Skip to main content

Urinary microbiota of women with recurrent urinary tract infection: collection and culture methods

Abstract

Introduction and hypothesis

Many clinicians utilize standard culture of voided urine to guide treatment for women with recurrent urinary tract infections (RUTI). However, despite antibiotic treatment, symptoms may persist and events frequently recur. The cyclic nature and ineffective treatment of RUTI suggest that underlying uropathogens pass undetected because of the preferential growth of Escherichia coli. Expanded quantitative urine culture (EQUC) detects more clinically relevant microbes. The objective of this study was to assess how urine collection and culture methods influence microbial detection in RUTI patients.

Methods

This cross-sectional study enrolled symptomatic adult women with an established RUTI diagnosis. Participants contributed both midstream voided and catheterized urine specimens for culture via both standard urine culture (SUC) and EQUC. Presence and abundance of microbiota were compared between culture and collection methods.

Results

Forty-three symptomatic women participants (mean age 67 years) contributed specimens. Compared to SUC, EQUC detected more unique bacterial species and consistently detected more uropathogens from catheterized and voided urine specimens. For both collection methods, the most commonly detected uropathogens by EQUC were E. coli (catheterized: n = 8, voided: n = 12) and E. faecalis (catheterized: n = 7, voided: n = 17). Compared to catheterized urine samples assessed by EQUC, SUC often missed uropathogens, and culture of voided urines by either method yielded high false-positive rates.

Conclusions

In women with symptomatic RUTI, SUC and assessment of voided urines have clinically relevant limitations in uropathogen detection. These results suggest that, in this population, catheterized specimens analyzed via EQUC provide clinically relevant information for appropriate diagnosis.

This is a preview of subscription content, access via your institution.

Fig. 1

References

  1. Aslam S, Albo M, Brubaker L. Recurrent urinary tract infections in adult women. JAMA. 2020;323(7):658–9.

    Article  Google Scholar 

  2. Gaitonde S, Malik RD, Zimmern PE. Financial burden of recurrent urinary tract infections in women: a time-driven activity-based cost analysis. Urol. 2019;128:47–54.

    Article  Google Scholar 

  3. Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J, Monga A, Petri E, Rizk DE, Sand PK, Schaer GN. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Int Urogynecol J. 2010;21:5–26.

    Article  Google Scholar 

  4. Kass EH. Asymptomatic infections of the urinary tract. Trans Assoc Am Phys. 1956;69:56–64.

    CAS  PubMed  Google Scholar 

  5. Kass EH. Bacteriuria and the diagnosis of infections of the urinary tract; with observations on the use of methionine as a urinary antiseptic. AMA Arch Intern Med. 1957;100(5):709–14.

    Article  CAS  Google Scholar 

  6. Price TK, Hilt EE, Dune TJ, Mueller ER, Wolfe AJ, Brubaker L. Urine trouble: should we think differently about UTI? Int Urogynecol J. 2017;29(2):205–10.

    Article  Google Scholar 

  7. Price TK, Dune T, Hilt EE, et al. The clinical urine culture: enhanced techniques improve detection of clinically relevant microorganisms. J Clin Microbiol. 2016;54(5):1216–22.

    Article  CAS  Google Scholar 

  8. Scott VC, Haake DA, Churchill BM, Justice SS, Kim JH. Intracellular bacterial communities: a potential etiology for chronic lower urinary tract symptoms. Urol. 2015;86(3):425–31.

    Article  Google Scholar 

  9. Chen YB, Hochstedler B, Pham TT, Alvarez MA, Mueller ER, Wolfe AJ. The urethral microbiota: a missing link in the female urinary microbiota. J Urol. 2020;204(2):303–9.

    Article  Google Scholar 

  10. Kline KA, Lewis AL. Gram-positive uropathogens, polymicrobial urinary tract infection, and the emerging microbiota of the urinary tract. Microbiol Spectr. 2016;4(2). https://doi.org/10.1128/microbiolspec.UTI-0012-2012.

  11. Khoshnood S, Heidary M, Mirnejad R, Bahramian A, Sedighi M, Mirzaei H. Drug-resistant gram-negative uropathogens: a review. Biomed Pharmacother. 2017;94:982–94.

    Article  CAS  Google Scholar 

  12. Fisher JF, Kavanagh K, Sobel JD, Kauffman CA, Newman CA. Candida urinary tract infection: pathogenesis. Clin Infect Dis. 2011;52(suppl_6):S437–51.

    Article  Google Scholar 

  13. Whiteside SA, Razvi H, Dave S, Reid G, Burton JP. The microbiome of the urinary tract—a role beyond infection. Nat Rev Urol. 2015;12(2):81–90.

    Article  Google Scholar 

  14. Gerber D, Forster CS, Hsieh M. The role of the genitourinary microbiome in pediatric urology: a review. Curr Urol Rep. 2018;19(1):13.

    Article  Google Scholar 

  15. Horsley H, Malone-Lee J, Holland D, et al. Enterococcus faecalis subverts and invades the host urothelium in patients with chronic urinary tract infection. PLoS One. 2013;8(12):e83637.

