- Appendicitis
- The appendix is a slender tube connected to the end of the cecum (image of the appendix). The appendix is most known for its propensity to become inflamed, infected, and swollen. The cause of appendicitis is largely unknown, but in some cases, a stone (also called appendicolith) is present, and it is thought to precipitate appendicitis by occluding the lumen and creating pressure. An inflamed and swollen appendix can rupture, causing bacteria to spill into the peritoneal cavity. It may also form an abscess. Appendicitis is a life-threatening condition.
- For over a century, the standard of care for treating appendicitis has been surgical removal of the appendix (appendectomy). This standard predates the discovery of antibiotics, and until recently, antibiotic-only treatment of appendicitis had not been studied in trials.
- Three randomized controlled trials have now been performed that evaluated the use of antibiotics to treat appendicitis in adults. Two cohort studies have also been published that compared antibiotics to appendectomy in children. All of these studies are reviewed below.
- The CODA study enrolled 1552 adults presenting to the ER with acute appendicitis confirmed by imaging
Main inclusion criteria
- Age ≥ 18 years
- Acute appendicitis confirmed on imaging
Main exclusion criteria
- Septic shock
- Diffuse peritonitis
- Evidence of severe phlegmon on imaging
- Walled-off abscess
- Free air or more than minimal free fluid
Baseline characteristics
- Average age 38 years
- Male sex - 63%
- Average duration of symptoms - 1.7 days
- Presence of appendicolith - 27%
Randomized treatment groups
- Group 1 (776 patients): IV antibiotics for at least 24 hours followed by 10 days of oral antibiotics
- Group 2 (776 patients): Surgical appendectomy
- Most common antibiotic regimens used for IV therapy were one of the following:
- Ertapenem
- Cefoxitin
- Metronidazole + ceftriaxone, cefazolin, or levofloxacin
- Most common antibiotics used for oral therapy were metronidazole plus either ciprofloxacin or cefdinir
- Patients in the antibiotic group were discharged from the emergency department after they had received intravenous antibiotics for 24 hours or with 24 hours of bioavailability. Standard discharge criteria included intake of liquids without difficulty, adequate pain control, and an improving clinical condition.
Primary outcome: 30-day health status, as assessed with the use of the European Quality of Life–5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status). Minimal clinically important difference was predetermined to be 0.05 points.
Results
| Duration: 90 days | |||
| Outcome | Antibiotics | Appendectomy | Comparisons |
|---|---|---|---|
| Primary outcome | 0.92 | 0.91 | diff 0.01 (−0.001 to 0.03) |
|
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Findings: For the treatment of appendicitis, antibiotics were noninferior to appendectomy on
the basis of results of a standard health-status measure. In the antibiotics group,
nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants
with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith.
- A study published in the JAMA enrolled 530 patients who presented to the ER with acute appendicitis
Main inclusion criteria
- 18 - 60 years old
- Acute uncomplicated appendicitis confirmed with CT scan
Main exclusion criteria
- Complicated appendicitis defined as presence of an appendicolith, perforation, abscess, or suspicion of a tumor on the CT scan
- Peritonitis
- Serious systemic illness
Baseline characteristics
- Average age 34 years
- Male sex - 62%
- Duration of symptoms: 1-6 hours - 6% | 6-12 hours - 13% | 12-18 hours - 22% | >18 hours - 58%
Randomized treatment groups
- Group 1 (273 patients) - Open surgical appendectomy
- Group 2 (257 patients) - Ertapenem 1 gram IV once daily for 3 days followed by 7 days of levofloxacin 500 mg once daily + metronidazole 500 mg three times a day
- Patients in Group 1 received a one-time prophylactic dose of 1.5 g of cefuroxime + 500 mg of metronidazole before surgery. After that, antibiotics were only given for wound infections.
Primary outcome: for patients in the antibiotic group, the primary outcome was resolution of acute appendicitis, resulting in discharge from
the hospital without the need for surgical intervention and no recurrent appendicitis during a minimum follow-up of 1 year. For the surgical group, the primary outcome was successful appendectomy.
Results
| Duration: 1 year |
|
Findings: Among patients with CT-proven, uncomplicated appendicitis, antibiotic treatment did not meet the prespecified criterion for noninferiority compared
with appendectomy. Most patients randomized to antibiotic treatment for uncomplicated appendicitis did not require appendectomy during the 1-year follow-up period, and those who required
appendectomy did not experience significant complications.
- Patients in the original study detailed above were followed for 5 years total and results were published in 2018
- In the antibiotic group, 39% (85 patients) of patients underwent appendectomy by the end of 5 years. Of these 85 patients, 76 had uncomplicated appendicitis, 2 had complicated appendicitis, and 7 did not have appendicitis
- Complications (surgical site infections, incisional hernias, abdominal pain, and obstructive symptoms) occurred more frequently in the appendectomy group (24.4%) than in the antibiotic group (6.5%)
Findings: Among patients who were initially treated with antibiotics for uncomplicated acute appendicitis, the likelihood of late recurrence within 5 years was
39.1%. This long-term follow-up supports the feasibility of antibiotic treatment alone as an alternative to surgery for uncomplicated acute appendicitis.
