Navapurkar Vilas, Bartholdson Scott Josefin, Maes Mailis, Hellyer Thomas P, Higginson Ellen, Forrest Sally, Pereira-Dias Joana, Parmar Surendra, Heasman-Hunt Emma, Polgarova Petra, Brown Joanne, Titti Lissamma, Smith William Pw, Scott Jonathan, Rostron Anthony, Routledge Matthew, Sapsford David, Török M Estée, McMullan Ronan, Enoch David A, Wong Vanessa, Curran Martin D, Brown Nicholas M, Simpson A John, Herre Jurgen, Dougan Gordon, Conway Morris Andrew
John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK.
Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK.
Wellcome Open Res. 2022 Oct 12;6:256. doi: 10.12688/wellcomeopenres.17099.3. eCollection 2021.
The diagnosis of pneumonia has been hampered by a reliance on bacterial cultures which take several days to return a result, and are frequently negative. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and compromises good antimicrobial stewardship. The objective of this study was to establish the performance of a syndromic molecular diagnostic approach, using a custom TaqMan array card (TAC) covering 52 respiratory pathogens, and assess its impact on antimicrobial prescribing. The TAC was validated against a retrospective multi-centre cohort of broncho-alveolar lavage samples. The TAC was assessed prospectively in patients undergoing investigation for suspected pneumonia, with a comparator cohort formed of patients investigated when the TAC laboratory team were unavailable. Co-primary outcomes were sensitivity compared to conventional microbiology and, for the prospective study, time to result. Metagenomic sequencing was performed to validate findings in prospective samples. Antibiotic free days (AFD) were compared between the study cohort and comparator group. 128 stored samples were tested, with sensitivity of 97% (95% confidence interval (CI) 88-100%). Prospectively, 95 patients were tested by TAC, with 71 forming the comparator group. TAC returned results 51 hours (interquartile range 41-69 hours) faster than culture and with sensitivity of 92% (95% CI 83-98%) compared to conventional microbiology. 94% of organisms identified by sequencing were detected by TAC. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). TAC group were more likely to experience antimicrobial de-escalation (odds ratio 2.9 (95%1.5-5.5)). Implementation of a syndromic molecular diagnostic approach to pneumonia led to faster results, with high sensitivity and impact on antibiotic prescribing.
肺炎的诊断一直受到依赖细菌培养的阻碍，细菌培养需要数天才能得出结果，而且结果常常为阴性。在重症患者中，这导致使用经验性广谱抗菌药物，不利于良好的抗菌药物管理。本研究的目的是建立一种综合征分子诊断方法的性能，使用一种涵盖52种呼吸道病原体的定制TaqMan阵列卡（TAC），并评估其对抗菌药物处方的影响。TAC针对支气管肺泡灌洗样本的回顾性多中心队列进行了验证。对疑似肺炎患者进行前瞻性评估时使用了TAC，同时设立了一个对照队列，该队列由TAC实验室团队无法提供服务时接受检查的患者组成。共同主要结局是与传统微生物学相比的敏感性，对于前瞻性研究而言，还有得出结果的时间。进行宏基因组测序以验证前瞻性样本中的发现。比较了研究队列和对照组之间的无抗生素天数（AFD）。对128份储存样本进行了检测，敏感性为97%（95%置信区间（CI）88 - 100%）。前瞻性地，95名患者接受了TAC检测，其中71名组成了对照队列。TAC得出结果的时间比培养快51小时（四分位间距41 - 69小时），与传统微生物学相比敏感性为92%（95%CI 83 - 98%）。测序鉴定出的生物体中有94%可被TAC检测到。TAC组的AFD分布存在显著差异，TAC组的AFD更多（p = 0.02）。TAC组更有可能经历抗菌药物降阶梯治疗（优势比2.9（95% 1.5 - 5.5））。采用综合征分子诊断方法诊断肺炎可更快得出结果，具有高敏感性并对抗生素处方产生影响。
