Dierikx Thomas H, Visser Douwe H, de Meij Tim, Versalovic James, Leeflang Mariska Mg, Cooper Chris, Pammi Mohan
Department of Medical Microbiology, Infectious Diseases & Infection Prevention, Maastricht University Medical Center, Maastricht, Netherlands.
Department of Pediatric Gastroenterology, Amsterdam UMC, Amsterdam, Netherlands.
Cochrane Database Syst Rev. 2025 Mar 19;3(3):CD011926. doi: 10.1002/14651858.CD011926.pub3.
Microbial cultures for diagnosis of neonatal sepsis have low sensitivity and reporting delay. Advances in molecular microbiology have fostered new molecular assays that are rapid and may improve neonatal outcomes.
To assess the diagnostic accuracy of various molecular methods for the diagnosis of culture-positive bacterial and fungal sepsis in neonates and to explore heterogeneity among studies by analyzing subgroups classified by gestational age and type of sepsis onset and compare molecular tests with one another.
We searched CENTRAL, MEDLINE, Embase and trial registries in August 2023. We checked reference lists of included studies and systematic reviews where subject matter related to the intervention or population examined in this review.
We included studies that were prospective or retrospective, cohort or cross-sectional design, which evaluated molecular assays (index test) in neonates with suspected sepsis in comparison with microbial cultures (reference standard).
Two review authors independently screened studies, extracted data and assessed the methodological quality of the studies. We performed meta-analyses using the bivariate model and entered data into Review Manager.
Seventy-four studies were eligible for inclusion, of which 68 studies provided data for meta-analysis. The total number of participants was 14,309 (1328 infants who were culture-positive and 12,981 infants who were culture-negative) from 68 studies that were included in the meta-analysis. The summary estimate of sensitivity was 0.91 (95% confidence interval (CI) 0.85 to 0.95) and of specificity was 0.88 (95% CI 0.83 to 0.92) (low-certainty evidence). We explored heterogeneity by subgroup analyses of type of test, gestational age, type of sepsis onset and prevalence of sepsis. We found insufficient explanations for the heterogeneity (low- to very low-certainty evidence). Sensitivity analyses including studies that analyzed blood samples, using good methodology and those that did not use multiple samples from the same participant revealed similar results (low-certainty evidence).
AUTHORS' CONCLUSIONS: Molecular assays have the advantage of producing rapid results and have moderate diagnostic accuracy. Molecular assays may prevent overuse of antibiotics in neonates with suspected sepsis. The efficacy and cost-effectiveness of these molecular assays should be evaluated using randomized trials comparing molecular assays as an add-on test versus conventional methods without the add-on test in neonates with suspected sepsis.
用于诊断新生儿败血症的微生物培养敏感性低且报告延迟。分子微生物学的进展催生了新的分子检测方法，这些方法快速且可能改善新生儿预后。
评估各种分子方法诊断新生儿培养阳性细菌和真菌败血症的诊断准确性，并通过分析按胎龄和败血症发病类型分类的亚组来探索研究之间的异质性，以及相互比较分子检测方法。
我们于2023年8月检索了Cochrane系统评价数据库、MEDLINE、Embase和试验注册库。我们检查了纳入研究和系统评价的参考文献列表，这些文献的主题与本评价中所研究的干预措施或人群相关。
我们纳入了前瞻性或回顾性、队列或横断面设计的研究，这些研究评估了疑似败血症新生儿的分子检测方法（索引检测）并与微生物培养（参考标准）进行比较。
两位综述作者独立筛选研究、提取数据并评估研究的方法学质量。我们使用双变量模型进行荟萃分析，并将数据录入Review Manager软件。
74项研究符合纳入标准，其中68项研究提供了荟萃分析数据。纳入荟萃分析的68项研究中，参与者总数为14309名（1328名培养阳性婴儿和12981名培养阴性婴儿）。敏感性的汇总估计值为0.91（95%置信区间（CI）0.85至0.95），特异性为0.88（95%CI 0.83至0.92）（低确定性证据）。我们通过对检测类型、胎龄、败血症发病类型和败血症患病率进行亚组分析来探索异质性。我们发现对异质性的解释不足（低至极低确定性证据）。敏感性分析包括分析血样的研究、采用良好方法的研究以及未使用同一参与者多个样本的研究，结果相似（低确定性证据）。
分子检测方法具有快速出结果的优势，且诊断准确性中等。分子检测方法可能会防止对疑似败血症新生儿过度使用抗生素。应使用随机试验评估这些分子检测方法的疗效和成本效益，该试验将分子检测方法作为附加检测与疑似败血症新生儿中不使用附加检测的传统方法进行比较。
