Mini-Cat by Rochel Boord
Clinical Question:
A 15 y/o presents with appendicitis and is scheduled for surgery.
Question:
Can using antibiotics to treat appendicitis be as effective as appendectomy to treat non-perforated appendicitis?
Search Strategy:
My search involved looking for meta-analysis and systematic review because they are the highest level of evidence. After looking for meta-analysis and systematic review, I realized I needed more articles that directly addressed what I was looking for. As such I had to look for articles that were a lower level of evidence. My next best choice was randomized control trials. In randomized control trials patients are randomly be assigned to receive surgery or antibiotics to treat their appendicitis.
I searched for articles published within the last 5 years.
Outline the terms used, databases or other tools used, how many articles returned, and how you selected the final articles to base your CAT on. This will likewise be a revision and refinement of what you have already done.
| Searches conducted: |
| Pubmed Search terms: antiobiotics for uncomplicated acute appendicitis Filters: last five years, meta-analysis, systematic review Search Results: 22 results |
| Pubmed Search terms: antiobiotics versus appendectomy Filters: Last 10 years, meta-analysis Search Results: 14 |
| Pubmed Search terms: using antibiotics to treat appendicitis Date range last 5 years results 71 |
| Pubmed Search terms: using antibiotics to treat appendicitis in adults Date range last 5 years results 38 |
Articles Chosen
Article 1 Efficacy and Safety of Nonoperative Treatment for Acute Appendicitis: A Meta-analysis
https://pediatrics.aappublications.org/content/139/3/e20163003.long
Abstract
Context: Nonoperative treatment (NOT) with antibiotics alone of acute uncomplicated appendicitis (AUA) in children has been proposed as an alternative to appendectomy.
Objective: To determine safety and efficacy of NOT based on current literature.
Data sources: Three electronic databases.
Study selection: All articles reporting NOT for AUA in children.
Data extraction: Two reviewers independently verified study inclusion and extracted data.
Results: Ten articles reporting 413 children receiving NOT were included. Six, including 1 randomized controlled trial, compared NOT with appendectomy. The remaining 4 reported outcomes of children receiving NOT without a comparison group. NOT was effective as the initial treatment in 97% of children (95% confidence interval [CI] 96% to 99%). Initial length of hospital stay was shorter in children treated with appendectomy compared with NOT (mean difference 0.5 days [95% CI 0.2 to 0.8]; P = .002). At final reported follow-up (range 8 weeks to 4 years), NOT remained effective (no appendectomy performed) in 82% of children (95% CI 77% to 87%). Recurrent appendicitis occurred in 14% (95% CI 7% to 21%). Complications and total length of hospital stay during follow-up were similar for NOT and appendectomy. No serious adverse events related to NOT were reported.
Limitations: The lack of prospective randomized studies limits definitive conclusions to influence clinical practice.
Conclusions: Current data suggest that NOT is safe. It appears effective as initial treatment in 97% of children with AUA, and the rate of recurrent appendicitis is 14%. Longer-term clinical outcomes and cost-effectiveness of NOT compared with appendicectomy require further evaluation, preferably in large randomized trials, to reliably inform decision-making.
Article 2 Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial
https://pubmed.ncbi.nlm.nih.gov/30264120/
Abstract
Importance: Short-term results support antibiotics as an alternative to surgery for treating uncomplicated acute appendicitis, but long-term outcomes are not known.
Objective: To determine the late recurrence rate of appendicitis after antibiotic therapy for the treatment of uncomplicated acute appendicitis.
Design, setting, and participants: Five-year observational follow-up of patients in the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotic therapy, in which 530 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were randomized to undergo an appendectomy (n = 273) or receive antibiotic therapy (n = 257). The initial trial was conducted from November 2009 to June 2012 in Finland; last follow-up was September 6, 2017. This current analysis focused on assessing the 5-year outcomes for the group of patients treated with antibiotics alone.
Interventions: Open appendectomy vs antibiotic therapy with intravenous ertapenem for 3 days followed by 7 days of oral levofloxacin and metronidazole.
Main outcomes and measures: In this analysis, prespecified secondary end points reported at 5-year follow-up included late (after 1 year) appendicitis recurrence after antibiotic treatment, complications, length of hospital stay, and sick leave.
