Evidence map›Paper›PMID 33870413›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2022

Plasma Microbial Cell-free DNA Next-generation Sequencing in the Diagnosis and Management of Febrile Neutropenia.

Esther Benamu, Kiran Gajurel, Jill N Anderson, Tullia Lieb, Carlos A Gomez, Hon Seng, Romielle Aquino, Desiree Hollemon, David K Hong, Timothy A Blauwkamp and 8 more

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02912117 (Determining the Etiologic Diagnosis in Febrile Neutropenia Using the Karius Sequencing-based Infectious Disease Diagnostic Assay), which is not on this map. Cited by 66 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
12.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02912117 completednot on this map

Determining the Etiologic Diagnosis in Febrile Neutropenia Using the Karius Sequencing-based Infectious Disease Diagnostic Assay

TypeobservationalSponsorKarius, Inc.Ran2016 to 2018Enrolled57ConditionsInfection, Neutropenia
3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.

  1. Pooled it
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  9. Plasma Microbial Cell-free DNA Metagenomic Sequencing for Diagnosis of Invasive Fungal Diseases Among High-risk Outpatient and Inpatient Immunocompromised Hosts.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025
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  18. Mucormycosis.Infectious disease clinics of North America · 2025
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6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 8 institutions in 1 country.

Esther BenamuSchool of Medicine, Division of Infectious Diseases, University of Colorado Denver, Aurora, Colorado, USA.
Kiran GajurelDivision of Infectious Diseases, Carolinas Medical Center, Atrium Health, Charlotte, North Carolina, USA.ORCID 0000-0002-2185-1600
Jill N AndersonDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Tullia LiebHematopoietic Malignancies Unit Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA.
Carlos A GomezDivision of Infectious Diseases, Department of Medicine, University of Utah, Salt Lake City, Utah, USA.
Hon SengCytovale, Inc., San Francisco, California, USA.
Romielle AquinoKarius, Inc., Redwood City, California, USA.
Desiree HollemonKarius, Inc., Redwood City, California, USA.
David K HongVir Biotechnology Inc., San Francisco, California, USA.
Timothy A BlauwkampKarius, Inc., Redwood City, California, USA.
Mickey KerteszKarius, Inc., Redwood City, California, USA.
Lily BlairKarius, Inc., Redwood City, California, USA.
Paul L BollykyDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Bruno C MedeirosDivision of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Steven CoutreDivision of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Simona ZompiSangamo Therapeutics Inc, Brisbane, California, USA.
Jose G MontoyaThe Dr. Jack S. Remington Laboratory for Specialty Diagnostics at the Palo Alto Medical Foundation, Palo Alto, California, USA.
Stan DeresinskiDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Stanford University · USCarolinas Medical Center · USCytovale (United States) · USSangamo BioSciences (United States) · USUniversity of California, San Francisco · USUniversity of Colorado Denver · USUniversity of Utah · USVIR Biotechnology (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundStandard 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.

methodsThis 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.

resultsPositive 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.

conclusionKT shows promise in the diagnosis and treatment optimization of FN.

Indexed as

Cell-Free Nucleic AcidsFebrile NeutropeniaAnti-Bacterial AgentsFeverHigh-Throughput Nucleotide SequencingHumansProspective StudiesAnti-Bacterial AgentsCell-Free Nucleic AcidsFebrile neutropeniainfectionnext-generation sequencing

Identifiers

PMID33870413
PMCPMC9070798
OpenAlexW3156645577

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.