Metagenomic Next-Generation Sequencing, instead of Procalcitonin, Could Guide Antibiotic Usage in Patients with Febrile Acute Necrotizing Pancreatitis: A Multicenter, Prospective Cohort Study

Metagenomic Next-Generation Sequencing as an Alternative to Procalcitonin in Guiding Antibiotic Use in Patients with Acute Necrotizing Pancreatitis and Fever

Background and Research Objectives

Acute pancreatitis (AP) is one of the leading causes of emergency hospital admissions for digestive system diseases, with significant medical resource utilization. The disease is accompanied by local and systemic inflammatory responses, and the clinical course varies. Approximately 20% of patients develop acute necrotizing pancreatitis (ANP), and 20-40% of these cases progress to infected pancreatic necrosis (IPN), with a mortality rate of 30-40%. Since sterile ANP and IPN present similarly in clinical manifestations, physicians face significant challenges in early diagnosis of IPN, leading to antibiotic overuse. This not only contributes to antimicrobial resistance but also increases unnecessary adverse drug reactions and higher medical costs. Therefore, a simple and effective method for diagnosing pancreatic infection and guiding rational antibiotic use is needed.

Previously, procalcitonin (PCT) was highly anticipated as a sensitive biomarker for bacterial infection. However, the use of PCT-guided antibiotics in acute pancreatitis (AP) patients remains controversial, especially in moderately severe or febrile ANP patients, where no significant difference in the risk of antibiotic use was observed.

Metagenomic next-generation sequencing (mNGS) is a culture-independent analysis method that uses sequencing technology to study a mixture of microbial genomes, theoretically allowing for the detection of all pathogens in clinical samples through a single sequencing run. Through technology developed by BGI China, mNGS has been successfully applied in the diagnosis of infections in blood, urine, feces, cerebrospinal fluid, respiratory secretions, and tissues. mNGS is particularly suitable for diagnosing rare, complex, or novel pathogen infections, and it is cost-effective and has a relatively short turnaround time, making it highly promising for clinical applications.

Research Source

This research paper was written by a team of medical doctors, including Chiayen Lin, Jiarong Li, Baiqi Liu, Xiaoyue Hong, and others, affiliated with institutions such as Xiangya Hospital of Central South University, Changde Hospital, and the First People’s Hospital of Hunan Province. This study was published in the International Journal of Surgery on February 9, 2024.

Research Design and Methods

This study was a prospective, multicenter, observational clinical trial conducted from May 2023 to October 2023, aimed at evaluating the effectiveness of blood mNGS compared to procalcitonin and blood culture in diagnosing infected pancreatic necrosis and guiding antibiotic use.

Research Process

  1. Subject Selection: Febrile ANP patients were selected, defined as having a body temperature ≥38.5°C at least once during the disease process, with clinical manifestations of sepsis in the absence of abdominal or retroperitoneal invasive procedures. Blood samples were collected for mNGS, procalcitonin, and blood culture analyses.

  2. Sample Processing: Collected blood samples served as the basis for testing, and other routine biochemical markers, such as C-reactive protein, were also collected. For patients meeting surgical indications, peripancreatic tissue samples were also collected during the initial surgical intervention for microbial culture.

  3. Experimental Analysis: mNGS and bioinformatics analysis were provided by BGI China. Procalcitonin and microbial culture analyses were performed by the respective research centers according to standard protocols, with a positive procalcitonin threshold set at 1.0 ng/ml.

  4. Data Collection: Clinical presentations, laboratory test results, imaging findings, antibiotic use, and clinical outcomes were collected based on electronic medical records.

  5. Treatment Regimen: Febrile ANP patients were treated with broad-spectrum antibiotics when their body temperature exceeded 38.5°C. If antibiotic treatment failed, stepwise surgical interventions were employed.

Research Results

From May 2023 to October 2023, a total of 78 febrile ANP patients were included in the study. Of these, 30 cases were diagnosed with infected pancreatic necrosis (IPN), and 48 cases were sterile pancreatic necrosis (SPN). Compared to procalcitonin and blood culture, mNGS demonstrated higher sensitivity (86.7% vs. 56.7% vs. 26.7%, p < 0.001) and higher negative predictive value (89.5 vs. 61.4%, p < 0.01) in diagnosing IPN. The overall diagnostic accuracy of mNGS was also significantly better than the other two methods (85.7% vs. 65.7% vs. 61.4%).

Furthermore, multivariate analysis showed that a positive mNGS result (OR=60.2, p < 0.001) and lower fibrinogen levels (OR=2.0, p < 0.05) were independent predictors of IPN. In contrast, procalcitonin was only associated with increased mortality (OR=11.7, p = 0.006).

Research Conclusions and Clinical Implications

This study demonstrated that blood mNGS has significant value in the early diagnosis of IPN and guiding antibiotic use in febrile ANP patients. mNGS not only significantly improved diagnostic accuracy but also reduced unnecessary antibiotic use, thereby avoiding antimicrobial resistance and lowering medical costs. Compared to traditional methods, mNGS more precisely identified pathogens, greatly aiding in the rational selection and use of antibiotics.

Research Highlights

  • Superior Diagnostic Performance: mNGS significantly outperformed procalcitonin and blood culture, demonstrating higher sensitivity and negative predictive value.
  • Guidance for Antibiotic Use: mNGS reduced inappropriate antibiotic use and increased the proportion of correct antibiotic use.
  • Independent Predictive Factor: mNGS results were an important independent predictor of IPN, guiding clinical decision-making.
  • Multicenter Validation: The study included seven hospitals in China, providing strong representation and broad applicability.

Other Notable Information

Nevertheless, the study had certain limitations, such as the inherent limitations of observational studies and the possibility of misclassifying IPN cases that received antimicrobial treatment but did not undergo intervention as SPN. Future larger-scale randomized controlled trials are needed to further validate the clinical application of mNGS.

This study emphasized the potential of mNGS in the early diagnosis of pancreatic infection and guidance of antibiotic use, providing new insights for optimizing treatment strategies for acute necrotizing pancreatitis.