mNGS for Therapy of Urinary Infectious Diseases

NCT05624476 | Unknown DMC

• 1 other identifier: CZGR2022002
• Study Type: observational
• Target: 72
• Locations: 0 countries
• Sites: N/A

Brief Summary

Urinary tract infection is a common infectious disease in clinic. Although urinary tract infection can be initially diagnosed by clinical sign and symptom, signs and urine routine, the application of appropriate antibiotic therapy depends on the further identification of pathogens. Metagenomic sequencing has been widely used in clinical pathogen diagnosis, especially in difficult infectious diseases. ICompared with tissue samples, cerebrospinal fluid, bronchoalveolar lavage fluid, whole blood and other samples, the application of mNGS in urine samples is relatively limited because incorrect sampling methods before and after collection of urine samples are easy to contaminate the samples and the colonization of distal urethra, periurethral skin and vagina will interfere with the interpretation of reports. Previous small sample studies have shown that the sensitivity of mNGS in urinary tract infection is high, but the specificity is relatively low, and there are many problems such as difficult interpretation of reports and low clinical conformity. This is closely related to the mNGS technology algorithm, such as the inability to eliminate the influence of urinary system background bacteria, and the ambiguity of short sequence alignment, which makes it difficult to distinguish homologous pathogens. In this study, based on the standard mNGS sequencing process, the improved Z value analysis method was used to select strictly enrolled clinical samples and compare them with pathogen culture to observe the clinical value of mNGS with Z value analysis method in the treatment of urinary tract infection.

Conditions

Urinary Tract Infections; Sequelae of; Infection

Outcome Measures

Primary Outcomes (1)

• Number of participants cured from urinary tract infection

  The "cure" is defined as "The clinical symptom of urinary tract infection disappeared and the urine tests returned to normal"

  17 days

Study Arms (2)

experimental group

Patients with urinary tract infection received treatments guided by both culture and mNGS

Diagnostic Test: mNGS of urine cell-free DNA

control group

Patients with urinary tract infection received treatments guided by culture first

Diagnostic Test: mNGS of urine cell-free DNA

Interventions

mNGS of urine cell-free DNA DIAGNOSTIC_TEST

Metagenomic sequencing of urine cell-free DNA

control group; experimental group

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with urinary tract infection, which is caused by abnormal structure and function of urinary system, low immunity, pregnancy, gender and sexual activity, and iatrogenic factors, with a wide spectrum of pathogenic microorganisms, including Gram-negative bacilli, Gram-positive cocci, fungi, mycoplasma, chlamydia, viruses and so on, and diagnosed by clinical sign and symptom, signs and urine routine.

You may qualify if:

• Age: 16-70 years.
• Typical symptoms of urinary tract infection + pyuria (WBC ≥ 10/HP in urine sediment after centrifugation).
• Clinical diagnosis: acute cystitis, urethritis, acute and chronic prostatitis, pyelonephritis, epididymitis; or complex urinary tract infection, such as urinary tract deformity, obstruction, double J tube, etc.
• Sign the informed consent form voluntarily.

You may not qualify if:

• Malignant tumors of liver or other organs or previous history of tumors.
• Complicated with gastrointestinal bleeding, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome and acute infection.
• Patients with severe heart, lung, kidney or blood system diseases and failure.
• Pregnant or breastfeeding women.
• Allergic constitution.
• Those who have a history of alcoholism and drug abuse and fail to give up effectively.
• The subject withdrew from the study on the condition that he/she had not participated in other clinical trials within 4 weeks.
• Other conditions which, in the opinion of the investigator, are not suitable for participation in the study.
• Antibiotic therapy was performed in the past month because of urinary tract infection.
• Broad-spectrum antibiotic therapy has been performed for other uncontrollable infections or other infections.

Sponsors & Collaborators

• Shanghai Changzheng Hospital: lead

Related Publications (6)

• Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015 May;13(5):269-84. doi: 10.1038/nrmicro3432. Epub 2015 Apr 8.

  PMID: 25853778 RESULT

• Frimodt-Moller N. The urine microbiome - Contamination or a novel paradigm? EBioMedicine. 2019 Jun;44:20-21. doi: 10.1016/j.ebiom.2019.05.016. Epub 2019 May 14. No abstract available.

  PMID: 31101594 RESULT

• Janes VA, Matamoros S, Munk P, Clausen PTLC, Koekkoek SM, Koster LAM, Jakobs ME, de Wever B, Visser CE, Aarestrup FM, Lund O, de Jong MD, Bossuyt PMM, Mende DR, Schultsz C. Metagenomic DNA sequencing for semi-quantitative pathogen detection from urine: a prospective, laboratory-based, proof-of-concept study. Lancet Microbe. 2022 Aug;3(8):e588-e597. doi: 10.1016/S2666-5247(22)00088-X. Epub 2022 Jun 7.

  PMID: 35688170 RESULT

• Foxman B. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am. 2014 Mar;28(1):1-13. doi: 10.1016/j.idc.2013.09.003. Epub 2013 Dec 8.

  PMID: 24484571 RESULT

• Mitchell SL, Simner PJ. Next-Generation Sequencing in Clinical Microbiology: Are We There Yet? Clin Lab Med. 2019 Sep;39(3):405-418. doi: 10.1016/j.cll.2019.05.003.

  PMID: 31383265 RESULT

• Zeng S, Ying Y, Xing N, Wang B, Qian Z, Zhou Z, Zhang Z, Xu W, Wang H, Dai L, Gao L, Zhou T, Ji J, Xu C. Noninvasive Detection of Urothelial Carcinoma by Cost-effective Low-coverage Whole-genome Sequencing from Urine-Exfoliated Cell DNA. Clin Cancer Res. 2020 Nov 1;26(21):5646-5654. doi: 10.1158/1078-0432.CCR-20-0401. Epub 2020 Oct 9.

  PMID: 33037018 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

free cfDNA of pathogens in urine

MeSH Terms

Conditions

Urinary Tract Infections; Infections

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Junxue Wang, Prof.

  Changzheng Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaofeng Hang, Prof.

CONTACT

+8613516063666; hangxfdoc@163.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2022
• First Posted: November 22, 2022
• Study Start: January 1, 2023
• Primary Completion: September 30, 2023
• Study Completion: December 31, 2023
• Last Updated: November 22, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share