Abstract
Objectives: To evaluate the performance of metagenomic next generation sequencing (mNGS) using adequate criteria for the detection of pathogens in lower respiratory tract (LRT) samples with a paired comparison to conventional microbiology tests (CMT).Methods: One hundred sixty-seven patients were reviewed from four different intensive care units (ICUs) in mainland China during 2018 with both mNGS and CMT results of LRT samples available. The reads per million ratio (RPMsample/RPMnon−template−control ratio) and standardized strictly mapped reads number (SDSMRN) were the two criteria chosen for identifying positive pathogens reported from mNGS. A McNemar test was used for a paired comparison analysis between mNGS and CMT.Results: One hundred forty-nine cases were counted into the final analysis. The RPMsample/RPMNTC ratio criterion performed better with a higher accuracy for bacteria, fungi, and virus than SDSMRN criterion [bacteria (RPMsample/RPMNTC ratio vs. SDSMRN), 65.1 vs. 55.7%; fungi, 75.8 vs. 71.1%; DNA virus, 86.3 vs. 74.5%; RNA virus, 90.9 vs. 81.8%]. The mNGS was also superior in bacteria detection only if an SDSMRN ≥3 was used as a positive criterion with a paired comparison to culture [SDSMRN positive, 92/149 (61.7%); culture positive, 54/149 (36.2%); p < 0.001]; however, it was outperformed with significantly more fungi and DNA virus identification when choosing both criteria for positive outliers [fungi (RPMsample/RPMNTC ratio vs. SDSMRN vs. culture), 23.5 vs. 29.5 vs. 8.7%, p < 0.001; DNA virus (RPMsample/RPMNTC ratio vs. SDSMRN vs. PCR), 14.1 vs. 20.8 vs. 11.8%, p < 0.05].Conclusions: Metagenomic next generation sequencing may contribute to revealing the LRT infection etiology in hospitalized groups of potential fungal infections and in situations with less access to the multiplex PCR of LRT samples from the laboratory by choosing a wise criterion like the RPMsample/RPMNTC ratio.
Highlights
Lower respiratory tract (LRT) infection is a common cause of intensive care unit (ICU) admission
One hundred forty-nine cases were enrolled into the final analysis since the total sequencing reads in the mNGS reports of 18 patients were missing, making both Reads per million (RPM) and SDSMRN infeasible to calculate
The accuracy of the SDSMRN criterion in identifying Aspergillus spp. was the same as that of the RPM ratio criterion (89.3%, 95% CI 84.3–94.2%), but the SDSMRN criterion had a higher sensitivity (36.4%, 95% CI 12.4–68.4%) if comparing mNGS with culture (Figure 3, Table 3)
Summary
Lower respiratory tract (LRT) infection is a common cause of intensive care unit (ICU) admission. The Management of Severe sepsis in Asia’s Intensive Care unitS (MOSAICS) study revealed that among 1,285 severe sepsis patients admitted to Asian ICUs, 37.4% of the sources of infection were attributed to the lungs [1]. A point prevalence study of ICU infection, which recruited 1,150 centers, reported that less than two-thirds (5,259/8,135, 65%) of the ICU patients with probable or definite infections received at least one positive culture [3]. Even combining cultures, targeted molecular methods and serology all together to routinely investigate lower respiratory tract (LRT) infection microbial etiology, Leven et al found out that the potential pathogen detection rate was only 59% (1,844/3,104) in this study [4]. 40% of the cases were causative agents undetermined by conventional microbiological tests (CMT)
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