Objective To determine whether total exposure to penicillin V can be reduced while maintaining adequate clinical efficacy when treating pharyngotonsillitis caused by group A streptococci.
Design Open label, randomised controlled non-inferiority study.
Setting 17 primary healthcare centres in Sweden between September 2015 and February 2018.
Participants Patients aged 6 years and over with pharyngotonsillitis caused by group A streptococci and three or four Centor criteria (fever ≥38.5°C, tender lymph nodes, coatings of the tonsils, and absence of cough).
Interventions Penicillin V 800 mg four times daily for five days (total 16 g) compared with the current recommended dose of 1000 mg three times daily for 10 days (total 30 g).
Main outcome measures Primary outcome was clinical cure five to seven days after the end of antibiotic treatment. The non-inferiority margin was prespecified to 10 percentage points. Secondary outcomes were bacteriological eradication, time to relief of symptoms, frequency of relapses, complications and new tonsillitis, and patterns of adverse events.
Results Patients (n=433) were randomly allocated to the five day (n=215) or 10 day (n=218) regimen. Clinical cure in the per protocol population was 89.6% (n=181/202) in the five day group and 93.3% (n=182/195) in the 10 day group (95% confidence interval −9.7 to 2.2). Bacteriological eradication was 80.4% (n=156/194) in the five day group and 90.7% (n=165/182) in the 10 day group. Eight and seven patients had relapses, no patients and four patients had complications, and six and 13 patients had new tonsillitis in the five day and 10 day groups, respectively. Time to relief of symptoms was shorter in the five day group. Adverse events were mainly diarrhoea, nausea, and vulvovaginal disorders; the 10 day group had higher incidence and longer duration of adverse events.
Conclusions Penicillin V four times daily for five days was non-inferior in clinical outcome to penicillin V three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci. The number of relapses and complications did not differ between the two intervention groups. Five day treatment with penicillin V four times daily might be an alternative to the currently recommended 10 day regimen.
Trial registration EudraCT 2015-001752-30; ClinicalTrials.gov NCT02712307.

目的确定治疗A群链球菌引起的咽扁桃体炎时，能否在保持足够临床疗效的同时，减少青霉素V的总暴露量。
设计开放标签、随机对照非劣效性研究。2015 年 9 月至 2018 年 2 月期间在瑞典
设立17 个初级医疗保健中心。
参与者6 岁及以上的 A 组链球菌引起的咽扁桃体炎患者，符合三或四项 Centor 标准（发烧≥38.5°C、淋巴结触痛、扁桃体涂层、并且没有咳嗽）。
干预青霉素 V 800 mg 每天 4 次，共 5 天（共 16 g），而目前推荐的剂量为 1000 mg，每天 3 次，共 10 天（共 30 g）。
主要结局指标主要结局是抗生素治疗结束后 5 至 7 天的临床治愈。非劣效性界限预先设定为 10 个百分点。次要结果是细菌学根除、症状缓解时间、复发频率、并发症和新发扁桃体炎，以及不良事件的模式。
结果患者 (n=433) 被随机分配到 5 天 (n=215) 或 10 天 (n=218) 方案。按照方案人群的临床治愈率为 5 天组 89.6% (n=181/202) 和 10 天组 93.3% (n=182/195)（95% 置信区间 -9.7 至 2.2）。5 天组的细菌学根除率为 80.4% (n=156/194)，10 天组为 90.7% (n=165/182)。5天和10天组分别有8例和7例患者复发，无患者和4例患者出现并发症，6例和13例患者出现新发扁桃体炎。五天组的症状缓解时间更短。不良事件主要是腹泻、恶心和外阴阴道疾病；10 天组的不良事件发生率更高，持续时间更长。
结论在 A 组链球菌引起的咽扁桃体炎患者中，青霉素 V 每天 4 次共 5 天的临床结果不劣于青霉素 V 每天 3 次共 10 天。两个干预组之间的复发和并发症数量没有差异。每天四次使用青霉素 V 进行五天治疗可能是目前推荐的 10 天治疗方案的替代方案。
试验注册EudraCT 2015-001752-30；ClinicalTrials.gov NCT02712307。