Antibiotics for acute appendicitis – what is the evidence?

At morning report today, we had an interesting discussion regarding the justification of antibiotic monotherapy for acute appendicitis. The NEJM recently published a comprehensive review examining this “antibiotic first” approach. Urgent appendectomy has been the mainstay of treatment for acute appendicitis since the 1800’s. Traditionally, antibiotics have been reserved for complicated cases of appendicitis (including prolonged inflammation with phlegmon or abscess). However, recent data from the U.S. Navy as well as a series of European clinical trials suggest that antibiotic therapy alone may be appropriate for select patients. Inclusion criteria for these studies included patients that were relatively healthy without evidence of sepsis, diffuse peritonitis, abscess or perforation. Initially patients were treated with IV antibiotics targeting enteric pathogens followed by a 1-2 week course of PO antibiotics on discharge. Cross over to surgical intervention was indicated by progressive fever, intractable pain or evolution of sepsis/shock.

Clinical outcomes among patients randomly assigned to the antibiotics-first strategy were generally favorable. Patients assigned to this group had similar pain scores, required fewer doses of narcotics, and had quicker return to work. Perforation rates were not significantly higher among the antibiotic group. The rate of crossover to surgery within 48 hours after the initiation of antibiotics ranged among trials from 0 to 53%. Eventual appendectomy after initial, successful treatment with antibiotics occurred in 10 to 37% of the patients assigned to the antibiotics-first strategy (mean time to appendectomy, 4.2 to 7 months). In general, these trials viewed the antibiotic first approach as a viable option.

Despite these favorable findings, several areas of uncertainty still exist drawing caution to antibiotic monotherapy. The aforementioned trials fail to confidently assess complications related to delayed surgery, comparative cost, length of hospital stay, anxiety about future episodes of abdominal pain and factors associated with a higher risk of recurrence. Moreover, it remains unclear which patients are most appropriate for an antibiotic approach given the fact up to 50% of patients receiving monotherapy progressed to needing surgery. Furthermore, unlike the U.S. where laparascopic approach is by far most commonly performed, the majority of appendectomies included in the European trials were open. Large scale U.S. trials investigating these issues are certainly in need.

Guidlines from the American College of Surgeons, the Society for Surgery of the Alimentary Tract, and the World Society of Emergency Surgery all describe appendectomy as the treatment of choice for appendicitis. They consider antibiotic monotherapy to be potentially effective but associated with an unacceptably high rate of recurrent disease. Taken together surgical management remains standard of care in the United States. Antibiotic monotherapy can certainly be considered in select patients (those with high risk for surgery, personal aversion to invasive procedures or mild disease), but a detailed conversation regarding risks and benefits should be performed with all in consideration. Most importantly, close outpatient follow-up must be ensured in light of the significant risk for recurrent appendicitis. This topic is fascinating and clinically relevant to all internists engaged in hospital medicine.