Unresolved Questions Remain on Antibiotic Therapy In his June 2 commentary on Medscape, Dr Albert Lowenfels reviewed a meta-analysis of appendectomy and antibiotics for appendicitis and concluded that "Antibiotics may have a role to play...but there are still many unresolved questions, indicating that for now surgery will continue to be a dominant treatment strategy." As surgeon leaders of the Patient-Centered Outcomes Research Institute–funded randomized trial "Comparing Outcomes of Drugs and Appendectomy (CODA),"appendectomy. The CODA Trial Focuses on Identifying the Best Approach CODA is a noninferiority trial with a goal of randomly assigning 1552 patients at up to 16 sites of practice across the United States to either antibiotics or appendectomy for the treatment of most cases of acute appendicitis (including a 500-person observational cohort for comparison). CODA includes adult English- and/or Spanish-speaking patients with the most common type of appendicitis, excluding only those with an abscess or a phlegmon on preoperative imaging that is considered so severe that a simple appendectomy would not be recommended. Of note, patients with suspicion of perforation on preoperative imaging are being included (due to questions about the reliability of imaging in predicting perforation),[immunocompromised status and inability to undergo anesthesia means that the CODA trial should be highly generalizable. CODA includes all types of approaches to appendectomy as well as all guideline-concordant[6] antibiotic administration, including the totally outpatient use of antibiotics[7] (similar to the treatment for diverticulitis). This is considered a pragmatic trial, hopefully offering enough heterogeneity in patient type and practice setting to inform common practice. CODA focuses on both clinical outcomes and patient-reported outcomes including healthcare-related quality of life, work productivity, missed school, future healthcare burden, and decisional regret. The follow-up period is at least 2 years (and as many as 4), but we hope to evaluate patients for a longer period pending future funding. For Now, Appendectomy Should Be Considered Over Antibiotics Beyond the existing evidence gaps, there are compelling reasons to hesitate before offering antibiotics to your next patient with appendicitis. Perhaps the best reason is that appendectomy is a safe and effective procedure that is curative of the illness, with advancements in the field of anesthesia and surgery turning a disease that killed so many patients into an hour-long, often outpatient procedure. Until noninferiority (similar to equivalence) is addressed, the clinical community should hesitate to change its approach. There is also a problematic aspect of nonoperative management that CODA needs to address before antibiotics should be considered for usual care. Evaluations of appendectomy specimens reveal an approximately 1% rate of incidental neoplasm, representing tumors that may be left behind in patients treated with antibiotics. A recent review of 7970 specimens suggests that actual risk may be a bit lower than previously estimated. Unless antibiotics are being offered in the context of a research trial. While CODA is in progress (in year 2 of a 5-year study), we encourage patients and clinicians in the United States to remain open-minded about the potential value of antibiotics while at the same time not offering antibiotics for appendicitis as part of usual practice. This brings to mind the observation of Martin Buxton, emeritus professor of health economics at Brunel University, London, that "It is always too early to evaluate a technology until suddenly, it's too late." We hope that the CODA trial can evaluate the important question of noninferiority for antibiotics before this becomes the case. Source
