Plasma metagenomic next-generation sequencing of microbial cell-free DNA detects pathogens in patients with suspected infected pancreatic necrosis

Abstract Background: Infected pancreatic necrosis (IPN) is a life-threatening complication of acute pancreatitis (AP). Timely diagnosis of IPN could facilitate appropriate treatment, but there is a lack of reliable non-invasive screening tests. In this study, we aimed to evaluate the diagnostic value of plasma metagenomic next-generation sequencing (mNGS) based on circulating microbial cell-free DNA in patients with suspected IPN. Methods: From October 2020 to October 2021, 44 suspected IPN patients who underwent plasma mNGS were reviewed. Confirmatory diagnosis of IPN within two weeks after the index blood sampling was considered the reference standard. The confirmation of IPN relied on the microbiological results of drains obtained from the necrotic collections. The distribution of the pathogens identified by plasma mNGS was analyzed. Positive percent agreement (PPA) and negative percent agreement (NPA) were evaluated based on the conformity between the overall mNGS results and culture results of IPN drains. In addition, the clinical outcomes were compared between mNGS positive and negative patients. Results: Across all the study samples, thirteen species of bacteria and five species of fungi were detected by mNGS. The positivity rate of plasma mNGS was 54.55% (24/44). Of the 24 mNGS positive cases, twenty (83.33%, 95%CI, 68.42-98.24%) were consistent with the culture results of IPN drains. The PPA and NPA of plasma mNGS for IPN were 80.0% (20 /25; 95% CI, 64.32 – 95.68%) and 89.47% (17/19; 95% CI, 75.67 – 100%), respectively. Compared with the mNGS negative group, patients in the positive group had more new-onset septic shock (12 (50.0%) vs. 4 (20.0%), p=0.039). Conclusion: IPN relevant pathogens can be identified by plasma mNGS, potentially facilitating appropriate treatment. The clinical application of mNGS in this cohort appears feasible.