prespecified limit of 10 percentage points, and the investigators thus concluded that emergency appendectomy remains the gold standard for acute uncomplicated appendicitis.
Acute appendicitis is the most common indication for surgical intervention among patients admitted to the hospital with acute abdominal pain, and 80% of cases are uncomplicated. Despite findings from several studies – including four randomized trials – indicating that nonoperative intervention with antibiotics might be acceptable, the approach to patients with acute appendicitis has not changed.
"Trials that show that acute appendicitis can be treated successfully with antibiotics were weakened by several design limitations," the investigators explained, noting that they attempted in the current study to avoid such design flaws.
For example, in the prior studies, diagnosis of uncomplicated appendicitis was not supported by systematic CT-scan assessment, but in the current study, CT scans were used to select patients with uncomplicated appendicitis before randomization. Despite the CT findings, however, 18% of 119 patients in the surgery group were found at the time of surgery to have complicated appendicitis.
The authors conceded that the finding that antibiotic treatment was inferior relative to appendectomy in patients with uncomplicated acute appendicitis in this study might be related to the proportion of patients with complicated disease who were erroneously included and randomized. They noted that it remains difficult to distinguish between uncomplicated and complicated appendicitis even with multiple-detector CT scans.
The findings could also be related to the increasingly common resistance of appendicitis, and in particular Escherichia coli, to amoxicillin plus clavulanic acid, they wrote.
Future studies should focus on the use of new diagnostic techniques for improved patient selection, and third-generation cephalosporins could be used, although they are not yet recommended, they wrote.
The study was funded by the French Ministry of Health, Programme Hospitalier de Recherche Clinique 2002. Dr. Vons and her colleagues declared having no relevant financial disclosures.