Microbial Threshold Guidelines for UTI Diagnosis: A Scoping Systematic Review

Figures & data

Table 1 cUTI Definition Used for Classification in This Review

Risk Factors and Examples of cUTI	References
* UTIs in the elderly due to increased risk associated with comorbidities and immunocompromised state	Sabih A, Leslie SW. Complicated Urinary Tract Infections. [Updated 2023 Jan 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Available from: https://www.ncbi.nlm.nih.gov/books/NBK436013/ Accessed June 5, 2023.^Citation14
* UTIs in patients with anatomic or functional pathology affecting the urinary tract, such as obstruction, hydronephrosis, renal tract calculi, or colovesical fistula
* UTIs in patients with an immune-compromised state, such as steroid use, post-chemotherapy, diabetes, or HIV
* UTIs in males
* UTIs occurring after instrumentation, nephrostomy tubes, ureteric stents, suprapubic tubes, or Foley catheters
* UTIs in renal transplant patients
* UTIs in patients with impaired renal function
* UTIs following prostatectomy or radiotherapy
* UTIs in patients with a history of recurrent UTIs	Wagenlehner FME, Johansen TEB, Cai T et al. Epidemiology, definition and treatment of complicated urinary tract infections. Nat Rev Urol. 2020;17(10):586–600.^Citation6
* Recurrent UTIs defined as at least two symptomatic episodes within six months or at least three symptomatic episodes within 12 months	Medina M, Castillo-Pino E. An introduction to the epidemiology and burden of urinary tract infections. Ther Adv Urology. 2019;11:1756287219832172.^Citation3
* UTIs caused by atypical microorganisms or multi-drug-resistant microorganisms. Typical UTI-causing microorganisms include Escherichia coli, Pseudomonas aeruginosa, several species within the Enterobacteriaceae family (Proteus and Klebsiella), and a few gram-positive bacteria, such as Staphylococcus saprophyticus and Enterococcus faecalis, as well as fungi, such as Candida species	Price TK, Hilt EE, Dune TJ, Mueller ER, Wolfe AJ, Brubaker L. Urine trouble: should we think differently about UTI? Int Urogynecol J. 2018;29(2):205–210.^Citation16
* UTIs that have possibly extended beyond the bladder (ie, UTI with fever or other systemic symptoms, suspected or documented pyelonephritis, and UTI with sepsis or bacteremia)	Gupta K. Acute complicated urinary tract infection (including pyelonephritis) in adults. [Updated 2023 May]. In: UpToDate [Internet]. The Netherlands: Wolters Kluwer. Available from: https://www.uptodate.com/contents/acute-complicated-urinary-tract-infection-including-pyelonephritis-in-adults Accessed June 5, 2023.^Citation15

Table 2 Final Calibrated Parameter Search for This Review

Parameter Search for Guidelines containing Diagnostic Microbial Thresholds for Urinary Tract Infection

((guidelines [Title/Abstract] OR consensus [Title/Abstract] OR evaluation [Title/Abstract] OR surveillance [Title/Abstract] OR perspective [Title/Abstract] OR recommendation [Title/Abstract]) NOT (pediatric [Title/Abstract] OR children[Title/Abstract] OR child [Title/Abstract]) AND (infection[Title/Abstract]) AND (“urinary tract” [All Fields]) AND (diagnosis [MeSH Terms] OR diagnosis [All Fields] OR diagnostic [All Fields] OR diagnostical [All Fields] OR diagnostically[All Fields] OR diagnostics[All Fields] OR diagnosable [All Fields] OR diagnosi [All Fields] OR diagnosis[MeSH Terms] OR diagnosis [All Fields] OR diagnose [All Fields] OR diagnosed [All Fields] OR diagnoses [All Fields] OR diagnosing[All Fields] OR diagnosis [MeSH Subheading] OR definite [All Fields] OR definitely [All Fields] OR definition [All Fields] OR definitional[All Fields] OR definitions [All Fields] OR definitive [All Fields] OR definitively[All Fields] AND (review [Publication Type] OR ‘review literature as topic’ [MeSH Terms] OR review [All Fields]) AND (humans [MeSH Terms]) AND (english [Language]) AND (1992/01/01:2023/01/31[Date – Publication]))

Figure 1 PRISMA flow diagram for this UTI guideline scoping review.

