急性呼吸道感染:初級醫療中應用生物標記物導引抗生素處方的新策略

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研究表明,使用C反應蛋白(CRP)等生物標記物作為現場快速檢測(POCT),可以指導急性呼吸道感染(ARI)患者在初級醫療中的抗生素治療。評估6項試驗(3284名參與者)發現,與標準護理相比,CRP POCT可以減少抗生素的使用,但對臨床恢復無明顯差異。然而,其中一項研究顯示CRP組住院率略有增加,這可能需要進一步研究。

生物標記作為點護理測試,用於指導初級保健中急性呼吸道感染患者的抗生素處方。

Biomarkers as point-of-care tests to guide prescription of antibiotics in patients with acute respiratory infections in primary care

Aabenhus R, Jensen JU, Jørgensen KJ, Hróbjartsson A, Bjerrum L. Biomarkers as point-of-care tests to guide prescription of antibiotics in patients with acute respiratory infections in primary care. Cochrane Database Syst Rev. 2014 Nov 6;(11):CD010130. doi: 10.1002/14651858.CD010130.pub2. Update in: Cochrane Database Syst Rev. 2022 Oct 17;10:CD010130. PMID: 25374293.

https://pubmed.ncbi.nlm.nih.gov/25374293/

摘要

背景:急性呼吸道感染(ARI)是基層醫療中處方抗生素最常見的原因,儘管大多數ARI的病因是病毒性或非嚴重的細菌性。不必要的抗生素使用在許多情況下對患者的康復沒有益處,並使他們暴露於潛在的副作用。此外,由於抗生素使用與抗生素抗藥性之間存在因果關係,減少不必要的抗生素使用是控制這一重要問題的關鍵。抗生素抗藥性對醫療服務造成越來越大的負擔,並使患者面臨未來治療無效的風險,從而增加了感染性疾病的發病率和死亡率。減少基層醫療中抗生素使用的一種策略是使用感染的即時診療生物標記物來指導抗生素治療。感染的即時診療生物標記物是急性組織損傷(感染、創傷和炎症)急性階段反應的一部分,並可能在正確的臨床背景下作為感染的替代標記,有助於醫生臨床管理ARI。目標:評估在基層醫療環境中出現急性呼吸道感染症狀的患者使用即時診療生物標記物測試來指導抗生素治療的益處和危害,無論年齡如何。搜索方法:我們搜索了CENTRAL(2013年,第12期)、MEDLINE(1946年至2014年1月)、EMBASE(2010年至2014年1月)、CINAHL(1981年至2014年1月)、Web of Science(1955年至2014年1月)和LILACS(1982年至2014年1月)。選擇標準:我們納入了在基層醫療中有ARI的患者進行的隨機對照試驗(RCT),這些試驗將使用即時診療生物標記物與標準護理進行了比較。我們納入了對個別患者以及患者群體進行隨機化的試驗(群體RCT)。兩位審查作者獨立提取了以下結果數據:i)對抗生素使用的影響;ii)感染的持續時間和康復;iii)併發症,包括再諮詢次數、

住院和死亡率;iv)患者滿意度。我們評估了所有納入試驗的偏見風險,並應用了GRADE。當可行時,我們使用隨機效應的統合分析。我們進一步在預先指定的個別RCT和群體RCT亞組中分析了高度異質性的結果。

主要結果:目前在基層醫療中可用的唯一感染即時診療生物標記物是C反應蛋白。我們納入了六項評估C反應蛋白即時診療測試的試驗(3284名參與者;139名兒童)。可用的資訊來自於風險從低到中等的試驗,這些試驗解決了本次審查的主要目標。總體上發現,在C反應蛋白組中抗生素治療的使用減少了(631/1685),而標準護理組則為(785/1599)。然而,高度的異質性和對三個RCT和三個群體RCT亞組差異的統計學上顯著測試表明,對抗生素使用的統合分析結果應謹慎解釋,並且合併效應估計(風險比率(RR)0.78,95%置信區間(CI)0.66至0.92;I2統計量= 68%)可能沒有意義。我們預先計劃的基於研究設計的亞組分析中觀察到的異質性消失了:RCT的RR為0.90,95%CI為0.80至1.02;I2統計量= 5%,而群體RCT的RR為0.68,95%CI為0.61至0.75;I2統計量= 0%,這表明這是觀察到的異質性的原因。在臨床康復(定義為第7天和第28天至少有顯著改善或第28天需要再諮詢)方面,使用C反應蛋白即時診療測試與標準護理之間沒有差異。然而,我們注意到在一項研究中C反應蛋白組的住院人數增加,但這是基於少數事件,可能是偶然發現。在所有納入的研究中都沒有報告死亡。我們根據GRADE將證據質量分類為中等,因為主要效應估計的不確定性。

