A prospective randomized controlled multicenter trial comparing antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis (APPAC trial) Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial. A role for conservative antibiotic treatment in early appendicitis in children. Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial A National Evaluation of the Conservative Management of Uncomplicated Acute Appendicitis: How Common Is This and What Are the Issues?
Background Although the st and ard treatment of acute appendicitis ( AA ) consists of an early appendectomy , there has recently been both an interest and an increase in the use of antibiotic therapy as the primary treatment for uncomplicated AA . However , the use of antibiotic therapy in the treatment of uncomplicated AA is still controversial . Methods / design The APPAC trial is a r and omized prospect i ve controlled , open label , non-inferiority multicenter trial design ed to compare antibiotic therapy ( ertapenem ) with emergency appendectomy in the treatment of uncomplicated AA . The primary endpoint of the study is the success of the r and omized treatment . In the antibiotic treatment arm successful treatment is defined as being discharged from the hospital without the need for surgical intervention and no recurrent appendicitis during a minimum follow-up of one-year ( treatment efficacy ) . Treatment efficacy in the operative treatment arm is defined as successful appendectomy evaluated to be 100 % . Secondary endpoints are post-intervention complications , overall morbidity and mortality , the length of hospital stay and sick leave , treatment costs and pain scores ( VAS , visual analoque scale ) . A maximum of 610 adult patients ( aged 18–60 years ) with a CT scan confirmed uncomplicated AA will be enrolled from six hospitals and r and omized by a closed envelope method in a 1:1 ratio either to undergo emergency appendectomy or to receive ertapenem ( 1 g per day ) for three days continued by oral levofloxacin ( 500 mg per day ) plus metronidazole ( 1.5 g per day ) for seven days . Follow-up by a telephone interview will be at 1 week , 2 months and 1 , 3 , 5 and 10 years ; the primary and secondary endpoints of the trial will be evaluated at each time point . Discussion The APPAC trial aims to provide level I evidence to support the hypothesis that approximately 75–85 % of patients with uncomplicated AA can be treated with effective antibiotic  therapy avoiding unnecessary appendectomies and the related operative morbidity , also result ing in major cost savings . Trial registration Clinical IMPORTANCE An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis . OBJECTIVE To compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography ( CT ) . DESIGN , SETTING , AND PARTICIPANTS The Appendicitis Acuta ( APPAC ) multicenter , open-label , noninferiority r and omized clinical trial was conducted from November 2009 until June 2012 in Finl and . The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan . Patients were r and omly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period . INTERVENTIONS Patients r and omized to antibiotic therapy received intravenous ertapenem ( 1 g/d ) for 3 days followed by 7 days of oral levofloxacin ( 500 mg once daily ) and metronidazole ( 500 mg 3 times per day ) . Patients r and omized to the surgical treatment group were assigned to undergo st and ard open appendectomy . MAIN OUTCOMES AND MEASURES The primary end point for the surgical intervention was the successful completion of an appendectomy . The primary end point for antibiotic-treated patients was discharge from the hospital without the need for surgery and no recurrent appendicitis during a 1-year follow-up period . RESULTS There were 273 patients in the surgical group and 257 in the antibiotic group . Of 273 patients in the surgical group , all but 1 underwent successful appendectomy , result ing in a success rate of 99.6 % ( 95 % CI , 98.0 % to 100.0 % ) . In the antibiotic group , 70 patients ( 27.3 % ; 95 % CI , 22.0 % to 33.2 % ) underwent appendectomy within 1 year of initial presentation for appendicitis . Of the 256 patients available for follow-up in the antibiotic group , 186 ( 72.7 % ; 95 % CI , 66.8 % to 78.0 % ) did not require surgery . The intention-to-treat analysis yielded a difference in treatment efficacy between groups of -27.0 % ( 95 % CI , -31.6 % to ∞ ) ( P = .89 ) . Given the prespecified noninferiority margin of 24 % , we were unable to demonstrate noninferiority of antibiotic treatment relative to surgery . Of the 70 patients r and omized to antibiotic treatment who subsequently underwent appendectomy , 58 ( 82.9 % ; 95 % CI , 72.0 % to 90.8 % ) had uncomplicated appendicitis , 7 ( 10.0 % ; 95 % CI , 4.1 % to 19.5 % ) had complicated acute appendicitis , and 5 ( 7.1 % ; 95 % CI , 2.4 % to 15.9 % ) did not have appendicitis but received appendectomy for suspected recurrence . There were no intra-abdominal abscesses or other major complications associated with delayed appendectomy in patients r and omized to antibiotic treatment . CONCLUSIONS AND RELEVANCE Among patients with CT-proven , uncomplicated appendicitis , antibiotic treatment did not meet the prespecified criterion for noninferiority compared with appendectomy . Most patients r and omized 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 . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01022567 PURPOSE To evaluate whether antibiotics without surgery is sufficient treatment for children with clinical ly and ultrasonographically suspected acute appendicitis ( AA ) . METHOD Children with clinical , laboratory and radiological findings suspicious for AA were evaluated prospect ively . Patients with mild clinical signs , without peritonitis were considered for IV followed by oral antibiotics without surgery . RESULTS From 1 November 2013 through 30 June 2014 , 45 children were diagnosed with early , acute appendicitis . Ages ranged from 4 to 15 years ( mean 9.3 ) and 32 ( 75 % ) were boys . All had routine , clinical laboratory and ultrasound workup . Forty-two improved with antibiotic treatment and were discharged home within 3 - 5 days , without surgery . Three of them were operated on within 24 hours , another two underwent appendectomy for recurrent appendicitis : one at 2 weeks and the other 2 months after discharge . There was no more recurrent appendicitis in 6 - 14-month follow-up . CONCLUSION Our series of patients with AA treated with antibiotics only are a product of the observation that some children improve with antibiotics alone at a stage in which surgery is still debatable . These results ( 89 % success rate ) support the conservative approach in cases of early appendicitis , without increased morbidity in failed cases 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 r and omized clinical trial comparing appendectomy with antibiotic therapy , in which 530 patients aged 18 to 60 years with computed tomography – confirmed uncomplicated acute appendicitis were r and omized to undergo an appendectomy ( n = 273 ) or receive antibiotic therapy ( n = 257 ) . The initial trial was conducted from November 2009 to June 2012 in Finl and ; 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 r and omized to undergo appendectomy , and 257 ( median age , 33 years , [ IQR , 26 - 47 ] ) were r and omized 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 Clinical Trials.gov Identifier : Introduction : The management approach for acute appendicitis has been challenged in recent years , with numerous r and omized controlled trials demonstrating that antibiotics/conservative management is an efficacious treatment , with lower complication rates . Methods : A national survey of all consultant general surgeons evaluating their practice s was performed . Reasons for changed practice s , choice of antibiotics and follow-up investigations were evaluated . In addition , the role of interval appendicectomy and conservative management in the pediatric population was also assessed . Results : The response rate for this survey was 74.7 % ( n = 74/99 ) . Over one-fifth ( n = 17 , 22.9 % ) routinely treat acute appendicitis conservatively , while another 14.8 % ( n = 11 ) consider this approach in selected cases . Main reasons for modified practice s included the presence of inflammatory phlegmon ( 75 % ) , delayed presentation ( 64 % ) , and recent evidence -based medicine developments ( 46 % ) . Co-amoxiclav/clavulanic acid was the most popular antibiotic for conservative management ( 53 % ) . Alternatively , combinations of antibiotics were also utilized . One-third felt interval appendicectomy was warranted , while one-fifth supported conservative management in the paediatric setting . The overwhelming majority ( > 95 % ) advocate follow-up colonoscopy ± computed tomography in any patient aged > 40 years managed conservatively . Conclusion : Considerable variation in management of uncomplicated appendicitis  remains in Irel and despite growing evidence suggesting that the non-operative approach is safe . Reasons for adopting a conservative management practice have been identified and reflect the exp and ing literature on this subject
With significantly higher efficacy and low complication rates , appendectomy remains the most effective treatment for patients with uncomplicated AA .
BACKGROUND Acute appendicitis is the most common surgical diagnosis in young patients , with lifetime prevalence of about 7 % .
Debate remains on whether uncomplicated AA should be operated or not .
Aim of this meta- analysis of r and omized controlled trials was to assess current evidence on antibiotic treatment for uncomplicated AA compared to st and ard surgical treatment .