Background

PCR-based testing has transformed the management of suspected respiratory viral infections. We aimed to determine whether multiplex bacterial PCR of bronchoalveolar lavage fluid aids antibiotic stewardship in patients with pneumonia.

Methods

This investigator-initiated, multicentre, randomised controlled trial was conducted at two tertiary care centres in Switzerland (University Hospital of Basel and Kantonsspital St Gallen). Patients aged 18 years or older who were admitted to hospital with suspected pneumonia, had a clinical indication for bronchoscopy with bronchoalveolar lavage, and were at risk of Gram-negative bacterial infection were included. Patients were randomly assigned (1:1) to either the multiplex bacterial PCR group or the conventional microbiology control group using a random allocation sequence. Treating physicians were not masked, but the committee panel was masked to patient randomisation. All patients underwent bronchoscopy with bronchoalveolar lavage and samples were assessed by conventional microbiological culture (and additionally, in the PCR group, by multiplex bacterial PCR for Gram-negative rods using the Unyvero Hospitalized Pneumonia [HPN] Cartridge; Curetis, Holzgerlingen, Germany). Patients received empirical antibiotic therapy as clinically indicated by the treating physician. In the PCR group, a recommendation regarding antibiotic therapy was made approximately 5 h after taking the sample. The primary outcome was the time in hours on inappropriate antibiotic therapy from bronchoscopy to discharge or to 30 days after bronchoscopy. This trial was registered with the International Clinical Trials Registry Platform, ISRCTN95828556.

Findings

Between May 31, 2017, and Sept 25, 2019, 740 patients with pneumonia were screened for eligibility and 208 were included and randomly assigned to the PCR group (n=100) or conventional microbiology control group (n=108). The mean age of patients was 65·9 years (SD 14·0) and 135 (65%) were male. After daily follow-up until hospital discharge or for a maximum of 30 days, the duration of inappropriate antibiotic treatment was significantly shorter by 38·6 h (95% CI 19·5–57·7) in the PCR group than in the control group (adjusted mean 47·1 h [34·7–59·5] vs 85·7 h [78·8–95·6]; p<0·0001), which translates as a decrease in the duration of inappropriate antibiotic therapy of 45·0% (37·9–52·1). Adverse events due to antimicrobial therapy occurred in nine patients (five [5%] in the PCR group vs four [4%] in the control group) and due to bronchoscopy occurred in four patients (two [1%] vs two [1%]). There were eight (8%) deaths in the PCR group and 11 (10%) in the control group. All in-hospital deaths were attributed to a respiratory cause.

Interpretation

Multiplex bacterial PCR examination of bronchoalveolar lavage decreases the duration of inappropriate antibiotic therapy of patients admitted to hospital with pneumonia and at risk of Gram-negative rod infection. This approach warrants further consideration in future antibiotic stewardship strategies.

Funding

Curetis and the Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel, Switzerland.

中文翻译：

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支气管肺泡灌洗液的快速多重细菌 PCR 用于有革兰氏阴性细菌感染风险的住院肺炎患者的抗生素管理（旗舰 II）：一项多中心、随机对照试验

背景

基于 PCR 的检测改变了疑似呼吸道病毒感染的管理方式。我们旨在确定支气管肺泡灌洗液的多重细菌 PCR 是否有助于肺炎患者的抗生素管理。

方法

这项由研究者发起的多中心随机对照试验在瑞士的两个三级医疗中心（巴塞尔大学医院和 Kantonsspital St Gallen）进行。年龄在 18 岁或以上、因疑似肺炎入院、有支气管镜检查和支气管肺泡灌洗的临床适应症、以及有革兰氏阴性细菌感染风险的患者被纳入研究。使用随机分配序列将患者随机分配 (1:1) 到多重细菌 PCR 组或常规微生物学对照组。治疗医师没有蒙面，但委员会小组对患者随机分组蒙面。所有患者均接受支气管镜检查和支气管肺泡灌洗，并通过常规微生物培养评估样本（此外，在 PCR 组中，通过使用 Unyvero 住院肺炎 [HPN] 试剂盒对革兰氏阴性杆菌进行多重细菌 PCR；Curetis，Holzgerlingen，德国）。患者接受治疗医师临床指示的经验性抗生素治疗。在 PCR 组中，在取样后大约 5 小时提出了关于抗生素治疗的建议。主要结果是从支气管镜检查到出院或到支气管镜检查后 30 天的不适当抗生素治疗的时间（以小时为单位）。该试验已在国际临床试验注册平台 ISRCTN95828556 注册。在取样后大约 5 小时提出了关于抗生素治疗的建议。主要结果是从支气管镜检查到出院或到支气管镜检查后 30 天的不适当抗生素治疗的时间（以小时为单位）。该试验已在国际临床试验注册平台 ISRCTN95828556 注册。在取样后大约 5 小时提出了关于抗生素治疗的建议。主要结果是从支气管镜检查到出院或到支气管镜检查后 30 天的不适当抗生素治疗的时间（以小时为单位）。该试验已在国际临床试验注册平台 ISRCTN95828556 注册。

发现

在 2017 年 5 月 31 日至 2019 年 9 月 25 日期间，对 740 名肺炎患者进行了合格筛查，其中 208 名患者被纳入并随机分配到 PCR 组（n=100）或常规微生物学对照组（n=108）。患者的平均年龄为 65·9 岁（SD 14·0），其中男性 135 人（65%）。每日随访至出院或最长 30 天后，PCR 组不适当抗生素治疗的持续时间显着短于对照组 38·6 h (95% CI 19·5-57·7)组（调整后的平均 47·1 小时 [34·7–59·5] vs 85·7 小时 [78·8–95·6]；p<0·0001），这意味着不适当抗生素的持续时间减少45·0% (37·9–52·1) 的治疗。9 名患者发生了由抗菌药物治疗引起的不良事件（PCR 组 5 名 [5%] vs对照组中有 4 名 [4%]），并且由于支气管镜检查在 4 名患者中发生（2 名 [1%]对2 名 [1%]）。PCR 组有 8 人（8%）死亡，对照组有 11 人（10%）死亡。所有住院死亡均归因于呼吸系统原因。

解释

支气管肺泡灌洗液的多重细菌 PCR 检查可缩短因肺炎入院且有革兰氏阴性杆菌感染风险的患者不适当抗生素治疗的持续时间。这种方法值得在未来的抗生素管理策略中进一步考虑。

资金

Curetis 和瑞士巴塞尔大学医院呼吸内科和肺细胞研究诊所。