Unit for Antibiotics and Infection Control, The Public Health Agency of Sweden, SE 171 82 Solna, Sweden
Lundbergsgatan Primary Health Care Centre, Malmö, Sweden.
BMJ. 2019 Oct 4;367:l5337. doi: 10.1136/bmj.l5337.
To determine whether total exposure to penicillin V can be reduced while maintaining adequate clinical efficacy when treating pharyngotonsillitis caused by group A streptococci.
Open label, randomised controlled non-inferiority study.
17 primary healthcare centres in Sweden between September 2015 and February 2018.
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).
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).
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.
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.
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.
EudraCT 2015-001752-30; ClinicalTrials.gov NCT02712307.
在治疗 A 组链球菌引起的咽扁桃体炎时，确定在保持足够临床疗效的同时，能否减少青霉素 V 的总暴露量。
开放标签、随机对照非劣效性研究。
2015 年 9 月至 2018 年 2 月期间瑞典的 17 个初级保健中心。
年龄 6 岁及以上、由 A 组链球菌引起咽扁桃体炎且符合 3 或 4 项 Centor 标准（发热≥38.5°C、淋巴结触痛、扁桃体覆盖物和无咳嗽）的患者。
青霉素 V 800mg 每日 4 次，共 5 天（总量 16g），与目前推荐的 1000mg 每日 3 次、共 10 天（总量 30g）的剂量相比。
主要结局为抗生素治疗结束后 5-7 天的临床治愈率。非劣效性边界预先指定为 10 个百分点。次要结局为细菌学清除率、症状缓解时间、复发频率、并发症和新的扁桃体炎以及不良事件模式。
患者（n=433）被随机分配至 5 天（n=215）或 10 天（n=218）方案。在符合方案人群中，5 天组的临床治愈率为 89.6%（n=181/202），10 天组为 93.3%（n=182/195）（95%置信区间-9.7 至 2.2）。5 天组的细菌学清除率为 80.4%（n=156/194），10 天组为 90.7%（n=165/182）。5 天组有 8 例和 7 例患者复发，无患者和 4 例患者发生并发症，5 天组和 10 天组分别有 6 例和 13 例患者发生新的扁桃体炎。5 天组症状缓解时间更短。不良事件主要为腹泻、恶心和外阴阴道疾病；10 天组不良事件的发生率更高，持续时间更长。
在 A 组链球菌引起的咽扁桃体炎患者中，青霉素 V 每日 4 次、共 5 天的治疗方案在临床结局方面不劣于青霉素 V 每日 3 次、共 10 天的治疗方案。两组干预措施之间的复发和并发症发生率没有差异。与目前推荐的 10 天疗程相比，每日 4 次、共 5 天的青霉素 V 治疗可能是一种替代方案。
EudraCT 2015-001752-30；ClinicalTrials.gov NCT02712307。
