Many thanks to Sheila and Ron Bonaguro for hosting, and to Catherine, Kasia, Katie B, Erin, Jen B and Lindsay for their excellent discussion of the articles.
As background, there have been numerous low quality studies published dating back to 1959 raising the question of treating acute appendicitis with antibiotics rather than surgery. This journal club analyzed a meta-analysis of 4 studies (Varadhan), a Cochrane systemic review of 5 studies (Wilms) and probably the best original study on the topic (Vons). Surgery is not without risk, and the goal of JC was to evaluate if available literature supports antibiotics as a safe, curative strategy for acute appendicitis. NB, all literature discussed dealt only with adult patients.
Overall Bottom Line: The strategy of primary antibiotic treatment appears safe, and may obviate the need for surgery in some patients with acute appendicitis, but at least a quarter of patients will still go on to need surgery within the next year. Consensus in the room was that for healthy adults, surgery is the preferred treatment. One contrarian (EK) prefers antibiotics. For a subset of patients who are poor surgical risks, it would be reasonable to engage the patient/family in patient centered decision making regarding the option for antibiotic treatment.
Future: there are 2 ongoing prospective trials of antibiotics for appendicitis (APPAC and NOTA), which will likely provide higher quality data down the road.
1. Varadhan KK, Neal KR, Lobo DN: Safety and efficacy of antibiotics compared with appendicectomy for treatment of uncomplicated acute appendicitis : meta-analysis of randomised controlled trials. BMJ 2012; 2156:1–15.
This meta-analysis illustrates the “garbage in-garbage out” phenomenon of meta-analyses. This should be an extremely high level methodology for evaluating literature on a topic, but if the trials evaluated are low quality, then the meta-analysis conclusions will be very limited. Authors evaluated 4 RCTs, with a total of 900 patients (approx half who received antibiotics and half surgery), and concluded that antibiotics are both “effective and safe as primary treatment for patients with uncomplicated acute appendicitis.” While the antibiotic strategy appeared safe with regards to complications such as perforation, peritonitis and wound infection, 37% of patients receiving antibiotics ultimately required surgery for appendicitis within the following year...not so effective. One issue with the studies was the variable (or no) imaging used to diagnose appendicitis, calling into question the accuracy of the diagnosis of appendicitis. If some patients labeled appendicitis didn’t have appendicitis, antibiotics would end up looking very effective. Overall a number of comments were made about the poor quality of the included studies, including the significant cross-over between groups in one study, enrollment only of males in another, and significant followup issues. And, as Chintan pointed out, our established intervention, surgery, is safe and effective (post-op complication rate 9-11%, 10 year adhesion/obstruction rate 3%); we’re not looking for an alternative to a dangerous or inadequate intervention.
2. Wilms IM, de Hoog DE, de Visser DC, Janzing HM. Appendectomy versus antibiotic treatment for acute appendicitis. Cochrane Database Systemic Review. 2011;11(11).
So, a plug for Cochrane reviews. They are usually very high quality, and include a “plain language summary” which provides a quick and dirty conclusion about the topic. In this review of 5 RCTs/quasi RCTs on antibiotics for acute appendicitis, they performed a non-inferiority analysis to evaluate if antibiotics are as effective as surgery in acute appendicitis. It included some of the same trials as the meta-analysis. Total of 901 patients; 73% of patients treated with antibiotics compared to 97% of patients receiving surgery were cured within 2 weeks without major complications at one year. Study quality was low to moderate, with variability in diagnostic evaluation and use of prophylactic antibiotics. Due to the pre-defined non-inferiority margin and overlap of confidence intervals for the outcome measures between the 2 groups, their conclusion is that surgery remains the standard treatment for acute appendicitis. Antibiotics might be ethically studied as a treatment arm in a RCT, or considered in specific patients where surgery is contraindicated.
Side note about non inferiority analysis....these are often performed in drug company trials as the need is only to show that a new treatment is as effective or at least only marginally less effective than the old treatment. A rather arbitrary margin of non-inferiority is defined by the investigators. Burden of proof is less than in superiority trials. For more details, please see Dr. Burns.
3. Vons C, Barry C, Maitre S, Pautrat K, Leconte M, Costaglioli B, et al. Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial. Lancet 2011; 377(9777):1573–9.
This non-inferiority RCT enrolled 243 adults with acute uncomplicated appendicitis at 6 university hospitals and randomized them to surgery or augmentin x 8 days. The study was included in both the meta-analysis and the Cochrane review, and is probably the best single trial out there. All patients received CT scan for diagnosis. Primary outcome was post-intervention peritonitis within 30 days of treatment, and occurred in 8% of the antibiotic group versus 2% of the surgery group. In the antibiotic group, 26% of patients had recurrence of appendicitis and required appendectomy between 1 month and 1 year. Authors concluded that antibiotics were not non-inferior to appendectomy for acute appendicitis, and that surgery remains the gold standard treatment for acute uncomplicated appendicitis. There were no significant differences between the 2 groups for postintervention complications. Interestingly, presence of fecalith was predictive both of complicated appendicitis in surgery patients as well as antibiotic failure in the medical group (fecalith = bad). Plenty of issues with this study as well-no discussion of timing of surgery, all surgery patients also received pre-op antibiotics, and 18% of patients diagnosed with “uncomplicated appendicitis” by CT in the surgery group had complicated appendicitis with peritonitis identified in the OR. One year followup was missing for 10% of patients.