Antibiotics show promise as primary treatment in patients with acute uncomplicated appendicitis

Appendicitis image

The appendix is a blind-ended tube connected to the cecum in the colon. It may be vestigial, but it also seems to act as a repository of useful bacteria that can replenish the gut microbiome after disease has depleted it. Acute appendicitis can result from viral, bacterial, or fungal infection and obstruction of the appendix lumen. Bacteria in the appendix multiply rapidly, causing swelling, and the walls of the appendix gradually break down. Appendix rupture can occur, which can result in peritonitis and eventually sepsis.

Since the late 1800s, physicians have assumed that without surgery, uncomplicated appendicitis cases would progress to perforated appendicitis. Thus, appendectomy has been the standard of care for treatment of acute appendicitis ever since. Starting in the early 1980s, appendectomy has been performed laparascopically.

As Dr. Edward H. Livingston points out in a recent JAMA editorial, while the standard of care for appendicitis treatment has not changed in over 100 years, advances in computed tomography (CT) imaging have nearly perfected diagnostic accuracy. In addition, new broad-spectrum antibiotics show promise in effectively wiping out the organisms that cause serious complications in appendicitis. Two recent studies that compared appendectomy vs. antibiotics as primary treatment for acute appendicitis are summarized here:

The Appendicitis Acuta (APPAC) study, conducted by Finnish researchers and reported in JAMA June 16, 2015, compared antibiotic therapy with appendectomy in the treatment of acute appendicitis. In this multicenter, randomized, open-label noninferiority study, 530 patients ages 18 to 60 years with acute uncomplicated appendicitis confirmed by CT scan were enrolled. Patients were randomly assigned 1:1 to either standard open appendectomy or antibiotic therapy (IV ertapenem 1 g/d for 3 days, followed by oral levofloxacin 500 mg/d and metronidazole 500 mg tid for 7 days). Treatment success was defined in the surgery group as successful completion of the appendectomy and in the antibiotic group as discharge from the hospital without the need for surgery and no recurrent appendicitis during a 1-year follow-up period. A noninferiority margin of 24% was predefined.

All but 1 patient in the surgery group (272/273; 99.6% success rate) had a successful appendectomy. In the antibiotic group, of the 256 patients still enrolled at 1 year, 70 (27.3%) had undergone appendectomy and 186 (72.7% success rate) had not required appendectomy. This reflects a 27% difference in treatment efficacy between groups (intent-to-treat analysis); thus the noninferiority margin was not met. Of the 70 patients in the antibiotic group who later required appendectomy, 58 (82.9%) had uncomplicated appendicitis, 7 (10.0%) had complicated acute appendicitis, and 5 (7.1%) did not have appendicitis but received appendectomy for suspected recurrence. No intra-abdominal abscesses or other major complications were reported in this group.

The authors conclude that although noninferiority was not demonstrated, the majority of patients randomized to antibiotic treatment did not require appendectomy during the 1-year follow-up period, and those that did require appendectomy did not have serious complications.

The second study, reported in BMJ in 2012, was a meta-analysis of 4 studies in which patients (N=900) with suspected acute uncomplicated appendicitis were randomized to appendectomy or antibiotic therapy (eg, amoxicillin, cefotaxime, metronidazole, tinidazole, ofloxacin). In the antibiotic group, the authors reported a 63% success rate at 1 year and fewer complications than in the appendectomy group (relative risk reduction of 31%; Mantel-Haenszel risk ratio 0.69). Of the 470 patients treated with antibiotics, approximately 20% were readmitted for recurrence of symptoms. No significant differences were seen between treatment groups in treatment efficacy, length of hospital stay, or risk of developing complicated appendicitis. The authors conclude that antibiotics merit consideration as primary treatment in patients presenting with acute uncomplicated appendicitis.

These studies indicate that not all uncomplicated appendicitis cases progress to complicated ones, and that the majority of patients with acute uncomplicated appendicitis who are treated with antibiotic therapy have treatment success without the cost and medical risks of invasive surgery. However, these advantages need to be weighed against the approximately 20% to 30% risk of appendicitis recurrence as well as the risk of antibiotic resistance developing after the patient is treated with broad-spectrum antibiotics.

Blogger: Ginny Fleming, Founder, Lucidize Medical & Scientific Editing. Chief capacities: medical, scientific, and technical writing and editing.