Negative results of bronchoalveolar lavage fluid metagenomic next-generation sequencing in critically ill patients

Abstract

ObjectiveReports on negative results of metagenomic next-generation sequencing (mNGS) are scarce. We aimed to explore the diagnostic value of negative results in bronchoalveolar lavage fluid (BALF) mNGS and how to deal with the negative results in patients with severe respiratory disease.MethodsA retrospective analysis was performed on patients suspected severe community-acquired pneumonia who were admitted to the respiratory intensive care unit of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021. According to the final diagnosis as the reference standard, the negative results of mNGS were divided into a true negative group and a false negative group. For enrolled patients, we recorded their demographic data, imaging results, laboratory results, therapeutic processes, and prognoses.ResultsA total of 21 patients were enrolled in this study, including 16 true negative patients and 5 false negative patients. In the true negative group, interstitial lung diseases were the most and neoplastic diseases were following. In addition to mNGS, 9 patients underwent pathological examination, 7 patients were finally diagnosed by medical history, autoantibodies, and point-of-care (POC) ultrasound. 14 patients eventually discontinued antibiotics, 2 patients underwent antibiotic de-escalation, the average interval time of treatment adjustment was 3.56 ± 2.00 days. In the false negative group, the leading missed pathogen was fungi, followed by tuberculosis bacilli. In contrast to 2 patients underwent pathological examination, 3 patients were confirmed by routine microbiological tests.ConclusionsNegative results of BALF mNGS can help to rule out infection, but missed diagnoses may also exist. It should be re-evaluated with other clinical informations. Pathological examination or repeated mNGS may be viable options when the diagnosis cannot be confirmed.

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“…In addition, considering the serious condition, we continued the empiric treatment for patients with negative results of mNGS. Despite the high sensitivity, negative results of mNGS can help to rule out pulmonary infection, but missed diagnoses may also exist [ 27 ]. In the face of negative results of mNGS, antibiotic de-escalation or discontinuation should be cautious, unless routine microbiological tests were also negative and patients were clinically improving without signs of active infection.…”

Combination of transbronchial cryobiopsy based clinic-radiologic-pathologic strategy and metagenomic next-generation sequencing for differential diagnosis of rapidly progressive diffuse parenchymal lung diseases

“…Ma et al. explored the clinical significance of negative results of BALF mNGS, demonstrated that negative results of mNGS can help to exclude infection ( Ma et al., 2022 ). Qian et al.…”

“…Exclusion of infection remains important. Ma et al explored the clinical significance of negative results of BALF mNGS, demonstrated that negative results of mNGS can help to exclude infection (Ma et al, 2022). Qian et al evaluated the clinical value of negative mNGS results and found that when the mNGS test is negative, the negative prediction accuracy rate of the original specimen is significant (Qian et al, 2022).…”

Respiratory metagenomics: route to routine service

“…The content and time of report production needs consideration. Accurate organism identification is possible from sequencing <0.1% of the genome after a few minutes so there may be benefit producing organism profile or ''No (significant) organisms detected'' reports first [45]. Alternatively, clinicians may prefer waiting for a single report a few hours later that includes presence of specific resistance or virulence genes and predictions for phenotypic susceptibilities.…”