ImportanceCurrent short-term evidence has shown that uncomplicated acute appendicitis can be treated successfully with oral antibiotics alone, but longer-term results are lacking.ObjectiveTo assess the treatment effectiveness of oral antibiotic monotherapy compared with combined intravenous (IV) and oral antibiotics in computed tomography–confirmed uncomplicated acute appendicitis at a longer-term follow-up.Design, Setting, and ParticipantsThis secondary analysis of a predefined year 3 follow-up of the Appendicitis Acuta II (APPAC II) noninferiority, multicenter randomized clinical trial compared oral moxifloxacin with combined IV ertapenem plus oral levofloxacin and metronidazole for the treatment of uncomplicated acute appendicitis. The trial was conducted at 9 university and central hospitals in Finland from April 2017 to November 2018, with the last follow-up in November 2022. Participants included patients aged 18 to 60 years, who were randomized to receive either oral antibiotics monotherapy (n = 301) or combined IV and oral antibiotics (n = 298).InterventionsAntibiotics monotherapy consisted of oral moxifloxacin, 400 mg/d, for 7 days. Combined IV and oral antibiotics consisted of IV ertapenem sodium, 1 g/d, for 2 days plus oral levofloxacin, 500 mg/d, and metronidazole, 500 mg 3 times/d, for 5 days.Main Outcomes and MeasuresThe primary end point was treatment success, defined as the resolution of acute appendicitis and discharge from hospital without the need for surgical intervention and no appendicitis recurrence at the year 3 follow-up evaluated using a noninferiority design. The secondary end points included late (after 1 year) appendicitis recurrence as well as treatment-related adverse events, quality of life, length of hospital stay, and length of sick leave, which were evaluated using a superiority design.ResultsAfter exclusions, 599 patients (mean [SD] age, 36 [12] years; 336 males [56.1%]) were randomized; after withdrawal and loss to follow-up, 582 patients (99.8%) were available for the year 3 follow-up. The treatment success at year 3 was 63.4% (1-sided 95% CI, 58.8% to ∞) in the oral antibiotic monotherapy group and 65.2% (1-sided 95% CI, 60.5% to ∞) in the combined IV and oral antibiotics group. The difference in treatment success rate between the groups at year 3 was −1.8 percentage points (1-sided 95% CI, −8.3 percentage points to ∞; P = .14 for noninferiority), with the CI limit exceeding the noninferiority margin. There were no significant differences between groups in treatment-related adverse events, quality of life, length of hospital stay, or length of sick leave.Conclusions and RelevanceThis secondary analysis of the APPAC II trial found a slightly higher appendectomy rate in patients who received oral antibiotic monotherapy; however, noninferiority of oral antibiotic monotherapy compared with combined IV and oral antibiotics could not be demonstrated. The results encourage future studies to assess oral antibiotic monotherapy as a viable treatment alternative for uncomplicated acute appendicitis.Trial RegistrationClinicalTrials.gov Identifier: NCT03236961

中文翻译：

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口服抗生素与静脉和口服抗生素治疗单纯性急性阑尾炎的三年结果

重要性目前的短期证据表明，单纯口服抗生素可以成功治疗无并发症的急性阑尾炎，但缺乏长期结果。目的通过计算机断层扫描评估口服抗生素单药治疗与静脉注射（IV）和口服抗生素联合治疗的治疗效果– 在长期随访中证实了无并发症的急性阑尾炎。设计、设置和参与者这项对急性阑尾炎 II (APPAC II) 的预定义第 3 年随访的二次分析是非劣效性、多中心随机临床试验，比较了口服莫西沙星与联合用药静脉注射厄他培南加口服左氧氟沙星和甲硝唑治疗无并发症的急性阑尾炎。该试验于 2017 年 4 月至 2018 年 11 月在芬兰 9 所大学和中心医院进行，最后一次随访于 2022 年 11 月。参与者包括 18 至 60 岁的患者，他们被随机接受口服抗生素单药治疗（n = 301）或联合静脉注射和口服抗生素（n = 298）。干预措施抗生素单一疗法包括口服莫西沙星，400 mg/d，持续 7 天。静脉注射和口服联合抗生素包括静脉注射厄他培南钠，1 g/d，持续 2 天，加口服左氧氟沙星，500 mg/d，甲硝唑，500 mg，3 次/d，持续 5 天。 主要终点是治疗成功，定义为急性阑尾炎消退并出院，无需手术干预，并且使用非劣效性设计评估的第 3 年随访时无阑尾炎复发。次要终点包括晚期（1年后）阑尾炎复发以及治疗相关的不良事件、生活质量、住院时间和病假时间，这些终点均采用优效性设计进行评估。结果排除后，599名患者（平均 [SD] 年龄，36 [12] 岁；336 名男性 [56.1%]）被随机分组​​；退出并失访后，582 名患者 (99.8%) 可以进行第 3 年的随访。口服抗生素单药治疗组第 3 年的治疗成功率为 63.4%（单侧 95% CI，58.8% 至 ∞），静脉注射和口服联合治疗组的治疗成功率为 65.2%（单侧 95% CI，60.5% 至 ∞）抗生素组。第 3 年时，各组之间的治疗成功率差异为 -1.8 个百分点（单侧 95% CI，-8.3 个百分点至 ∞；磷= .14（非劣效性），CI 限值超过非劣效性界限。各组之间在治疗相关不良事件、生活质量、住院时间或病假长度方面没有显着差异。 结论和相关性 APPAC II 试验的二次分析发现，接受口服药物治疗的患者阑尾切除率略高抗生素单一疗法；然而，与静脉注射和口服抗生素联合治疗相比，口服抗生素单一疗法的非劣效性无法得到证明。结果鼓励未来的研究评估口服抗生素单一疗法作为无并发症的急性阑尾炎的可行治疗替代方案。试验注册ClinicalTrials.gov标识符：NCT03236961