Results: Of the 530 patients (201 women; 329 men) enrolled in the trial, 273 patients (median age, 35 years [IQR, 27-46]) were randomized to undergo appendectomy, and 257 (median age, 33 years, [IQR, 26-47]) were randomized to receive antibiotic therapy. In addition to 70 patients who initially received antibiotics but underwent appendectomy within the first year (27.3% [95% CI, 22.0%-33.2%]; 70/256), 30 additional antibiotic-treated patients (16.1% [95% CI, 11.2%-22.2%]; 30/186) underwent appendectomy between 1 and 5 years. The cumulative incidence of appendicitis recurrence was 34.0% (95% CI, 28.2%-40.1%; 87/256) at 2 years, 35.2% (95% CI, 29.3%-41.4%; 90/256) at 3 years, 37.1% (95% CI, 31.2%-43.3%; 95/256) at 4 years, and 39.1% (95% CI, 33.1%-45.3%; 100/256) at 5 years. Of the 85 patients in the antibiotic group who subsequently underwent appendectomy for recurrent appendicitis, 76 had uncomplicated appendicitis, 2 had complicated appendicitis, and 7 did not have appendicitis. At 5 years, the overall complication rate (surgical site infections, incisional hernias, abdominal pain, and obstructive symptoms) was 24.4% (95% CI, 19.2%-30.3%) (n = 60/246) in the appendectomy group and 6.5% (95% CI, 3.8%-10.4%) (n = 16/246) in antibiotic group (P < .001), which calculates to 17.9 percentage points (95% CI, 11.7-24.1) higher after surgery. There was no difference between groups for length of hospital stay, but there was a significant difference in sick leave (11 days more for the appendectomy group).
Conclusions and relevance: 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.
Trial registration: ClinicalTrials.gov Identifier: NCT01022567.
Article 3 Antibiotics-First Versus Surgery for Appendicitis: A US Pilot Randomized Controlled Trial Allowing Outpatient Antibiotic Management
Abstract
Study objective: Randomized trials suggest that nonoperative treatment of uncomplicated appendicitis with antibiotics-first is safe. No trial has evaluated outpatient treatment and no US randomized trial has been conducted, to our knowledge. This pilot study assessed feasibility of a multicenter US study comparing antibiotics-first, including outpatient management, with appendectomy.
Methods: Patients aged 5 years or older with uncomplicated appendicitis at 1 US hospital were randomized to appendectomy or intravenous ertapenem greater than or equal to 48 hours and oral cefdinir and metronidazole. Stable antibiotics-first-treated participants older than 13 years could be discharged after greater than or equal to 6-hour emergency department (ED) observation with next-day follow-up. Outcomes included 1-month major complication rate (primary) and hospital duration, pain, disability, quality of life, and hospital charges, and antibiotics-first appendectomy rate.
Results: Of 48 eligible patients, 30 (62.5%) consented, of whom 16 (53.3%) were randomized to antibiotics-first and 14 (46.7%) to appendectomy. Median age was 33 years (range 9 to 73 years), median WBC count was 15,000/μL (range 6,200 to 23,100/μL), and median computed tomography appendiceal diameter was 10 mm (range 7 to 18 mm). Of 15 antibiotic-treated adults, 14 (93.3%) were discharged from the ED and all had symptom resolution. At 1 month, major complications occurred in 2 appendectomy participants (14.3%; 95% confidence interval [CI] 1.8% to 42.8%) and 1 antibiotics-first participant (6.3%; 95% CI 0.2% to 30.2%). Antibiotics-first participants had less total hospital time than appendectomy participants, 16.2 versus 42.1 hours, respectively. Antibiotics-first-treated participants had less pain and disability. During median 12-month follow-up, 2 of 15 antibiotics-first-treated participants (13.3%; 95% CI 3.7% to 37.9%) developed appendicitis and 1 was treated successfully with antibiotics; 1 had appendectomy. No more major complications occurred in either group.
Conclusion: A multicenter US trial comparing antibiotics-first to appendectomy, including outpatient management, is feasible to evaluate efficacy and safety.
Article 4 Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis
https://pubmed.ncbi.nlm.nih.gov/26990957/
Abstract
Background: For more than a century, appendicectomy has been the treatment of choice for appendicitis. Recent trials have challenged this view. This study assessed the benefits and harms of antibiotic therapy compared with appendicectomy in patients with non-perforated appendicitis.
Methods: A comprehensive search was conducted for randomized trials comparing antibiotic therapy with appendicectomy in patients with non-perforated appendicitis. Key outcomes were analysed using random-effects meta-analysis, and the quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Results: Five studies including 1116 patients reported major complications in 25 (4·9 per cent) of 510 patients in the antibiotic and 41 (8·4 per cent) of 489 in the appendicectomy group: risk difference -2·6 (95 per cent c.i. -6·3 to 1·1) per cent (low-quality evidence). Minor complications occurred in 11 (2·2 per cent) of 510 and 61 (12·5 per cent) of 489 patients respectively: risk difference -7·2 (-18·1 to 3·8) per cent (very low-quality evidence). Of 550 patients in the antibiotic group, 47 underwent appendicectomy within 1 month: pooled estimate 8·2 (95 per cent c.i. 5·2 to 11·8) per cent (high-quality evidence). Within 1 year, appendicitis recurred in 114 of 510 patients in the antibiotic group: pooled estimate 22·6 (15·6 to 30·4) per cent (high-quality evidence). For every 100 patients with non-perforated appendicitis, initial antibiotic therapy compared with prompt appendicectomy may result in 92 fewer patients receiving surgery within the first month, and 23 more experiencing recurrent appendicitis within the first year.
