Dataset Information

Next-Generation Sequencing to Detect Pathogens in Pediatric Febrile Neutropenia: A Single-Center Retrospective Study of 112 Cases.

ABSTRACT:

Background

Febrile neutropenia (FN) is a frequent complication in immunocompromised patients. However, causative microorganisms are detected in only 10% of patients. This study aimed to detect the microorganisms that cause FN using next-generation sequencing (NGS) to identify the genome derived from pathogenic microorganisms in the bloodstream. Here, we implemented a metagenomic approach to comprehensively analyze microorganisms present in clinical samples from patients with FN.

Methods

FN is defined as a neutrophil count <500 cells/µL and fever ≥37.5°C. Plasma/serum samples of 112 pediatric patients with FN and 10 patients with neutropenia without fever (NE) were sequenced by NGS and analyzed by a metagenomic pipeline, PATHDET.

Results

The putative pathogens were detected by NGS in 5 of 10 FN patients with positive blood culture results, 15 of 87 FN patients (17%) with negative blood culture results, and 3 of 8 NE patients. Several bacteria that were common in the oral, skin, and gut flora were commonly detected in blood samples, suggesting translocation of the human microbiota to the bloodstream in the setting of neutropenia. The cluster analysis of the microbiota in blood samples using NGS demonstrated that the representative bacteria of each cluster were mostly consistent with the pathogens in each patient.

Conclusions

NGS technique has great potential for detecting causative pathogens in patients with FN. Cluster analysis, which extracts characteristic microorganisms from a complex microbial population, may be effective to detect pathogens in minute quantities of microbiota, such as those from the bloodstream.

SUBMITTER: Horiba K

PROVIDER: S-EPMC8634086 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAntipseudomonal β-lactams have been used for the treatment of febrile neutropenia (FN); however, the efficacy and safety of antipseudomonal β-lactams in pediatric patients remain unclear. The aim of this study was to comprehensively compare the efficacy and side effects of optional antipseudomonal β-lactams for pediatric FN.MethodsPubMed, Embase, Medline, and Cochrane Library were systematically searched from their inception to December 18, 2020. Eligible randomized controlled trials in which pediatric FN patients were treated with an empiric monotherapy of antipseudomonal β-lactams were selected. Data synthesis was performed using WinBUGS 14.0 software and meta packages implemented in R 3.6.2. Random-effects network meta-analysis was performed, and dichotomous data were pooled as odds ratios with 95% confidence intervals. The primary outcome was treatment success without modification; the secondary outcomes were adverse events (AEs), all-cause mortality, and new infections. The GRADE tool was used to assess the quality of the evidence. The protocol was registered with PROSPERO ID CRD42021226763.ResultsEighteen studies with 2517 patients were included. The results showed no statistically significant difference between the optional antipseudomonal β-lactams in the outcomes of treatment success without modification, all AEs, all-cause mortality, and new infections for pediatric FN. Based on the results of Bayesian rank probability, meropenem was ranked highest among all the treatment options with regard to treatment success without modification benefit; ceftazidime and meropenem were associated with a lower risk of AEs; cefoperazone/sulbactam and piperacillin/tazobactam were associated with a lower risk of mortality, and piperacillin/tazobactam and meropenem were associated with a lower risk of new infections. The quality of evidence was moderate.ConclusionsMeropenem and piperacillin/tazobactam were found to be better with regard to treatment success without modification, with a comparable safety profile. Therefore, our findings support the use of meropenem and piperacillin/tazobactam as a treatment option for pediatric FN patients.