mNGS for Therapy of Urinary Infectious Diseases

Urinary Tract Infections Clinical Trial

— PGS-U-UTI&UC  

Official title:

Pan-genome Sequencing of Urine Cell-free DNA for Therapy of Urinary Infectious Diseases: a Single Center Prospective Study Clinical Control Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05624476
• Other study ID #: CZGR2022002
• Status: Not yet recruiting
• Start date: January 1, 2023
• Est. completion date: December 31, 2023

Study information

• Verified date: November 2022
• Source: Shanghai Changzheng Hospital
• Contact: Xiaofeng Hang, Prof.
• Phone: +8613516063666
• Email: hangxfdoc[@]163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

Urinary tract infection is a common infectious disease in clinic. Urinary tract infection is easily caused by abnormal structure and function of urinary system, low immunity, pregnancy, gender and sexual activity, and iatrogenic factors. Urinary tract infection has a wide spectrum of pathogenic microorganisms, including Gram-negative bacilli, Gram-positive cocci, fungi, mycoplasma, chlamydia, viruses and so on. 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. At present, it is commonly used to collect midstream urine for pathogen culture in clinic, but it has the disadvantages of time-consuming and low detection rate, and the use of antibiotics can affect the results of culture.

Metagenomic sequencing has been widely used in clinical pathogen diagnosis, especially in difficult infectious diseases. Its principle is to collect samples, use mNGS to process the samples before sequencing, expose the nucleic acid, compare the nucleic acid sequence of pathogens with the designated huge biological database, and realize the comprehensive detection of viruses, bacteria, fungi, parasites and atypical microorganisms. Compared 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. However, mNGS has obvious advantages in clinical diagnosis, with high specificity and accuracy, and shorter detection time than traditional culture. In the aspect of mixed infection, because of its non-bias, the detection rate of multiple pathogens is higher than that of conventional culture, smear, PCR and other tests, which can detect other pathogens and even rare pathogens that can not be detected conventionally.

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. For example, there are many pathogens with high reading, and the test results are sorted to form a list of pathogens, but it is impossible to determine which or which pathogens are pathogenic. 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 72
• Est. completion date: December 31, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Sequelae of; Infection
• Urinary Tract Infections

Intervention

Diagnostic Test:
• mNGS of urine cell-free DNA
Metagenomic sequencing of urine cell-free DNA

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Changzheng Hospital

References & 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. Review. — View Citation

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. Review. — View Citation

Frimodt-Møller 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. — View Citation

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 — View Citation

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. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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