非ICU社区获得性肺炎患者β-内酰胺3天治疗效果不逊于8天治疗

本期文章:《柳叶刀》:Volume 397 Number 10280 法国雷蒙德庞加莱大学医院Aurélien…

本期文章:《柳叶刀》:Volume 397 Number 10280

法国雷蒙德庞加莱大学医院Aurélien Dinh团队研究了非重症监护病房(PTC)社区获得性肺炎患者3天后停止β-内酰胺治疗的临床结局。2021年3月26日,该成果发表在《柳叶刀》杂志上。

缩短社区获得性肺炎住院患者的抗生素治疗时间有助于减少抗生素消耗,从而减少细菌耐药性、不良事件和相关费用。为了评估在治疗3天后稳定的社区获得性肺炎患者是否需要额外的5天β-内酰胺疗程,研究组在法国的16个中心进行了一项双盲、随机、安慰剂对照、非劣效性试验。

研究组招募因中重度社区获得性肺炎入院(非ICU)成人患者(年龄≥18岁),且在接受β-内酰胺治疗3天后符合预先规定的临床稳定性标准,将其按1:1随机分配,分别接受β-内酰胺+克拉维酸,或匹配的安慰剂再治疗5天。主要结局是首次服用抗生素后15天痊愈,定义为无症状(体温≤37.8℃),呼吸系统症状缓解或改善,并且没有任何原因的额外抗生素治疗。

2013年12月19日至2018年2月1日,研究组对706名患者进行了资格评估,在β-内酰胺治疗3天后,310名合格患者被随机分配,其中157例接受安慰剂、153例接受β-内酰胺治疗。7名患者在服用任何研究药物前撤回同意书,5名在安慰剂组,2名在β-内酰胺组。

ITT人群的中位年龄为73.0岁,303名参与者中123名(41%)为女性。在ITT分析中,安慰剂组152名受试者中有117名(77%)在第15天治愈,β-内酰胺组151名受试者中有102名(68%),符合非劣效性标准。在按方案分析中,安慰剂组145名受试者中有113名(78%)在第15天治愈,β-内酰胺组146名受试者中有100名(68%),符合非劣效性标准。

两个治疗组的不良事件发生率相似,其中安慰剂组152例中有22例(14%),β-内酰胺组151例中有29例(19%)。最常见的不良事件是消化系统疾病,安慰剂组152例患者中有17例(11%),β-内酰胺组151例患者中有28例(19%)。到第30天,安慰剂组有3名(2%)患者死亡(1名死于金黄色葡萄球菌引起的菌血症,1名死于急性肺水肿后的心源性休克,1名死于与急性肾功能衰竭相关的心力衰竭),β-内酰胺组有2名(1%)患者死亡(死于肺炎复发和可能的急性肺水肿)。

研究结果表明,对于符合临床稳定性标准的社区获得性肺炎住院患者,3天后停止β-内酰胺治疗并不劣于8天治疗。这些发现可以大幅度减少抗生素的消耗。

附:英文原文

Title: Discontinuing β-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial

Author: Aurélien Dinh, Jacques Ropers, Clara Duran, Benjamin Davido, Laurène Deconinck, Morgan Matt, Olivia Senard, Aurore Lagrange, Sabrina Makhloufi, Guillaume Mellon, Victoire de Lastours, Frédérique Bouchand, Emmanuel Mathieu, Jean-Emmanuel Kahn, Elisabeth Rouveix, Julie Grenet, Jennifer Dumoulin, Thierry Chinet, Marion Pépin, Véronique Delcey, Sylvain Diamantis, Daniel Benhamou, Virginie Vitrat, Marie-Christine Dombret, Bertrand Renaud, Christian Perronne, Yann-Erick Claessens, José Labarère, Jean-Pierre Bedos, Philippe Aegerter, Anne-Claude Crémieux, Julie ATTAL-BEHAR, Sébastien BEAUNE, Thierry CHINET, Tristan CUDENNEC, Marine DE LAROCHE, Albane DE THEZY, Jennifer DUMOULIN, Caroline DUPONT, Elise FERCOT, Violaine GIRAUT, Ségolène GREFFE, Julie GRENET, Caroline GUYOT, Jean-Emmanuel KAHN, Sylvie LABRUNE, Marie LACHATRE, Sophie MOULIAS, Charlotte NALINE, Marion PEPIN, Elisabeth ROUVEIX, Marine SAHUT-DIZARN, Abel SEFSSAFI, Laurent TEILLET, Jean-Pierre BRU, Jacques GAILLAT, Vincent GAUTIER, Cécile JANSSEN, Leonardo PAGANI, Virginie VITRAT, Malika ABDERRAHMANE, Juliette CAMUSET, Catherine LEGALL, Pascale LONGUET-FLANDRES, Anne-Marie MENN, Victoire DE LASTOURS, Marie LECRONIER, Gwenolée PREVOST, Charles BURDET, Ouda DERRADJI, Lelia ESCAUT, Etienne HINGLAIS, Philippe LEBRAS, Edouard LEFEVRE, Mathilde NOAILLON, Pauline RABIER, Maurice RAPHAEL, Elina TEICHER, Christiane VERNY, Daniel VITTECOQ, Benjamin WYPLOSZ, Michèle BEN HAYOUN, Franoise BRUN-VEZINET, Enrique CASALINO, Christophe CHOQUET, Marie-Christine DOMBRET, Xavier DUVAL, Nadhira HOUHOU, Véronique JOLY, Xavier LESCURE, Manuela POGLIAGHI, Christophe RIOUX, Yazdan YAZDANPANAH, Elsa BARROS, Belinda BEGGA, Sébastien BOUKOBZA, Houria BOUREDJI, Imad CHOUAHI, Isabelle DELACROIX, Antoine FROISSART, Valérie GARRAIT, Elsa NGWEM, Catherine PHLIPPOTEAU, Sepehr SALEHABADI, Cécile TOPER, Florent VINAS, Marie AMSILLI, Olivier EPAULARD, Patricia PAVESE, Isabelle PIERRE, Jean-Paul STAHL, Jérme AULAGNIER, Julie CELERIER, Roxana COJOCARIU, Emmanuel MATHIEU, Charlotte RACHLINE, Yoland SCHOINDRE, Thomas SENE

