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Abstract：
BACKGROUND: The effectiveness of procalcitonin-based algorithms in guiding antibiotic usage for febrile acute necrotizing pancreatitis (ANP) remains controversial. Metagenomic next-generation sequencing (mNGS) has been applied to diagnose infectious diseases. The authors aimed to evaluate the effectiveness of blood mNGS in guiding antibiotic stewardship for febrile ANP.
METHODS: The prospective multicenter clinical trial was conducted at seven hospitals in China. Blood samples were collected during fever (T ≥38.5°C) from ANP patients. The effectiveness of blood mNGS, procalcitonin, and blood culture in diagnosing pancreatic infection was evaluated and compared. Additionally, the real-world utilization of antibiotics and the potential mNGS-guided antimicrobial strategy in febrile ANP were also analyzed.
RESULTS: From May 2023 to October 2023, a total of 78 patients with febrile ANP were enrolled and 30 patients (38.5%) were confirmed infected pancreatic necrosis (IPN). Compared with procalcitonin and blood culture, mNGS showed a significantly higher sensitivity rate (86.7% vs. 56.7% vs. 26.7%, P <0.001). Moreover, mNGS outperformed procalcitonin (89.5 vs. 61.4%, P <0.01) and blood culture (89.5 vs. 69.0%, P <0.01) in terms of negative predictive value. Blood mNGS exhibited the highest accuracy (85.7%) in diagnosing IPN and sterile pancreatic necrosis, significantly superior to both procalcitonin (65.7%) and blood culture (61.4%). In the multivariate analysis, positive blood mNGS (OR=60.2, P <0.001) and lower fibrinogen level (OR=2.0, P <0.05) were identified as independent predictors associated with IPN, whereas procalcitonin was not associated with IPN, but with increased mortality (Odds ratio=11.7, P =0.006). Overall, the rate of correct use of antibiotics in the cohort was only 18.6% (13/70) and would be improved to 81.4% (57/70) if adjusted according to the mNGS results.
CONCLUSIONS: Blood mNGS represents important progress in the early diagnosis of IPN, with particular importance in guiding antibiotic usage for patients with febrile ANP.
METHODS: The prospective multicenter clinical trial was conducted at seven hospitals in China. Blood samples were collected during fever (T ≥38.5°C) from ANP patients. The effectiveness of blood mNGS, procalcitonin, and blood culture in diagnosing pancreatic infection was evaluated and compared. Additionally, the real-world utilization of antibiotics and the potential mNGS-guided antimicrobial strategy in febrile ANP were also analyzed.
RESULTS: From May 2023 to October 2023, a total of 78 patients with febrile ANP were enrolled and 30 patients (38.5%) were confirmed infected pancreatic necrosis (IPN). Compared with procalcitonin and blood culture, mNGS showed a significantly higher sensitivity rate (86.7% vs. 56.7% vs. 26.7%, P <0.001). Moreover, mNGS outperformed procalcitonin (89.5 vs. 61.4%, P <0.01) and blood culture (89.5 vs. 69.0%, P <0.01) in terms of negative predictive value. Blood mNGS exhibited the highest accuracy (85.7%) in diagnosing IPN and sterile pancreatic necrosis, significantly superior to both procalcitonin (65.7%) and blood culture (61.4%). In the multivariate analysis, positive blood mNGS (OR=60.2, P <0.001) and lower fibrinogen level (OR=2.0, P <0.05) were identified as independent predictors associated with IPN, whereas procalcitonin was not associated with IPN, but with increased mortality (Odds ratio=11.7, P =0.006). Overall, the rate of correct use of antibiotics in the cohort was only 18.6% (13/70) and would be improved to 81.4% (57/70) if adjusted according to the mNGS results.
CONCLUSIONS: Blood mNGS represents important progress in the early diagnosis of IPN, with particular importance in guiding antibiotic usage for patients with febrile ANP.
摘要：
背景：基于降钙素原的算法在指导发热性急性坏死性胰腺炎（ANP）抗生素使用方面的有效性仍存在争议。宏基因组下一代测序（mNGS）已用于诊断传染病。我们旨在评估血液mNGS在指导高热ANP抗生素管理中的有效性。
方法：前瞻性多中心临床试验在中国7家医院进行。在发烧期间（T≥38.5°C）从ANP患者收集血液样本。血液mNGS的有效性，降钙素原,评价和比较血培养对胰腺感染的诊断价值。此外,还分析了发热性ANP中抗生素的实际使用情况和mNGS指导的潜在抗菌策略。
结果：从2023年5月至2023年10月，共纳入78例发热性ANP患者，其中30例（38.5％）被确认为感染性胰腺坏死（IPN）。与降钙素原和血培养相比，mNGS显示出显着更高的敏感性（86.7%vs.56.7%vs.26.7%,P<0.001)。此外，mNGS的表现优于降钙素原（89.5%与61.4%,P<0.01）和血培养（89.5％vs.69.0%,P<0.01)在阴性预测值方面。血液mNGS在诊断IPN和无菌胰腺坏死（SPN）方面表现出最高的准确性（85.7％），显著优于降钙素原(65.7%)和血培养(61.4%)。在多变量分析中，血mNGS阳性（OR=60.2，P<0.001）和纤维蛋白原水平较低（OR=2.0，P<0.05）被确定为与IPN相关的独立预测因子，而降钙素原与IPN无关，但死亡率增加(OR=11.7,P=0.006)。总的来说,队列中抗生素的正确使用率仅为18.6%(13/70),如果根据mNGS结果进行调整,则会提高至81.4%(57/70).
结论：血mNGS是IPN早期诊断的重要进展，对指导发热性ANP患者使用抗生素特别重要。
方法：前瞻性多中心临床试验在中国7家医院进行。在发烧期间（T≥38.5°C）从ANP患者收集血液样本。血液mNGS的有效性，降钙素原,评价和比较血培养对胰腺感染的诊断价值。此外,还分析了发热性ANP中抗生素的实际使用情况和mNGS指导的潜在抗菌策略。
结果：从2023年5月至2023年10月，共纳入78例发热性ANP患者，其中30例（38.5％）被确认为感染性胰腺坏死（IPN）。与降钙素原和血培养相比，mNGS显示出显着更高的敏感性（86.7%vs.56.7%vs.26.7%,P<0.001)。此外，mNGS的表现优于降钙素原（89.5%与61.4%,P<0.01）和血培养（89.5％vs.69.0%,P<0.01)在阴性预测值方面。血液mNGS在诊断IPN和无菌胰腺坏死（SPN）方面表现出最高的准确性（85.7％），显著优于降钙素原(65.7%)和血培养(61.4%)。在多变量分析中，血mNGS阳性（OR=60.2，P<0.001）和纤维蛋白原水平较低（OR=2.0，P<0.05）被确定为与IPN相关的独立预测因子，而降钙素原与IPN无关，但死亡率增加(OR=11.7,P=0.006)。总的来说,队列中抗生素的正确使用率仅为18.6%(13/70),如果根据mNGS结果进行调整,则会提高至81.4%(57/70).
结论：血mNGS是IPN早期诊断的重要进展，对指导发热性ANP患者使用抗生素特别重要。
