The NOTA Study (Non Operative Treatment for Acute Appendicitis): prospective study on the efficacy and safety of antibiotics (amoxicillin and clavulanic acid) for treating patients with right lower quadrant abdominal pain and long-term follow-up of conservatively treated suspected appendicitis

Ann Surg. 2014 Jul;260(1):109-17. doi: 10.1097/SLA.0000000000000560.


Objectives: To assess the safety and efficacy of antibiotics treatment for suspected acute uncomplicated appendicitis and to monitor the long term follow-up of non-operated patients.

Background: Right lower quadrant abdominal pain is a common cause of emergency department admission. The natural history of acute appendicitis nonoperatively treated with antibiotics remains unclear.

Methods: In 2010, a total of 159 patients [mean AIR (Appendicitis Inflammatory Response) score = 4.9 and mean Alvarado score = 5.2] with suspected appendicitis were enrolled and underwent nonoperative management (NOM) with amoxicillin/clavulanate. The follow-up period was 2 years.

Results: Short-term (7 days) NOM failure rate was 11.9%. All patients with initial failures were operated within 7 days. At 15 days, no recurrences were recorded. After 2 years, the overall recurrence rate was 13.8% (22/159); 14 of 22 patients were successfully treated with further cycle of amoxicillin/clavulanate. No major side effects occurred. Abdominal pain assessed by the Numeric Rating Scale and the visual analog scale; median Numeric Rating Scale score was 3 at 5 days and 2 after 7 days. Mean length of stay of nonoperatively managed patients was 0.4 days, and mean sick leave period was 5.8 days. Long-term efficacy of NOM treatment was 83% (118 patients recurrence free and 14 patients with recurrence nonoperatively managed). None of the single factors forming the Alvarado or AIR score were independent predictors of failure of NOM or long-term recurrence. Alvarado and AIR scores were the only independent predictive factors of NOM failure after multivariate analysis, but both did not correlate with recurrences. Overall costs of NOM and antibiotics were &OV0556;316.20 per patient.

Conclusions: Antibiotics for suspected acute appendicitis are safe and effective and may avoid unnecessary appendectomy, reducing operation rate, surgical risks, and overall costs. After 2 years of follow-up, recurrences of nonoperatively treated right lower quadrant abdominal pain are less than 14% and may be safely and effectively treated with further antibiotics.

Trial registration: NCT01096927.

Publication types

  • Multicenter Study
  • Observational Study
  • Randomized Controlled Trial

MeSH terms

  • Abdominal Pain / diagnosis
  • Abdominal Pain / therapy*
  • Acute Disease
  • Adult
  • Aged
  • Amoxicillin / therapeutic use*
  • Anti-Bacterial Agents / therapeutic use
  • Appendectomy
  • Appendicitis / diagnosis
  • Appendicitis / therapy*
  • Clavulanic Acid / therapeutic use*
  • Diagnosis, Differential
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Recurrence
  • Time Factors
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Clavulanic Acid
  • Amoxicillin

Associated data