作者結論:用於指導基層醫療中ARI抗生素治療的即時診療

生物標記物(例如C反應蛋白)可以減少抗生素的使用,儘管減少的程度仍不確定。作為醫生臨床檢查的輔助手段,這種減少抗生素使用並未影響患者報告的結果,包括疾病的康復和持續時間。然而,住院人數可能增加的情況令人關注。需要更精確的效應估計來評估干預的成本,並將即時診療生物標記物的使用與其他節約抗生素的策略進行比較。

Abstract

Background Acute respiratory infections (ARIs) are by far the most common reason for prescribing an antibiotic in primary care, even though the majority of ARIs are of viral or non-severe bacterial aetiology. Unnecessary antibiotic use will, in many cases, not be beneficial to the patients’ recovery and expose them to potential side effects. Furthermore, as a causal link exists between antibiotic use and antibiotic resistance, reducing unnecessary antibiotic use is a key factor in controlling this important problem. Antibiotic resistance puts increasing burdens on healthcare services and renders patients at risk of future ineffective treatments, in turn increasing morbidity and mortality from infectious diseases. One strategy aiming to reduce antibiotic use in primary care is the guidance of antibiotic treatment by use of a point-of-care biomarker. A point-of-care biomarker of infection forms part of the acute phase response to acute tissue injury regardless of the aetiology (infection, trauma and inflammation) and may in the correct clinical context be used as a surrogate marker of infection,possibly assisting the doctor in the clinical management of ARIs.Objectives To assess the benefits and harms of point-of-care biomarker tests of infection to guide antibiotic treatment in patients presenting with symptoms of acute respiratory infections in primary care settings regardless of age.Search methods We searched CENTRAL (2013, Issue 12), MEDLINE (1946 to January 2014), EMBASE (2010 to January 2014), CINAHL (1981 to January 2014), Web of Science (1955 to January 2014) and LILACS (1982 to January 2014).Selection criteria We included randomised controlled trials (RCTs) in primary care patients with ARIs that compared use of point-of-care biomarkers with standard of care. We included trials that randomised individual patients as well as trials that randomised clusters of patients(cluster-RCTs).Two review authors independently extracted data on the following outcomes: i) impact on antibiotic use; ii) duration of and recovery from infection; iii) complications including the number of re-consultations, hospitalisations and mortality; iv) patient satisfaction. We assessed the risk of bias of all included trials and applied GRADE. We used random-effects meta-analyses when feasible. We further analysed results with a high level of heterogeneity in pre-specified subgroups of individually and cluster-RCTs.Main results The only point-of-care biomarker of infection currently available to primary care identified in this review was C-reactive protein. We included six trials (3284 participants; 139 children) that evaluated a C-reactive protein point-of-care test. The available information was from trials with a low to moderate risk of bias that address the main objectives of this review.Overall a reduction in the use of antibiotic treatments was found in the C-reactive protein group (631/1685) versus standard of care(785/1599). However, the high level of heterogeneity and the statistically significant test for subgroup differences between the three RCTs and three cluster-RCTs suggest that the results of the meta-analysis on antibiotic use should be interpreted with caution and the pooled effect estimate (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.66 to 0.92; I2 statistic = 68%) may not be meaningful.The observed heterogeneity disappeared in our pre planned subgroup analysis based on study design: RR 0.90, 95% CI 0.80 to 1.02; I2 statistic = 5% for RCTs and RR 0.68, 95% CI 0.61 to 0.75; I2 statistic = 0% for cluster-RCTs, suggesting that this was the cause of the observed heterogeneity.There was no difference between using a C-reactive protein point-of-care test and standard care in clinical recovery (defined as at least substantial improvement at day 7 and 28 or need for re-consultations day 28). However, we noted an increase in hospitalisations in the C-reactive protein group in one study, but this was based on few events and may be a chance finding. No deaths were reported in any of the included studies.We classified the quality of the evidence as moderate according to GRADE due to imprecision of the main effect estimate.Authors’ conclusions A point-of-care biomarker (e.g. C-reactive protein) to guide antibiotic treatment of ARIs in primary care can reduce antibiotic use,although the degree of reduction remains uncertain. Used as an adjunct to a doctor’s clinical examination this reduction in antibiotic use did not affect patient-reported outcomes, including recovery from and duration of illness.However, a possible increase in hospitalisations is of concern. A more precise effect estimate is needed to assess the costs of the intervention and compare the use of a point-of-care biomarker to other antibiotic-saving strategies.