Fast and precise pathogen detection and identification of overlapping infection in patients with CUTI based on metagenomic next-generation sequencing

Abstract

Rationale: The gold standard for pathogen detection and identification of complicated urinary tract infection (CUTI) remains quantitative urine culture, however, the diagnostic value of urine culture remains limited due to the time-consuming procedure and low detection rate. Here we report a case of successfully using Metagenomic next-generation sequencing (mNGS) provided fast and precise detection and identification of overlapping infection in patients with CUTI with no similar reports or studies published before to the best of our knowledge. Patient concerns: A 70-year-old male was admitted to hospital due to elevated serum creatinine for 2 weeks. Diagnoses: Acute exacerbation of chronic renal failure and CUTI were the most critical diagnosis on admission. Interventions: Blood purification, bladder irrigation and aggressive anti-infective therapy were administered. But the empirical anti-infection therapy and the adjustment of treatment according to the evidence of urine culture drug sensitivity had no obvious effect. We further carried out urinary PMseq-DNA detection and the results showed overlapping infection with Enterococcus faecium, Enterococcus hirae, Pseudomonas aeruginosa, Pseudomonas denitrificans and Candida albicans. According to the genetic test results, linezolid, meropenem and fluconazole triple anti-infection treatment was given. Outcomes: After adjusting the treatment, the infection was basically controlled in 10 days, and even the renal function was significantly improved, dialysis independence was achieved after 3 months. Lessons: Our case illustrated the potential application of mNGS in detecting pathogenic microorganisms in patients with CUTI especially when overlapping infections are present.

Enhancing urinary tract infection diagnosis for negative culture patients with metagenomic next-generation sequencing (mNGS)

“…Clinically, complicated UTIs are defined as those associated with factors that compromise the urinary tract or host defense, including urinary tract obstruction, immunosuppression, renal failure, and foreign bodies such as indwelling urinary catheters or other drainage devices (Lichtenberger and Hooton, 2008;Levison and Kaye, 2013). In our cases, the majority of patients had complicated UTI that showed recurrent, persistent and refractory features similar to the previous reports (Zhang et al, 2021).…”

“…The applications of mNGS on non-sterile materials (e.g., urine) remains are still scarce and controversial. In one of the few recent studies on urine (Zhang et al, 2021;Zhang et al, 2022), a prospective proof-ofconcept study by Janes, V. A and colleagues confirmed the feasibility of metagenomic sequencing in detecting of urinary pathogens and drug resistance (Janes et al, 2022). We conducted a mNGS study in patients with suspected UTI and compared it with conventional test in terms of diagnostic performance, pathogenic findings to demonstrate its significance.…”

Literature Review of Pathogen Agnostic Molecular Testing of Clinical Specimens From Difficult-to-Diagnose Patients: Implications for Public Health

“…Metagenomic techniques were used to successfully identify pathogens directly from patient specimens, including cerebrospinal fluid, 13 , 17-25 respiratory secretions, 26-31 skin and soft tissue or bone and joint tissues/synovial fluid, 32 , 34 heart valve tissue, 35 and urine. 36 A review of the methods sections revealed significant heterogeneity in sensitivity and specificity of testing due to variability in study design, reference standards, clinical factors, and technical variation among the laboratories performing the testing. For exemplar US publications, laboratories of the University of California at San Francisco were featured prominently as testing laboratories.…”