Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland; Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
Lancet Respir Med. 2022 Sep;10(9):877-887. doi: 10.1016/S2213-2600(22)00086-8. Epub 2022 May 23.
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.
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.
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.
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.
Curetis and the Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel, Switzerland.
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。
这是一项由瑞士两家三级保健中心（巴塞尔大学医院和圣加仑州立医院）发起的、多中心、随机对照试验。纳入年龄在 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临床指征且有革兰氏阴性细菌感染风险的患者。采用随机分配序列将患者（1:1）随机分配至多重细菌 PCR 组或常规微生物学对照组。治疗医生未设盲，但委员会小组对患者的随机分组设盲。所有患者均接受支气管镜检查和支气管肺泡灌洗，样本通过常规微生物学培养进行评估（PCR 组还使用 Curetis（德国霍尔茨基尔兴）的 Unyvero 住院肺炎 [HPN] 试剂盒进行革兰氏阴性杆菌的多重细菌 PCR）。治疗医生根据临床指征给予经验性抗生素治疗。在 PCR 组，在取样后大约 5 小时给出关于抗生素治疗的建议。主要结局是从支气管镜检查到出院或支气管镜检查后 30 天内，不适当抗生素治疗的时间（以小时计）。该试验在国际临床试验注册平台（ISRCTN）上注册，编号为 ISRCTN95828556。
2017 年 5 月 31 日至 2019 年 9 月 25 日，对 740 名肺炎患者进行了筛选，纳入 208 名并随机分配至 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），135 名（65%）为男性。在每日随访直至出院或最长 30 天期间，PCR 组的不适当抗生素治疗时间明显缩短 38.6 小时（95%CI 19.5-57.7）（校正平均 47.1 小时[34.7-59.5] vs 85.7 小时[78.8-95.6]；p<0.0001），这相当于不适当抗生素治疗时间缩短了 45.0%（37.9-52.1）。由于抗菌治疗而发生的不良事件在 9 名患者（PCR 组 5[5%] vs 对照组 4[4%]）中发生，由于支气管镜检查而发生的不良事件在 4 名患者（PCR 组 2[1%] vs 对照组 2[1%]）中发生。PCR 组有 8 名（8%）患者死亡，对照组有 11 名（10%）患者死亡。所有院内死亡均归因于呼吸原因。
支气管肺泡灌洗液的多重细菌 PCR 检查可缩短因疑似肺炎入院且有革兰氏阴性杆菌感染风险的患者的不适当抗生素治疗时间。这种方法值得在未来的抗生素管理策略中进一步考虑。
Curetisu 和巴塞尔大学医院呼吸医学和肺细胞研究科，瑞士。