Conclusion: The choice of medical versus surgical management in patients with clearly uncomplicated appendicitis is value- and preference-dependent, suggesting a change in practice towards shared decision-making is necessary.
Summary of the Evidence:
| Author (Date) | Level of Evidence | Sample/Setting (# of subjects/ studies, cohort definition etc. ) | Outcome(s) studied | Key Findings | Limitations and Biases |
| Georgiou R, Eaton S, Stanton MP, Pierro A, Hall NJ. Efficacy and Safety of Nonoperative Treatment for Acute Appendicitis: A Meta-analysis. Pediatrics. 2017 Mar;139(3):e20163003. doi: 10.1542/peds.2016-3003. Epub 2017 Feb 17. PMID: 28213607. | Meta-analysis | 413 Children | Adverse events due to non-operative therapy for appendicitis. Recurrent appendicitis and long-term efficacy of non-operative therapy for appendicitis. Comparative outcomes of non-operative therapy versus appendectomy in terms of length of hospital stay, readmission. | Non-operarative therapy has not been found to be unsafe and no studies reported adverse events due to non-operative therapy. Complications due to appendectomy or non-operative therapy are uncommon. The initial length of hospital stay was shorter in children treated with appendectomy compared with non-operative therapy (mean difference 0.5 day). Non-operative therapy for children with acute uncomplicated appendicitis is 97% effective. | This meta-analysis included data from retropspective studies, noncomparative studies and non-randomized studies. This could be bias. |
| 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 [published correction appears in JAMA. 2018 Oct 23;320(16):1711]. JAMA. 2018;320(12):1259-1265. doi:10.1001/jama.2018.13201 | Randomized clinical trial | 530 patients aged 18-60 years old | This study looked at the late recurrence rate (up to five years after the initial incidence) of appendicitis after being treated with antibiotic therapy for the treatment of uncomplicated acute appendicitis. Additionally late complications occurring in both the appendectomy group and the antibiotic therapy group were also assessed. Complications assessed included surgical site infections, incisional hernias, abdominal or incisional pain, or obstructive symptoms. Length of hospital stay and sick leave from work was also assessed. | 73% of patients treated with antibiotics for acute uncomplicated appendicitis did not require surgery after 1 year. There was a 39.1% recurrence rate within 5 years.70% of the recurrence occurred in the first year. None of the patients who were initially treated with antibiotics, and ultimately developed recurrent appendicitis, had any complications due to the delay in surgery. Seven of the 100 patients who had appendectomy didn’t actually have appendicitis. If they could have avoided surgery the actual success rate for antibiotic therapy would be 63.7%. | There is no protocol to decide who should have an appendectomy. This was decided by the discretion of the surgeon. As a result more appendectomies were likely performed due to physician bias. Some physicians were bias because they did not believe antibiotics was a reasonable treatment. Patients in this study had open surgery. If laparoscopic surgery was performed the hospital stay would have been shorter. Since antibiotics are not the standard of care patients needed to stay in the hospital after treatment with a median of 3 days, and were given broad spectrum antibiotics. |
| Talan DA, Saltzman DJ, Mower WR, et al. Antibiotics-First Versus Surgery for Appendicitis: A US Pilot Randomized Controlled Trial Allowing Outpatient Antibiotic Management. Ann Emerg Med. 2017;70(1):1-11.e9. doi:10.1016/j.annemergmed.2016.08.446 | Randomized Controlled Trial | 48 patients aged 5 years and older | This study aimed to evaluate outpatient treatment with antibiotics for appendicitis versus appendectomy in the United States. The outcomes studied included the one-month major complication rate. Major complications include organ/space infections, including peritonitis, wound dehiscence, pneumonia, unplanned intubation, pulmonary embolism, mechanical ventilation for more than 48 hours, progressive renal insufficiency, major urinary tract infection, malignant hyperthermia, strok/cerebral vascular accident, coma for more than 24 hours, cardiac arrest, myocardial infarction, bleeding requiring transfusion, severe sepsis and septic shock, deep venous thrombosis, unexpected re-operation related to appendicitis, dehydration requiring hospitalization, unplanned hospitalization related to complication of appendicitis, antibiotic related adverse events, including colitis. Secondary outcomes studied included appendectomy rate in the antibiotics-first group, quality of life, days unable to work or perform normal activities, days of analgesic use, pain socres at 24 hours before each visit, total hours in the ED and hospital, total hours in the hospital including the ED through 1 month, Alvarado scores, hospital charges. | 14/15 of the adult patients who received antibiotics first were successfully managed outpatient after a minimum 6 hour ED observation. 13.3% had recurrence of appendicitis within one year. The hospital stays were shorter than what was reported in other randomized trials. This is likely because of the way health care is practiced in Europe versus the U.S.. All major complications occurred within the first month. The antibiotics-first group had a 6.3% rate of major complications, while the appendectomy group had a 14.3% rate. The authors believe the appendectomy complication rate to be due to sampling error, because the historical complication rate after appendectomy is 5%. One third of antibiotic treated patients were pain free and back to normal activities after approximately 24 hours. | This study had a small sample size. The authors state to their knowledge this is the first randomized controlled trial for antibiotics versus appendectomy in the United States. This might be the reason they were not able to get a larger sample. |