Issue&Volume: 2021/03/27

Abstract:

Background

Shortening the duration of antibiotic therapy for patients admitted to hospital with community-acquired pneumonia should help reduce antibiotic consumption and thus bacterial resistance, adverse events, and related costs. We aimed to assess the need for an additional 5-day course of β-lactam therapy among patients with community-acquired pneumonia who were stable after 3 days of treatment.

Methods

We did this double-blind, randomised, placebo-controlled, non-inferiority trial (the Pneumonia Short Treatment [PTC]) in 16 centres in France. Adult patients (aged ≥18 years) admitted to hospital with moderately severe community-acquired pneumonia (defined as patients admitted to a non-critical care unit) and who met prespecified clinical stability criteria after 3 days of treatment with β-lactam therapy were randomly assigned (1:1) to receive β-lactam therapy (oral amoxicillin 1 g plus clavulanate 125 mg three times a day) or matched placebo for 5 extra days. Randomisation was done using a web-based system with permuted blocks with random sizes and stratified by randomisation site and Pneumonia Severity Index score. Participants, clinicians, and study staff were masked to treatment allocation. The primary outcome was cure 15 days after first antibiotic intake, defined by apyrexia (temperature ≤37·8°C), resolution or improvement of respiratory symptoms, and no additional antibiotic treatment for any cause. A non-inferiority margin of 10 percentage points was chosen. The primary outcome was assessed in all patients who were randomly assigned and received any treatment (intention-to-treat [ITT] population) and in all patients who received their assigned treatment (per-protocol population). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT01963442, and is now complete.

Findings

Between Dec 19, 2013, and Feb 1, 2018, 706 patients were assessed for eligibility, and after 3 days of β-lactam treatment, 310 eligible patients were randomly assigned to receive either placebo (n=157) or β-lactam treatment (n=153). Seven patients withdrew consent before taking any study drug, five in the placebo group and two in the β-lactam group. In the ITT population, median age was 73·0 years (IQR 57·0–84·0) and 123 (41%) of 303 participants were female. In the ITT analysis, cure at day 15 occurred in 117 (77%) of 152 participants in the placebo group and 102 (68%) of 151 participants in the β-lactam group (between-group difference of 9·42%, 95% CI 0·38 to 20·04), indicating non-inferiority. In the per-protocol analysis, 113 (78%) of 145 participants in the placebo treatment group and 100 (68%) of 146 participants in the β-lactam treatment group were cured at day 15 (difference of 9·44% [95% CI 0·15 to 20·34]), indicating non-inferiority. Incidence of adverse events was similar between the treatment groups (22 [14%] of 152 in the placebo group and 29 [19%] of 151 in the β-lactam group). The most common adverse events were digestive disorders, reported in 17 (11%) of 152 patients in the placebo group and 28 (19%) of 151 patients in the β-lactam group. By day 30, three (2%) patients had died in the placebo group (one due to bacteraemia due to Staphylococcus aureus, one due to cardiogenic shock after acute pulmonary oedema, and one due to heart failure associated with acute renal failure) and two (1%) in the β-lactam group (due to pneumonia recurrence and possible acute pulmonary oedema).

Interpretation

Among patients admitted to hospital with community-acquired pneumonia who met clinical stability criteria, discontinuing β-lactam treatment after 3 days was non-inferior to 8 days of treatment. These findings could allow substantial reduction of antibiotic consumption.

DOI: 10.1016/S0140-6736(21)00313-5

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00313-5/fulltext期刊信息

LANCET:《柳叶刀》,创刊于1823年。隶属于爱思唯尔出版社,最新IF:59.102

关于作者: ekarlee

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