Abstract
BACKGROUND Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test. METHODS In a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review. RESULTS We enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment. CONCLUSIONS Routine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2327-2340 |
| Number of pages | 14 |
| Journal | New England Journal of Medicine |
| Volume | 380 |
| Issue number | 24 |
| DOIs | |
| State | Published - Jun 13 2019 |
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ASJC Scopus subject areas
- Medicine(all)
Cite this
Clinical metagenomic sequencing for diagnosis of meningitis and encephalitis. / Wilson, M. R.; Sample, H. A.; Zorn, K. C.; Arevalo, S.; Yu, G.; Neuhaus, J.; Federman, S.; Stryke, D.; Briggs, B.; Langelier, C.; Berger, A.; Douglas, V.; Josephson, S. A.; Chow, F. C.; Fulton, B. D.; DeRisi, J. L.; Gelfand, J. M.; Naccache, S. N.; Bender, J.; Dien Bard, J.; Murkey, J.; Carlson, M.; Vespa, P. M.; Vijayan, T.; Allyn, P. R.; Campeau, S.; Humphries, R. M.; Klausner, J. D.; Ganzon, C. D.; Memar, F.; Ocampo, N. A.; Zimmermann, Lara; Cohen, Stuart H; Polage, Christopher R; DeBiasi, R. L.; Haller, B.; Dallas, R.; Maron, G.; Hayden, R.; Messacar, K.; Dominguez, S. R.; Miller, S.; Chiu, C. Y.
In: New England Journal of Medicine, Vol. 380, No. 24, 13.06.2019, p. 2327-2340.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Clinical metagenomic sequencing for diagnosis of meningitis and encephalitis
AU - Wilson, M. R.
AU - Sample, H. A.
AU - Zorn, K. C.
AU - Arevalo, S.
AU - Yu, G.
AU - Neuhaus, J.
AU - Federman, S.
AU - Stryke, D.
AU - Briggs, B.
AU - Langelier, C.
AU - Berger, A.
AU - Douglas, V.
AU - Josephson, S. A.
AU - Chow, F. C.
AU - Fulton, B. D.
AU - DeRisi, J. L.
AU - Gelfand, J. M.
AU - Naccache, S. N.
AU - Bender, J.
AU - Dien Bard, J.
AU - Murkey, J.
AU - Carlson, M.
AU - Vespa, P. M.
AU - Vijayan, T.
AU - Allyn, P. R.
AU - Campeau, S.
AU - Humphries, R. M.
AU - Klausner, J. D.
AU - Ganzon, C. D.
AU - Memar, F.
AU - Ocampo, N. A.
AU - Zimmermann, Lara
AU - Cohen, Stuart H
AU - Polage, Christopher R
AU - DeBiasi, R. L.
AU - Haller, B.
AU - Dallas, R.
AU - Maron, G.
AU - Hayden, R.
AU - Messacar, K.
AU - Dominguez, S. R.
AU - Miller, S.
AU - Chiu, C. Y.
PY - 2019/6/13
Y1 - 2019/6/13
N2 - BACKGROUND Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test. METHODS In a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review. RESULTS We enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment. CONCLUSIONS Routine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases.
AB - BACKGROUND Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test. METHODS In a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review. RESULTS We enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment. CONCLUSIONS Routine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases.
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U2 - 10.1056/NEJMoa1803396
DO - 10.1056/NEJMoa1803396
M3 - Article
VL - 380
SP - 2327
EP - 2340
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 24
ER -