ORIGINAL ARTICLE

C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations

Christopher C. Butler, David Gillespie, Patrick White, et al

N Engl J Med 2019; 381:111-120
DOI: 10.1056/NEJMoa1803185

Abstract

BACKGROUND 背景

Point-of-care testing of C-reactive protein (CRP) may be a way to reduce unnecessary use of antibiotics without harming patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD).

床旁C反应蛋白(CRP)检测可能减少COPD急性加重(AECOPD)患者不必要的抗生素使用，同时也不造成危害

METHODS 方法

We performed a multicenter, open-label, randomized, controlled trial involving patients with a diagnosis of COPD in their primary care clinical record who consulted a clinician at 1 of 86 general medical practices in England and Wales for an acute exacerbation of COPD. The patients were assigned to receive usual care guided by CRP point-of-care testing (CRP-guided group) or usual care alone (usual-care group). The primary outcomes were patient-reported use of antibiotics for acute exacerbations of COPD within 4 weeks after randomization (to show superiority) and COPD-related health status at 2 weeks after randomization, as measured by the Clinical COPD Questionnaire, a 10-item scale with scores ranging from 0 (very good COPD health status) to 6 (extremely poor COPD health status) (to show noninferiority).

我们进行了一项多中心、开放标签、随机对照试验，在英格兰和威尔士的86个全科医疗中心纳入诊断为AECOPD的患者。患者接受随机分组，分别接受床旁CRP检测指导的常规治疗（CRP指导组）或常规治疗（常规治疗组）。主要预后指标为随机分组后4周内患者报告的因AECOPD的抗生素使用情况（优效）以及随机分组后2周时COPD相关健康状况（非劣效），后者通过临床COPD问卷评价，这是一个包括10项问题的评分，分值从0分（COPD健康状况极佳）到6分（COPD健康状况极差）。

RESULTS 结果

A total of 653 patients underwent randomization. Fewer patients in the CRP-guided group reported antibiotic use than in the usual-care group (57.0% vs. 77.4%; adjusted odds ratio, 0.31; 95% confidence interval [CI], 0.20 to 0.47). The adjusted mean difference in the total score on the Clinical COPD Questionnaire at 2 weeks was −0.19 points (two-sided 90% CI, −0.33 to −0.05) in favor of the CRP-guided group. The antibiotic prescribing decisions made by clinicians at the initial consultation were ascertained for all but 1 patient, and antibiotic prescriptions issued over the first 4 weeks of follow-up were ascertained for 96.9% of the patients. A lower percentage of patients in the CRP-guided group than in the usual-care group received an antibiotic prescription at the initial consultation (47.7% vs. 69.7%, for a difference of 22.0 percentage points; adjusted odds ratio, 0.31; 95% CI, 0.21 to 0.45) and during the first 4 weeks of follow-up (59.1% vs. 79.7%, for a difference of 20.6 percentage points; adjusted odds ratio, 0.30; 95% CI, 0.20 to 0.46). Two patients in the usual-care group died within 4 weeks after randomization from causes considered by the investigators to be unrelated to trial participation.

共有653名患者接受随机分组。与常规治疗组相比，CRP指导组更少患者报告使用抗生素（57.0% vs. 77.4%；校正后比数比，0.31; 95%可信区间[CI], 0.20 to 0.47）。2周时，两组患者临床COPD问卷总分校正后平均差为−0.19分（双侧90% CI, −0.33 to −0.05），CRP指导组更低。除1名患者外，所有患者在最初就诊时，临床医生处方抗生素的情况均已明确，96.9%的患者最初4周随访期间的抗生素处方情况也已明确。与常规治疗组相比，最初就诊时（47.7% vs. 69.7%，差异为22.0个百分点；校正后比数比，0.31；95% CI, 0.21 to 0.45）以及最初4周随访期间（59.1% vs. 79.7%，差异为20.6个百分点；校正后比数比，0.30; 95% CI, 0.20 to 0.46），CRP指导组更少患者使用抗生素。随机分组后4周内，常规治疗组2名患者死亡，研究者判断死因与参加临床试验无关。

CONCLUSIONS 结论

CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm.

在全科医疗诊所采用CRP指导抗生素处方，能够减少AECOPD患者报告的抗生素使用，同时减少使用临床医生处方抗生素的患者比例，且没有造成危害的证据。

(Funded by the National Institute for Health Research Health Technology Assessment Program; PACE Current Controlled Trials number, ISRCTN24346473.)

[评论]（仅代表个人观点）

这不是针对危重病患者的研究，但对我们或许有一些提示。受这个研究的启发，是否会有研究者针对可疑感染的ICU患者，比较CRP和PCT指导抗生素治疗的差异？

需要回答的临床问题可能包括：

• 目前临床PCT检测是否过滥？
• 生物标志物（PCT，CRP）真的能够指导抗生素治疗吗？
• 在指导抗生素治疗方面，PCT真的优于CRP吗？PCT真的优于临床判断吗？
• 在社区获得性下呼吸道感染患者得到的结论能否适用于危重病患者？