- The APPAC II trial enrolled 599 adults with acute uncomplicated appendicitis
Main inclusion criteria
- Age 18 - 60 years
- Uncomplicated appendicitis on CT scan
Main exclusion criteria
- Presence of appendicolith
- Perforation
- Abscess
- Suspicion of tumor
- Renal insufficiency
Baseline characteristics
- Average age 36 years
- Female sex - 44%
- Median duration of symptoms - 20 hours
- Average appendiceal diameter - 10.8 mm
Randomized treatment groups
- Group 1 (301 patients): Oral moxifloxacin 400 mg once daily for 7 days
- Group 2 (298 patients): IV ertapenem sodium 1000 mg once daily X 2 days followed by oral levofloxacin 500 mg once daily + metronidazole 500 mg three times a day for 5 days
- The first dose of the randomized treatment was given in the ER. Patients followed up at the hospital in 20 - 24 hours, and patients randomized to IV therapy were given their second dose.
- The clinical condition of the patient was evaluated twice daily, approximately 12 hours after admission by the on-call surgeon. If the patient was suspected of not responding to the antibiotic therapy, the patient underwent laparoscopic appendectomy based on the surgeon’s decision.
Primary outcome: Treatment success at 1 year, defined as resolution of acute appendicitis resulting in discharge from the hospital without the need for surgical intervention and no recurrent appendicitis during the 1-year follow-up
Results
| Duration: 1 year | |||
| Outcome | Moxifloxacin | Ertapenem + Levo/Metro | Comparisons |
|---|---|---|---|
| Primary outcome | 70% | 73.8% | p=0.26 |
| Length of primary hospital stay | 28.9 hours | 29.9 hours | p=0.38 |
| Overall mortality | 0% | 0% | N/A |
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Findings: Among adults with uncomplicated acute appendicitis, treatment with 7 days of oral moxifloxacin compared with 2 days of intravenous ertapenem followed by 5 days of levofloxacin and metronidazole resulted in treatment success rates
greater than 65% in both groups, but failed to demonstrate noninferiority for treatment success of oral antibiotics compared with intravenous followed by oral antibiotics.
- STUDY
- Design: Prospective patient-choice cohort study (N=1068 | length = 1 year) in children 7 - 17 years old with uncomplicated appendicitis
- Treatment: Patient and caregiver choice between antibiotics (piperacillin-tazobactam or ciprofloxacin + metronidazole) or urgent (≤ 12 hours of admission) laparoscopic appendectomy
- Primary outcomes: The 2 primary outcomes assessed at 1 year were average number of disability days, defined as the total number of days the child was not able to participate in all of his/her normal activities secondary to appendicitis-related care, and success rate of nonoperative management, defined as the proportion of patients initially managed nonoperatively who did not undergo appendectomy by 1 year
- Results:
- Disability days: Antibiotics - 6.6, Surgery - 10.9 (p<0.001)
- Success rate (no appendectomy at 1 year): Antibiotics - 67.1%
- 25% of participants were lost during follow-up
- Findings: Among children with uncomplicated appendicitis, an initial nonoperative management strategy with antibiotics alone had a success rate of 67.1% and, compared with urgent surgery, was associated with statistically significantly fewer disability days at 1 year. However, there was substantial loss to follow-up, the comparison with the prespecified threshold for an acceptable success rate of nonoperative management was not statistically significant, and the hypothesized difference in disability days was not met.
- STUDY
- Design: Cohort study (N=102, length = 1 year) in patients aged 7 - 17 years presenting to the ER with uncomplicated appendicitis
- Treatment: Parent choice between appendectomy or antibiotics (65 chose appendectomy while 37 chose antibiotics)
- Primary outcome: One-year success rate of nonoperative management with success defined as not having undergone an appendectomy at 1 year
- Results:
- In the antibiotic group, 75.7% (95%CI [59% - 88%]) of patients achieved the primary outcome (28 out of 37)
- The incidence of complicated appendicitis was 2.7% in the antibiotic group and 12.3% in the appendectomy group
- The median number of disability days was 8 in the antibiotic group and 21 in the appendectomy group (p<0.001)
- Patients in the antibiotic group received piperacillin–tazobactam or (if allergic) ciprofloxacin + metronidazole IV for a minimum of 24 hours. When tolerating a regular diet, patients were switched to oral amoxicillin–clavulanate or ciprofloxacin + metronidazole to complete a 10-day course.
- Findings: When chosen by the family, nonoperative management is an effective treatment strategy for children with uncomplicated acute appendicitis, incurring less morbidity and lower costs than surgery.
- SUMMARY
- The two randomized controlled trials that compared appendectomy to antibiotics found that about 60 - 70% of patients with acute, uncomplicated appendicitis can be treated successfully with antibiotics. In the CODA trial, the presence of an appendicolith was associated with worse outcomes in the antibiotic group.
- In the APPAC II trial, oral moxifloxacin for 7 days was 70% effective in treating uncomplicated appendicitis. This is quite remarkable when one considers the cost difference between surgical appendectomy and a 7-day prescription of moxifloxacin.
- The cohort studies found that 67 - 76% of children did fine with antibiotic treatment. Patients were not randomized, so it is possible that participants who chose antibiotic therapy were healthier and less ill than those in the appendectomy group. This makes the results of these trials less substantial.
- In summary, it appears that about 60 - 70% of patients with uncomplicated appendicitis can be successfully treated with antibiotics. Patients with an appendicolith do better with surgery.