| Sallinen V, Akl EA, You JJ, et al. Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis. Br J Surg. 2016;103(6):656-667. doi:10.1002/bjs.10147 | Systematic review and meta-analysis | 1,116 patients | This article looked at the merits of antibiotic therapy versus immediate appendectomy in patients with non-perforated appendicitis. Major complications, minor complications, recurrence of appendicitis within 1 year, duration of hospital stay, and duration of sick leave was studied. | Both antibiotics and appendectomy have their advantages and disadvantages. Antibiotics are associated with a lower rate of major complications (primarily appendiceal perforations), a potentially lower rate of minor complications, and shorter sick leave. | Three of the RTCs used made the diagnosis of appendicitis without CT.The authors didn’t report complication of antibiotics such as diarrhea or allergic reaction. Also many of the authors didn’t go into detail about the complication of appendectomy. |
Conclusion(s):
Article 1
This study was a meta-analysis and included 413 children. The study found antibiotic therapy as an initial treatment of acute appendicitis in children is safe and 97% effective. The recurrence rate is 14%. Children treated with antibiotic therapy compared to appendectomy has a shorter hospital stay.
Article 2
This randomized clinical trial included 530 participants and followed patients for five years after treatment for appendicitis. Patients who were initially treated with antibiotics for acute uncomplicated appendicitis had a 39.1% recurrence rate within 5 years. 70% of the recurrence occurred in the first year. In patients who had recurrence, there was no hard in delaying the appendectomy. This study supports the use of antibiotics for acute uncomplicated appendicitis.
Article 3
This randomized controlled trial specifically looked at the use of antibiotics versus appendectomy in the united states. This study focused on managing patients outpatient with antibiotics for appendicitis. 14/15 patients were successfully managed outpatient after a minimum 6 hour ED observation period. 13.3% of patients had recurrence. Patients treated with antibiotics had a lower rate of major complications.
Article 4
This meta-analysis looked at the benefit and harms of antibiotic therapy compared with appendicectomy in patients with non-perforated appendicitis. This study included 1,116 patients and showed antibiotics had a lower rate of major complications (primarily appendiceal perforations). Medical versus surgical management should be preference dependent and a shared decision between patient and clinician.
General Conclusion
Initial treatment of acute uncomplicated appendicitis with antibiotics is safe. Antibiotic therapy is less invasive, has a lower complication rate, shorter hospital stay and allows patients to get back to their daily routine quicker. Patients treated with antibiotics have a risk of recurrence. The recurrence is most often in the first year.
Clinical bottom line
The first article I chose was a meta-analysis and had a large sample size. This article looked only at children. My second article had a large sample size, and included patients aged 18-60. Treating patients for acute uncomplicated appendicitis with antibiotics instead of surgery is more common in Europe than in the United States. In the United States the standard is appendectomy. This made it hard to find studies conducted in the United States. I had to use foreign articles. The third article I chose has a small sample size, I chose to include it, because it took place in the United States. I also liked that it included both children and adults. The fourth article was a meta-analysis, had the largest sample size from all the articles I chose. However, the conclusion didn’t go into detail. The conclusion said both appendectomy and antibiotics have advantages and disadvantages, it then went on to mention only few of the benefits of antibiotics. Overall, all of my articles suggest that antibiotics as an initial treatment for patients with acute uncomplicated appendicitis is safe, although it is effective in most cases, there still is a risk of recurrence. The recurrence rate varied based on the study ranging from 14% – 39.1%. Most studies looked at the recurrence within one year. The second article looked at recurrence up to 5 years. 70% of the recurrences occurred within one year. Patients with recurrence don’t have a worse outcome than those treated with appendectomy initially. Antibiotics for acute appendicitis seems like a good choice, however, before I can suggest this to my patient’s further research needs to be conducted on patients living in the United States.
