Key messages
– Medicine that kills bacteria (antibiotics) may result in unsuccessful treatment of symptoms for a few people.
– Antibiotics may reduce wound infection but increase time spent at the hospital slightly.
– One third of people with appendicitis initially treated with antibiotics underwent surgery for appendicitis within one year. Put another way, two-thirds of people avoided surgery within one year.
What is appendicitis?
Appendicitis (painful swelling in the finger-shaped pouch that protrudes from the intestine) is a common condition. People experience pain in the middle and right part of the tummy.
How is appendicitis treated?
In the past, surgery with removal of the finger-shaped pouch (called appendectomy) was thought to be the only treatment for this condition, but appendicitis may also be treated with a medicine that kills bacteria (antibiotics).
What did we want to find out?
We wanted to find out if antibiotics were better than surgery for people with appendicitis. We were interested in the effect of antibiotics on how long people lived, and how antibiotics improved their tummy pain. We also wanted to find out if antibiotics were associated with any unwanted effects or consequences.
What did we do?
We searched medical databases for studies that looked at treatment with antibiotics compared with surgery in adults. We compared and summarised the results of these studies, and we rated our confidence in the evidence based on factors such as study methods and sizes.
What did we find?
We found 13 studies that involved 3358 people with appendicitis. The studies were mainly conducted in Asia, Europe, and North America, and they lasted from a few days to seven years. Two studies received funding from companies that made the medicines. The types of antibiotics used were those that kill a wide range of bacteria in the intestine. Surgery was mainly performed as key-hole surgery.
Main results
Antibiotics may have little to no effect on deaths, but we are very uncertain about the results. We could not make any firm conclusions on complications as we have little confidence in the evidence. Antibiotics may slightly increase unsuccessful treatment of symptoms, meaning that 76 out of every 1000 people will still have symptoms after antibiotics compared with surgery. Antibiotics may slightly reduce wound infections. Time spent in the hospital increased slightly by half a day after antibiotics. Almost one-third of people given antibiotics needed surgery within the first year (or two-thirds avoided surgery), but we are very uncertain about the results.
What are the limitations of the evidence?
We generally have little confidence in most of the evidence because people in the studies were aware of which treatment they were getting, some studies used a different type of surgery other than key-hole, and the evidence was based on a low number of cases for death and complications.
How up to date is the evidence?
This review updates our previous review. The evidence is up to date to July 2022.
Antibiotics may be associated with higher rates of unsuccessful treatment for 76 per 1000 people, although differences may not be clinically significant. It is uncertain if antibiotics increase length of hospital stay by half a day. Antibiotics may reduce wound infections. A third of the participants initially treated with antibiotics required subsequent appendectomy or two-thirds avoided surgery within one year, but the evidence is very uncertain. There were too few data from the included studies to comment on major complications.
Acute appendicitis is one of the most common emergency general surgical conditions worldwide. Uncomplicated/simple appendicitis can be treated with appendectomy or antibiotics. Some studies have suggested possible benefits with antibiotics with reduced complications, length of hospital stay, and the number of days off work. However, surgery may improve success of treatment as antibiotic treatment is associated with recurrence and future need for surgery.
To assess the effects of antibiotic treatment for uncomplicated/simple acute appendicitis compared with appendectomy for resolution of symptoms and complications.
We searched CENTRAL, MEDLINE, Embase, and two trial registers (World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov) on 19 July 2022. We also searched for unpublished studies in conference proceedings together with reference checking and citation search. There were no restrictions on date, publication status, or language of publication.
We included parallel-group randomised controlled trials (RCTs) only. We included studies where most participants were adults with uncomplicated/simple appendicitis. Interventions included antibiotics (by any route) compared with appendectomy (open or laparoscopic).
We used standard methodology expected by Cochrane. We used GRADE to assess the certainty of evidence for each outcome. Primary outcomes included mortality and success of treatment, and secondary outcomes included number of participants requiring appendectomy in the antibiotic group, complications, pain, length of hospital stay, sick leave, malignancy in the antibiotic group, negative appendectomy rate, and quality of life. Success of treatment definitions were heterogeneous although mainly based on resolution of symptoms rather than incorporation of long-term recurrence or need for surgery in the antibiotic group.
We included 13 studies in the review covering 1675 participants randomised to antibiotics and 1683 participants randomised to appendectomy. One study was unpublished. All were conducted in secondary care and two studies received pharmaceutical funding. All studies used broad-spectrum antibiotic regimens expected to cover gastrointestinal bacteria. Most studies used predominantly laparoscopic surgery, but some included mainly open procedures. Six studies included adults and children. Almost all studies aimed to exclude participants with complicated appendicitis prior to randomisation, although one study included 12% with perforation. The diagnostic technique was clinical assessment and imaging in most studies. Only one study limited inclusion by sex (male only). Follow-up ranged from hospital admission only to seven years. Certainty of evidence was mainly affected by risk of bias (due to lack of blinding and loss to follow-up) and imprecision.
Primary outcomes
It is uncertain whether there was any difference in mortality due to the very low-certainty evidence (Peto odds ratio (OR) 0.51, 95% confidence interval (CI) 0.05 to 4.95; 1 study, 492 participants). There may be 76 more people per 1000 having unsuccessful treatment in the antibiotic group compared with surgery, which did not reach our predefined level for clinical significance (risk ratio (RR) 0.91, 95% CI 0.87 to 0.96; I2 = 69%; 7 studies, 2471 participants; low-certainty evidence).
Secondary outcomes
At one year, 30.7% (95% CI 24.0 to 37.8; I2 = 80%; 9 studies, 1396 participants) of participants in the antibiotic group required appendectomy or, alternatively, more than two-thirds of antibiotic-treated participants avoided surgery in the first year, but the evidence is very uncertain. Regarding complications, it is uncertain whether there is any difference in episodes of Clostridium difficile diarrhoea due to very low-certainty evidence (Peto OR 0.97, 95% CI 0.24 to 3.89; 1 study, 1332 participants). There may be a clinically significant reduction in wound infections with antibiotics (RR 0.25, 95% CI 0.09 to 0.68; I2 = 16%; 9 studies, 2606 participants; low-certainty evidence). It is uncertain whether antibiotics affect the incidence of intra-abdominal abscess or collection (RR 1.58, 95% CI 0.61 to 4.07; I2 = 19%; 6 studies, 1831 participants), or reoperation (Peto OR 0.13, 95% CI 0.01 to 2.16; 1 study, 492 participants) due to very low-certainty evidence, mainly due to rare events causing imprecision and risk of bias. It is uncertain if antibiotics prolonged length of hospital stay by half a day due to the very low-certainty evidence (MD 0.54, 95% CI 0.06 to 1.01; I2 = 97%; 11 studies, 3192 participants). The incidence of malignancy was 0.3% (95% CI 0 to 1.5; 5 studies, 403 participants) in the antibiotic group although follow-up was variable. Antibiotics probably increased the number of negative appendectomies at surgery (RR 3.16, 95% CI 1.54 to 6.49; I2 = 17%; 5 studies, 707 participants; moderate-certainty evidence).