NIHR Signal Antibiotics may be an alternative first-line treatment for uncomplicated appendicitis
Published on 22 January 2019
Appendicectomy surgery could potentially be avoided for around 60% of adults with uncomplicated appendicitis if they receive antibiotics first.
Adults in Finland with appendicitis were randomised to have appendicectomy or a course of antibiotics. In 6 out of 10 the appendicitis settled and did not return over the five years they were followed. Of those who did go on to need surgery most did so in the first year.
If the findings from the study could be applied to the UK, it is estimated that up to 24,000 appendicectomies might be avoided in England each year.
In the UK, appendicitis is usually managed by appendicectomy, so shifting to antibiotic therapy as a first choice would require major changes in clinical practice.
- Gastrointestinal disorders, Medicines, Surgery, Acute and general medicine
Why was this study needed?
Around 40,000 people a year are admitted to hospital in England with acute appendicitis. The usual treatment for acute appendicitis (and suspected appendicitis) is removal of the appendix, to avoid the risk of rupture or sepsis.
Recent advances in diagnostic imaging mean it is now easier to diagnose uncomplicated appendicitis. This has allowed trials of other treatments, including antibiotics and observation. However, most of the trials have had relatively short follow-up, meaning some cases of recurrence of appendicitis after antibiotic treatment may have been missed.
This study intended to report on the long-term outcomes for patients enrolled on a trial of antibiotics or appendicectomy.
What did this study do?
The APPAC randomised controlled trial recruited 530 patients from six hospitals. They were aged 18 to 60 years with uncomplicated appendicitis, confirmed by CT scan. Participants were randomised to open appendicectomy (273) or antibiotics (257). Antibiotic treatment consisted of intravenous ertapentem for three days, followed by oral metronidazole (500mg three times per day) and levofloxin (500mg) for seven days.
Researchers followed patients up for five years, to see how many patients initially randomised to antibiotic treatment subsequently underwent appendicectomy. They also looked at rates of complication, hospital stay and time off work.
As surgeons could use their clinical judgement to carry out an appendicectomy in the antibiotic group if they thought it necessary, personal preference may have affected the results.
What did it find?
- The study found that 70/257 (27%) patients who initially received antibiotics had appendicectomy in the first year, 15 of them during the initial hospitalisation. In the subsequent four years, an additional 30 patients had appendicectomy. The incidence of recurrent appendicitis was 39.1% after five years (95% confidence interval [CI] 33.1 to 45.3).
- Of the 85 patients who had appendicectomy after antibiotics, 76 had uncomplicated appendicitis, two had complicated appendicitis (at least two years after the initial infection), and seven were found not to have had appendicitis at all.
- After five years, 24% (95% CI 19.2 to 30.3) of people in the surgery group and 6.5% (95% CI 3.8 to 10.4) of people in the antibiotic group had complications. Complications were defined as surgical site infections, incisional hernias, abdominal pain and obstructive symptoms.
- There were three deaths, but they were unrelated to appendicitis.
- Both groups stayed in hospital for on average three days. Average time for sick leave was 22 days for people who’d had appendicectomy, compared with 11 days after antibiotic therapy.
What does current guidance say on this issue?
Appendicectomy is the treatment of choice for appendicitis according to the 2015 NICE Clinical Knowledge Summary.
The Association of Surgeons of Great Britain and Ireland emergency general surgery guideline updated in 2017 recommends laparoscopy or imaging followed by appendicectomy for suspected appendicitis.
What are the implications?
The possibility that some of the appendicectomies carried out in the UK might be avoided by use of antibiotics is enticing. Avoiding surgery and surgical complications and reducing time off work is likely to be popular with patients.
However, a number of issues would need to be resolved before that becomes a possibility. All the people in the study had abdominal CT scans to confirm uncomplicated appendicitis while different imaging techniques may be used in the UK.
Open surgery was performed rather than the laparoscopic (keyhole) technique that is common practice in the UK, so the complication rate for surgery may be different.
Diagnostic procedures and protocols to ensure people were followed up carefully would need to be developed to ensure patient safety. Finally, there is the issue of antibiotic stewardship as ertapenem, the antibiotic used in this trial is currently reserved for severe infections.
Citation and Funding
Salminen P, Tuominen R, Paajanen H et al. Five-year follow-up of antibiotic therapy for uncomplicated acute appendicitis in the APPAC randomized clinical trial. JAMA. 2018;320(12):1259-65.
The study was funded by the Mary and Georg C Erhnrooth Foundation and Turku University.
ASGBI. Commissioning guide: Emergency general surgery (acute abdominal pain). London: Association of Surgeons of Great Britain and Ireland; 2014.
Edward H Livingston. Antibiotic treatment for uncomplicated appendicitis really works. JAMA. 2018;320(12):1245-66.
NICE. Appendicitis. Clinical Knowledge Summary. London: National Institute for Health and Clinical Excellence; 2015.
Before we consider routinely using antibiotics instead of open surgical or laparoscopic appendicectomy for uncomplicated acute appendicitis, several questions need answering.
How should we manage the 34% of antibiotic-treated patients whose appendicitis recurs within two years? What is the risk of recurrent appendicitis in the much longer term? How should we treat age groups excluded from this study (younger than 18 years or older than 60 years)? How can we avoid overlooking cancers presenting with appendicitis? Could the antibiotics be given in the community, avoiding hospital admission? And what would be the cost implications of a switch from surgical to antibiotic treatment?
David Rampton, Professor of Clinical Gastroenterology, Barts and The London School of Medicine and Dentistry
The commentator declares no conflicting interests