Diagnostic Value And Clinical Application Of Metagenomic Next-generation Sequencing For Infections In Critically Ill Patients

Objectives:To evaluate the diagnostic value and clinical application of metagenomic nextgeneration sequencing(mNGS)for infections in critically ill patients and mNGS-guided anti-infective treatment adjustment.Methods:We retrospectively reviewed 358 critically ill patients suspected of infection at the Provincial Hospital Affiliated to Anhui Medical University ICU,between April 2020 to September 2021.The following inclusion criteria were used:(1)CMT and mNGS tests were conducted at an interval of less than 24 hours and the specimens used for mNGS and CMT were of the same type;(2)the specimen collection of patients with communityacquired infection was completed less than 48 hours after ICU admission;(3)for patients with a hospital-acquired infection,specimens were collected less than 48 hours after the diagnosis ofinfection was determined.The exclusion criteria for patients were as follows:(1)cases retrospectively diagnosed as non-infectious diseases;(2)incomplete medical record;(3)specimen failing to pass quality control of mNGS;and(4)specimen leakage or pollution.The diagnostic performance of mNGS was evaluated by using the conventional microbiological tests(CMT)method as the reference standard,and subgroup analysis was performed by different sample types.According to the immune status,the patients were divided into immunocompetent and immunocompromised group;The patients were divided into community-acquired infection(CAI)and hospital-acquired infection(HAI)groups according to the location of infection.The difference of pathogenic spectrum between groups was compared,and the effect of mNGS-guided anti-infective treatment adjustment scheme was analyzed in critically ill patients.Results:Finally,234 patients were enrolled.In general,the sensitivity and specificity of mNGS for bacterial and fungal detection were 94.3%(95%confidence interval[CI],89.3%-99.2%)and 50.3%(95%CI,42.2%-58.5%),and 85.7%(95%CI,64.8%-106.7%)and 88.2%(95%CI,83.9%-92.5%),respectively.152 viruses were detected by mNGS,but only 28 viruses were considered causative agents.Pneumocystis jirovecii and Human cytomegalovirus were more common in the immunocompromised group.The proportion of mNGS-guided beneficial anti-infective therapy adjustments in the immunocompromised group was greater than in the immunocompetent group(48.5%vs.30.1%;P=0.008).Bacterial infections in the HAI group was higher than that in CAI group(82%vs 56%;p<0.001).However,there was no statistical difference in the effect of mNGS-guided anti-infective therapy adjustment between the groups.In addition,peripheral blood and BALF specimens had the highest proportion of beneficial adjustments to mNGS-guided anti-infective treatment adjustment(39.0%;40.0%),but peripheral blood mNGS-guided anti-infective treatment adjustment were also unhelpful in 22.0%of patientsConclusions:In summary,mNGS has significant advantages for the detection of both common and uncommon pathogen compared with CMT.mNGS is expected to be a promising technology that provides precision medicine for critically ill patients with infection,especially in those who are immunocompromised.