Clinical Characteristics and the Effect of Timing for Metagenomic Next-Generation Sequencing in Critically Ill Patients with Sepsis

Abstract

Background

Metagenomic next-generation sequencing (mNGS) has a good performance for the identification of pathogens in infectious diseases, but few studies on the clinical characteristics of mNGS and the effect of timing for mNGS in critically ill patients with sepsis.

Methods

We retrospectively included all patients diagnosed with sepsis after admission to the intensive care unit (ICU) of a university-affiliated hospital between Aug 1, 2019 and Apr 1, 2021. During the study period, pathogens for all enrolled subjects were obtained by mNGS. We analyzed the composition and positive rate of different samples type for mNGS. And then we used the univariable and multivariable logistic regression to explore the risk factors associated with all-cause mortality at 28 days.

Results

A total of 87 patients were included and 87 samples were analyzed among these patients. The most common sample for mNGS was bronchoalveolar lavage fluid (BALF), about 84% (73/87). The positive rate of pathogens identification by mNGS was higher than conventional culture (92% vs 36%, p < 0.001). In addition to the pathogens detected by conventional culture, mNGS can detect more viruses and fungi. Based on the mNGS report, clinicians made adjustments to the antibiotic regimen for 72% patients. The multivariate binary logistic regression analysis suggested that age (OR, 1.036; 95% CI, 1.005–1.067; p = 0.021) and the sequential organ failure assessment (SOFA) score on the day of mNGS sampling were independent risk factors of death at 28 days (OR, 1.204; 95% CI, 1.038–1.397; p = 0.014).

Conclusion

In critically ill patients with sepsis, the most common sample type for mNGS was BALF, and the positive rate of mNGS is higher than conventional cultures, especially in viruses and fungi. Meanwhile, mNGS can guide clinicians in adjusting antibiotic regimens. Age and the SOFA score on the day of mNGS sampling were independent risk factors for death.

Keywords:

• sepsis
• metagenomic next-generation sequencing
• critical care
• timing
• outcome

Abbreviations

mNGS, metagenomic next-generation sequencing; ICU, intensive care unit; BALF, bronchoalveolar lavage fluid; SOFA, sequential organ failure assessment; PCR, polymerase chain reaction; CSF, cerebrospinal fluid; P/F, The ratio of arterial oxygen partial pressure to fractional inspired oxygen; DNB, DNA nanoball; SMRN, stringent map read number; IQR, interquartile range; CI, confidence intervals; ROC, Receiver Operating Characteristic; ROC-AUC, the area under the ROC curve.

Ethics Approval and Informed Consent

The study was conducted in accordance with the Declaration of Helsinki. The study was approved by the ethics committee of the Affiliated Hospital of Guizhou Medical University (2020115K). The registration number of the clinical study is ChiCTR2100043089. Informed consent was waived because this was a retrospective study. We obtained patient data from the Medical Records and analysed the data anonymously.

Acknowledgments

We thank all the participants in this study.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest.

Additional information

Funding

This study was supported by the funds from the National key research and development plan (2018YFC2001904), the National Science Foundation of China (Grant Nos. 81701958 and 81960357), Guizhou Provincial Science and Technology Projects (Qian Ke He Jichu[2020]1Y330, Qian Ke He Jichu-ZK[2022]Yiban 370), National Key Clinical Specialty Construction Project of China (2011-170), Key Clinical Discipline Construction Project of Guizhou Province (2011-52) and Special Aid Fund for High-level Personnel in Guizhou Province (TZJF-2011-25).