    Article  Google Scholar 

  16. Whiteside SA, Dave S, Seney SL, Wang P, Reid G, Burton JP. Enterococcus faecalis persistence in pediatric patients treated with antibiotic prophylaxis for recurrent urinary tract infections. Future Microbiol. 2018;13:1095–115.

    Article  CAS  Google Scholar 

  17. Horsley H, Dharmasena D, Malone-Lee J, Rohn JL. A urine-dependent human urothelial organoid offers a potential alternative to rodent models of infection. Sci Rep. 2018;8:1238.

    Article  Google Scholar 

  18. Kodner CM, Thomas Gupton EK. Recurrent urinary tract infections in women: diagnosis and management. Am Fam Physician. 2010;82:638–43.

    PubMed  Google Scholar 

  19. Lifshitz E, Kramer L. Outpatient urine culture: does collection technique matter? Arch Intern Med. 2000;160(16):2537–40.

    Article  CAS  Google Scholar 

  20. Baerheim A, Digranes A, Hunskaar S. Evaluation of urine sampling technique: bacterial contamination of samples from women students. Br J Gen Pract. 1992;42(359):241–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Southworth E, Hochstedler B, Price TK, Joyce C, Wolfe AJ, Mueller ER. A cross-sectional pilot cohort study comparing standard urine collection to the peezy midstream device for research studies involving women. Female Pelvic Med Reconstr Surg. 2019;25(2):e28–33.

    Article  Google Scholar 

  22. Waller TA, Pantin SAL, Yenior AL, Pujalte GGA. Urinary tract infection antibiotic resistance in the United States. Prim Care. 2018;45(3):455–66.

    Article  Google Scholar 

  23. Hirakawa H, Suzue K, Kurabayashi K, Tomita H. The Tol-pal system of uropathogenic Escherichia coli is responsible for optimal internalization into and aggregation within bladder epithelial cells, colonization of the urinary tract of mice, and bacterial motility. Front Microbiol. 2019;10:1827.

    Article  Google Scholar 

  24. Anderson GG, Palermo JJ, Schilling JD, Roth R, Heuser J, Hultgren SJ. Intracellular bacterial biofilm-like pods in urinary tract infections. Sci. 2003;301:105–7.

    Article  CAS  Google Scholar 

  25. Wright KJ, Seed PC, Hultgren SJ. Development of intracellular bacterial communities of uropathogenic Escherichia coli depends on type 1 pili. Cell Microbiol. 2007;9(9):2230–41.

    Article  CAS  Google Scholar 

  26. Tapiainen T, Hanni AM, Salo J, Ikäheimo I, Uhari M. Escherichia coli biofilm formation and recurrences of urinary tract infections in children. Eur J Clin Microbiol Infect Dis. 2014;33(1):111–5.

    Article  CAS  Google Scholar 

  27. Durkin MJ, Keller M, Butler AM, Kwon JH, Dubberke ER, Miller AC, Polgreen PM, Olsen MA. An assessment of inappropriate antibiotic use and guideline adherence for uncomplicated urinary tract infections. Open Forum Infect Dis. 2018;5(9):ofy198.

    Article  Google Scholar 

  28. Zalewska-Piątek BM, Piątek RJ. Alternative treatment approaches of urinary tract infections caused by uropathogenic Escherichia coli strains. Acta Biochim Pol. 2019;66(2):129–38.

    PubMed  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge funding by NIH/NICHD R01 DK104718 (Drs. Wolfe and Brubaker) for support for the conduct of this research. For this study, no funding, supplies, or services were received from any commercial organization.

Author information

Authors and Affiliations

Authors

Contributions

BR Hochstedler and L Burnett: Data collection, Data management, Data analysis, Manuscript writing/editing, and Overall study supervision.

TK Price and C Jung: Protocol/project development, Data collection, Manuscript editing.

AJ Wolfe and L Brubaker: Protocol/project development, Data analysis, Overall study supervision, and Manuscript editing.

Corresponding author

Correspondence to Alan J. Wolfe.

Ethics declarations

Conflicts of interest

Dr. Wolfe discloses research support from the NIH, the DOD and Kimberly Clark Corporation. He also discloses membership on the Scientific Advisory Boards of Pathnostics and Urobiome Therapeutics. Dr. Brubaker discloses research funding from NIH and editorial stipends from Female Pelvic Medicine & Reconstructive Surgery, UpToDate, and JAMA. The remaining authors report no disclosures.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 25 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hochstedler, B.R., Burnett, L., Price, T.K. et al. Urinary microbiota of women with recurrent urinary tract infection: collection and culture methods. Int Urogynecol J 33, 563–570 (2022). https://doi.org/10.1007/s00192-021-04780-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00192-021-04780-4

Keywords

  • Enhanced urine culture
  • Recurrent urinary tract infection
  • Urine collection
  • Urinary microbiome
  • Urinary pathogen detection