Plasma Microbial Cell-free DNA Next-generation Sequencing in the Diagnosis and Management of Febrile Neutropenia.
Clin Infect Dis
; 74(9): 1659-1668, 2022 05 03.
Article
em En
| MEDLINE
| ID: mdl-33870413
ABSTRACT
BACKGROUND:
Standard testing fails to identify a pathogen in most patients with febrile neutropenia (FN). We evaluated the ability of the Karius microbial cell-free DNA sequencing test (KT) to identify infectious etiologies of FN and its impact on antimicrobial management.METHODS:
This prospective study (ClinicalTrials.gov; NCT02912117) enrolled and analyzed 55 patients with FN. Up to 5 blood samples were collected per subject within 24 hours of fever onset (T1) and every 2 to 3 days. KT results were compared with blood culture (BC) and standard microbiological testing (SMT) results.RESULTS:
Positive agreement was defined as KT identification of ≥1 isolate also detected by BC. At T1, positive and negative agreement were 90% (9/10) and 31% (14/45), respectively; 61% of KT detections were polymicrobial. Clinical adjudication by 3 independent infectious diseases specialists categorized Karius results as unlikely to cause FN (N = 0); definite (N = 12) KT identified ≥1 organism also found by SMT within 7 days; probable (N = 19) KT result was compatible with a clinical diagnosis; possible (N = 10) KT result was consistent with infection but not considered a common cause of FN. Definite, probable, and possible cases were deemed true positives. Following adjudication, KT sensitivity and specificity were 85% (41/48) and 100% (14/14), respectively. Calculated time to diagnosis was generally shorter with KT (87%). Adjudicators determined real-time KT results could have allowed early optimization of antimicrobials in 47% of patients, by addition of antibacterials (20%) (mostly against anaerobes [12.7%]), antivirals (14.5%), and/or antifungals (3.6%); and antimicrobial narrowing in 27.3% of cases. CLINICAL TRIALS REGISTRATION NCT02912117.CONCLUSION:
KT shows promise in the diagnosis and treatment optimization of FN.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neutropenia Febril
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Ácidos Nucleicos Livres
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Observational_studies
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Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Clin Infect Dis
Ano de publicação:
2022
Tipo de documento:
Article