670. Precision Metagenomic (PM) Sequencing Outperforms Conventional Urine Culture in Detecting Clinically Relevant Microorganisms

Czakó, Rita; Kent, B.A.; Mangifesta, Marta; Kadam, Anagha; Xie, Heng; Stauffer, Stacie; Lemon, Jamie; Briggs, Benjamin; Farnaes, Lauge; Salais, Robert

doi:10.1093/ofid/ofab466.867

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“…As an example, C. coyleae infection in a polycystic kidney disease patient led to bilateral nephrectomy, suggesting that Corynebacterium is an emerging pathogen with the potential for complicated UTIs (Barberis et al, 2018). Two viruses were detected by PM and classified in phenotypic group-1-Epstein-Barr virus and JC polyomavirus-both unlikely to be (Greub and Raoult, 2002), PCR (Reploeg et al, 2001), and PM (Goldberg et al, 2015); (B) microorganisms detected by culture (Duan et al, 2022), PCR (Stinnett et al, 2021), and PM (62). Note: detected by routine microbiology or PCR.…”

Section: Comparative Resultsmentioning

confidence: 99%

“… Differential detection of microorganisms by urine culture, PCR, and PM in UTI samples (n = 47). (A) Number of samples positive (≥1 organism detected) by culture ( Greub and Raoult, 2002 ), PCR ( Reploeg et al., 2001 ), and PM ( Goldberg et al., 2015 ); (B) microorganisms detected by culture ( Duan et al., 2022 ), PCR ( Stinnett et al., 2021 ), and PM (62). Note: (A) represents 33 samples concordantly positive by culture, PCR, and NGS; one sample only positive by PCR; eight samples only positive by PM; five samples positive by PCR and NGS but not by culture.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, extracting clinically relevant information can be challenging for target-agnostic approaches—based on rRNA gene amplification and shotgun sequencing after the depletion of host DNA—that promote a high microbiome yield ( Price et al., 2021 ). Alternatively, a hybridization capture-based targeted sequencing approach, also known as precision metagenomics (PM), has potential to bridge the diagnostic gap by providing enhanced discovery power with better diagnostic yield without diluting clinically relevant information ( Cariou et al., 2018 )—also enabling important uropathogen discovery including fastidious, obligate anaerobic, and non-culturable microorganisms ( Stinnett et al., 2021 ). Accordingly, PM has potential to overcome limitations of both routine and robust UTI testing methods directly from clinical samples.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Advantage of precision metagenomics for urinary tract infection diagnostics

Almas¹,

Carpenter

Rowan³

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundUrinary tract infections (UTIs) remain a diagnostic challenge and often promote antibiotic overuse. Despite urine culture being the gold standard for UTI diagnosis, some uropathogens may lead to false-negative or inconclusive results. Although PCR testing is fast and highly sensitive, its diagnostic yield is limited to targeted microorganisms. Metagenomic next-generation sequencing (mNGS) is a hypothesis-free approach with potential of deciphering the urobiome. However, clinically relevant information is often buried in the enormous amount of sequencing data.MethodsPrecision metagenomics (PM) is a hybridization capture-based method with potential of enhanced discovery power and better diagnostic yield without diluting clinically relevant information. We collected 47 urine samples of clinically suspected UTI and in parallel tested each sample by microbial culture, PCR, and PM; then, we comparatively analyzed the results. Next, we phenotypically classified the cumulative microbial population using the Explify® data analysis platform for potential pathogenicity.ResultsResults revealed 100% positive predictive agreement (PPA) with culture results, which identified only 13 different microorganisms, compared to 19 and 62 organisms identified by PCR and PM, respectively. All identified organisms were classified into phenotypic groups (0–3) with increasing pathogenic potential and clinical relevance. This PM can simultaneously quantify and phenotypically classify the organisms readily through bioinformatic platforms like Explify®, essentially providing dissected and quantitative results for timely and accurate empiric UTI treatment.ConclusionPM offers potential for building effective diagnostic models beyond usual care testing in complex UTI diseases. Future studies should assess the impact of PM-guided UTI management on clinical outcomes.

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