Potential of plasma metagenomic next-generation sequencing to guide antibiotic therapy in acute necrotizing pancreatitis with early fever: a prospective multicenter cohort study

Indiscriminate antibiotic use remains common in febrile patients with acute necrotizing pancreatitis (ANP), particularly during the early phase. Metagenomic next‑generation sequencing (mNGS) has shown diagnostic utility for infected pancreatic necrosis (IPN) and may offer a means to guide antimicrobial therapy. We aimed to explore whether mNGS could potentially improve the appropriateness of antibiotic use in ANP patients presenting with early fever. This prospective multicenter cohort study was conducted at five hospitals in China, enrolling ANP patients who developed fever within two weeks of symptom onset. Antibiotic susceptibility was defined per local microbiology laboratory reports. The hypothetical impact of mNGS on reducing inappropriate antibiotic use was evaluated through a retrospective simulation using predefined criteria from the BGI China antimicrobial drug usage card, as mNGS results were not disclosed to the treating teams during the actual clinical course. Between May 2023 and December 2024, 125 ANP patients with early fever were enrolled. Antibiotics were administered to 91.2% (114/125) of patients, whereas only 23.2% (29/125)were eventually confirmed to have IPN, and the rate of appropriate antibiotic use was 14.5% (17/117) based on conventional culture. In our simulated model, if therapy had been guided by plasma mNGS results, the estimated rate of appropriate antibiotic use could have increased to 71.8%. Plasma mNGS facilitates rapid pathogen identification and shows potential for improving antibiotic appropriateness in ANP patients with early fever.