Antibiotics Alone for Acute Uncomplicated Appendicitis: Ready for Prime Time?

Reviewed by Erica Stohs, MD, MPH; University of Nebraska Medical Center

Nonoperative management with antibiotics alone can be a safe and effective alternative to appendectomy for uncomplicated acute appendicitis. While appendicitis classically was referred to our surgical colleagues for routine appendectomy, newer studies challenge that age-old tradition, revealing that many cases may be successfully managed with antibiotics alone. Not only that, investigators also asked if oral antibiotics alone may do the trick.  A series of highlighted trials here specifically look at the target population of uncomplicated acute appendicitis, which require high diagnostic accuracy by CT.

In 2015, JAMA presented results from the Appendicitis Acuta (APPAC) trial, a multicenter, noninferiority randomized clinical trial in Finland, which enrolled 530 patients aged 18-60 years with uncomplicated acute appendicitis. They randomized patients to open appendectomy versus antibiotic therapy (ertapenem for 3 days followed by 7 days of oral levofloxacin and metronidazole) and followed them for one year. One quarter (27%) of those receiving antibiotics alone ultimately required appendectomy within the year, which did not meet their prespecified noninferiority margin of 24%. 

This January in JAMA, the APPAC trial group built on the premise of nonoperative management, asking: Is treatment with oral antibiotics alone noninferior to a combination of IV and oral antibiotics for treatment of CT-confirmed uncomplicated acute appendicitis? This randomized clinical trial among 599 patients compared a 7-day course of oral moxifloxacin versus combination ertapenem for 2 days followed by 5 days of oral levofloxacin and metronidazole. Treatment success (no recurrent appendicitis within 1 year) was 70% for the oral antibiotics only group compared to 74% for the IV plus oral antibiotics group. While both groups met their primary endpoint of treatment success (>65%), the oral antibiotic group failed to demonstrate noninferiority.

Antibiotic stewards can challenge the choice of antibiotics utilized in the APPAC trials – why use a carbapenem instead of ceftriaxone plus metronidazole or piperacillin-tazobactam as initial IV antibiotics? Oral moxifloxacin is not ideal from a cost or stewardship point of view either. However, other trials examining nonoperative management of uncomplicated appendicitis utilize IDSA recommended guidelines for intraabdominal infections with similar treatment success rates. What remains unaddressed are complications of antibiotic treatment, including drug-resistance and incidence of C. difficile infections.

Are antibiotics alone the preferred management for uncomplicated appendicitis? Not quite. Are antibiotics alone a safe and effective alternative to appendectomy for uncomplicated appendicitis? In 2021, the growing consensus appears to be yes. Having options is helpful and the ultimate decision for an individual patient must involve shared decision-making. Although these trials were started before the COVID-19 pandemic, the flexibility of antibiotic-only management strategies could be critical during the pandemic, freeing up hospital capacity and limiting COVID-19 exposures within the hospital. More importantly, our patients will appreciate another viable option if they are not enthusiastic about facing the surgeon’s blade. 


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