Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC, USA; Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC, USA; Emergency Medicine Service, Durham VA Health Care System, Durham, NC, USA.
Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Lancet Infect Dis. 2023 Apr;23(4):484-495. doi: 10.1016/S1473-3099(22)00735-6. Epub 2022 Dec 13.
Lower respiratory tract infections are frequently treated with antibiotics, despite a viral cause in many cases. It remains unknown whether low procalcitonin concentrations can identify patients with lower respiratory tract infection who are unlikely to benefit from antibiotics. We aimed to compare the efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections in patients with low procalcitonin.
We conducted a randomised, placebo-controlled, double-blind, non-inferiority trial at five health centres in the USA. Adults aged 18 years or older with clinically suspected non-pneumonia lower respiratory tract infection and symptom duration from 24 h to 28 days were eligible for enrolment. Participants with a procalcitonin concentration of 0·25 ng/mL or less were randomly assigned (1:1), in blocks of four with stratification by site, to receive over-encapsulated oral azithromycin 250 mg or matching placebo (two capsules on day 1 followed by one capsule daily for 4 days). Participants, non-study clinical providers, investigators, and study coordinators were masked to treatment allocation. The primary outcome was efficacy of azithromycin versus placebo in terms of clinical improvement at day 5 in the intention-to-treat population. The non-inferiority margin was -12·5%. Solicited adverse events (abdominal pain, vomiting, diarrhoea, allergic reaction, or yeast infections) were recorded as a secondary outcome. This trial is registered with ClinicalTrials.gov, NCT03341273.
Between Dec 8, 2017, and March 9, 2020, 691 patients were assessed for eligibility and 499 were enrolled and randomly assigned to receive azithromycin (n=249) or placebo (n=250). Clinical improvement at day 5 was observed in 148 (63%, 95% CI 54 to 71) of 238 participants with full data in the placebo group and 155 (69%, 61 to 77) of 227 participants with full data in the azithromycin group in the intention-to-treat analysis (between-group difference -6%, 95% CI -15 to 2). The 95% CI for the difference did not meet the non-inferiority margin. Solicited adverse events and the severity of solicited adverse events were not significantly different between groups at day 5, except for increased abdominal pain associated with azithromycin (47 [23%, 95% CI 18 to 29] of 204 participants) compared with placebo (35 [16%, 12 to 21] of 221; between-group difference -7% [95% CI -15 to 0]; p=0·066).
Placebo was not non-inferior to azithromycin in terms of clinical improvement at day 5 in adults with lower respiratory tract infection and a low procalcitonin concentration. After accounting for both the rates of clinical improvement and solicited adverse events at day 5, it is unclear whether antibiotics are indicated for patients with lower respiratory tract infection and a low procalcitonin concentration.
National Institute of Allergy and Infectious Diseases, bioMérieux.
尽管许多情况下下呼吸道感染是由病毒引起的，但仍经常使用抗生素进行治疗。目前尚不清楚降钙素原浓度较低是否可以识别不太可能从抗生素治疗中受益的下呼吸道感染患者。我们旨在比较阿奇霉素与安慰剂在下呼吸道感染中治疗降钙素原较低的患者的疗效和安全性。
我们在美国的五个医疗中心进行了一项随机、安慰剂对照、双盲、非劣效性试验。年龄在 18 岁或以上，有临床疑似非肺炎性下呼吸道感染，症状持续时间为 24 小时至 28 天的患者有资格参加。降钙素原浓度为 0.25ng/ml 或更低的患者随机分组（1:1），按部位分层，接受包被口服阿奇霉素 250mg 或匹配安慰剂（第 1 天 2 粒，随后 4 天每天 1 粒）。参与者、非研究临床医生、研究人员和研究协调员对治疗分配进行了盲法。主要结局是阿奇霉素与安慰剂在治疗第 5 天的临床改善方面的疗效，意向治疗人群的非劣效性边界为-12.5%。记录了治疗第 5 天的不良事件（腹痛、呕吐、腹泻、过敏反应或酵母感染）。该试验在 ClinicalTrials.gov 上注册，NCT03341273。
2017 年 12 月 8 日至 2020 年 3 月 9 日，对 691 名患者进行了资格评估，有 499 名患者入选并随机分配接受阿奇霉素（n=249）或安慰剂（n=250）治疗。在安慰剂组中，238 名有完整数据的患者中，有 148 名（63%，95%CI 54-71）在治疗第 5 天观察到临床改善，227 名有完整数据的阿奇霉素组患者中，有 155 名（69%，95%CI 61-77）在治疗第 5 天观察到临床改善（组间差异-6%，95%CI-15-2）。差异的 95%CI 未达到非劣效性边界。在治疗第 5 天，除阿奇霉素组（204 名参与者中有 47 名[23%，95%CI 18-29]）与安慰剂组（221 名参与者中有 35 名[16%，12-21]）相比，腹部疼痛发生率较高外（组间差异-7%[95%CI-15-0]；p=0.066），不良事件和不良事件严重程度在两组间无显著差异。
在降钙素原浓度较低的下呼吸道感染成人中，与安慰剂相比，阿奇霉素在第 5 天的临床改善方面不具有非劣效性。在考虑了第 5 天的临床改善率和不良事件后，仍不清楚抗生素是否适用于降钙素原浓度较低的下呼吸道感染患者。
美国国立过敏和传染病研究所、生物梅里埃。
