Plasma Metagenomic Next-Generation Sequencing Assay for Identifying Pathogens: a Retrospective Review of Test Utilization in a Large Children's Hospital.

Plasma metagenomic next-generation sequencing (mNGS) is a new diagnostic method used to potentially identify multiple pathogens with a single DNA-based diagnostic test. The test is expensive, and little is understood about where it fits into the diagnostic schema. We describe our experience at Texas Children's Hospital with the mNGS assay by Karius from Redwood City, CA, to determine whether mNGS offers additional diagnostic value when performed within 1 week before or after conventional testing (CT) (i.e., concurrently). We performed a retrospective review of all patients who had mNGS testing from April to June of 2019. Results for mNGS testing, collection time, time of result entry into the electronic medical record, and turnaround time were compared to those for CT performed concurrently. Discordant results were further reviewed for changes in antimicrobials due to the additional organism(s) identified by mNGS. Sixty patients had mNGS testing; the majority were immunosuppressed (62%). There was 61% positive agreement and 58% negative agreement between mNGS and CT. The mean time of result entry into the electronic medical record for CT was 3.5 days earlier than the mean result time for mNGS. When an additional organism(s) was identified by mNGS, antimicrobials were changed 26% of the time. On average, CT provided the same result as mNGS, but sooner than mNGS. When additional organisms were identified by mNGS, there was no change in management in the majority of cases. Overall, mNGS added little diagnostic value when ordered concurrently with CT.

Enteric Fever in Children: An Epidemiological and Clinical Review of Cases in Southeast Texas.

Extensively drug-resistant (XDR) strains of Salmonella enterica serotype Typhi have emerged in Pakistan and Iraq. We report 13 children with enteric fever in Southeast Texas seen over 3.5 years, of whom 23.1% had XDR isolates.

Plasma cell-free metagenomic next generation sequencing in the clinical setting for the diagnosis of infectious diseases: a systematic review and meta-analysis.

Plasma cell-free metagenomic next-generation sequencing (cf-mNGS) is a non-invasive method that may be able to identify thousands of pathogens through a hypothesis-free approach. There is a lack of consensus on how this test compares to conventional microbiologic testing. We conducted a systematic review and meta-analysis of published studies evaluating the accuracy of plasma cf-mNGS in hospitalized patients and present pooled estimates of the positive (PPA) and negative percent agreement (NPA) compared to a composite reference standard that included all conventional microbiological testing and clinical history as assessed by an adjudication panel or clinical treatment team. Five retrospective studies (n = 552) were included. The majority of the patients (56%-88%) were immunocompromised. The pooled PPA was 67% (95% CI, 54%-81%) and the pooled NPA was 70% (95% CI, 63%-77%). The pooled diagnostic performance characteristics suggest that cf-mNGS provides limited evidence for ruling in or out the presence of infection as commonly used.

Clinical Impact of Plasma Metagenomic Next-generation Sequencing in a Large Pediatric Cohort.

BACKGROUND: Plasma metagenomic next-generation sequencing (mNGS) has the potential to detect thousands of different organisms with a single test. There are limited data on the real-world impact of mNGS and even less guidance on the types of patients and clinical scenarios in which mNGS testing is beneficial. METHODS: A retrospective review of patients who had mNGS testing as part of routine clinical care at Texas Children's Hospital from June 2018-August 2019 was performed. Medical records were reviewed for pertinent data. An expert panel of infectious disease physicians adjudicated each unique organism identified by mNGS for clinical impact. RESULTS: There were 169 patients with at least one mNGS test. mNGS identified a definitive, probable or possible infection in 49.7% of patients. mNGS led to no clinical impact in 139 patients (82.2%), a positive impact in 21 patients (12.4%), and a negative impact in 9 patients (5.3%). mNGS identified a plausible cause for infection more often in immunocompromised patients than in immunocompetent patients (55.8% vs. 30.0%, P = 0.006). Positive clinical impact was highest in patients with multiple indications for testing (37.5%, P = 0.006) with deep-seated infections, overall, being most often associated with a positive impact. CONCLUSION: mNGS testing has a limited real-world clinical impact when ordered indiscriminately. Immunocompromised patients with well-defined deep-seated infections are likely to benefit most from testing. Further studies are needed to evaluate the full spectrum of clinical scenarios for which mNGS testing is impactful.