Notes: Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. Creative Commons. For more information, visit: http://www.prisma-statement.org/.

Figure 2 Complicated UTI (cUTI) microbial threshold recommendations by geographical region; CAUTI not included. The vertical axes indicate the region and number of guidelines. The horizontal axes indicate the number of recommendations. Guidelines often included more than one recommendation. Microbial thresholds in CFU/mL are indicated by color (none = navy blue, any count = yellow, 10¹ = pink, 10² = orange, 10³ = light blue, 10⁴ = green, 10⁵ = Oxford blue, and no consensus = khaki). Definition of cUTI used is outlined in Table 1.

Figure 3 Complicated UTI (cUTI) diagnostic microbial threshold recommendations by time period; CAUTI not included. The vertical axes indicate the eight-year time periods and the number of guidelines. The horizontal axes indicate the total recommendations from all guidelines. Microbial thresholds in CFU/mL are indicated by color (none = navy blue, any count = yellow, 10¹ = pink, 10² = orange, 10³ = light blue, 10⁴ = green, 10⁵ = Oxford blue, and no consensus = khaki).

Figure 4 Complicated UTI (cUTI) Diagnostic Microbial Threshold Recommendations by Diagnosis; CAUTI not included - Comparison Between Older and Newer Guidelines. The vertical axes indicate the number of guidelines per diagnosis group/time period. The horizontal axes indicate the percent of the total recommendations for that diagnosis group/time period. Microbial thresholds in CFU/mL are indicated by color (none = navy blue, any count = yellow, 10¹ = pink, 10² = orange, 10³ = light blue, 10⁴ = green, 10⁵ = Oxford blue, and no consensus = khaki). rUTI = recurrent Urinary Tract Infection.

Figure 5 Complicated UTI (cUTI) diagnostic microbial threshold recommendations by specimen collection method; CAUTI not included. The vertical axes indicate the collection method and number of guidelines. The horizontal axes indicate the percent of the total recommendations for each collection method. Microbial thresholds in CFU/mL are indicated by color (none = navy blue, any count = yellow, 10¹ = pink, 10² = orange, 10³ = light blue, 10⁴ = green, 10⁵ = Oxford blue, and no consensus = khaki). The “indwelling catheter” collection method includes collection via indwelling suprapubic catheter.

Figure 6 Complicated UTI (cUTI) Midstream Specimen Diagnostic Microbial Threshold Recommendations by Sex and Risk for Cystitis. The vertical axes indicate the sex-risk group and number of guidelines. The horizontal axes indicate the percent of the total recommendations for each group. Microbial thresholds in CFU/mL are indicated by color (none = navy blue, any count = yellow, 10¹ = pink, 10² = orange, 10³ = light blue, 10⁴ = green, 10⁵ = Oxford blue, and no consensus = khaki). High risk patients in the at risk categories included solid organ transplant, spinal cord injury, intensive care unit, and long-term care patients.

Table 3 Quality of Evidence – References Most Frequently Cited as Justification in the Guidelines

Publication/Author Team	Summary	Cited	Total Citations in Study Guidelines
Hooton, Roberts, Cox, Stapleton^Citation58	Escherichia coli in midstream urine was highly predictive of acute cystitis even at very low counts (10^2 CFU/mL).	7	18
Hooton, Bradley, Cardenas, Colgan, Geerlings, Rice, Saint, Schaeffer, Tambayh, Tenke, Nicolle^Citation26	2009 IDSA guidelines on diagnosis, prevention, and treatment of CAUTI recommend that in symptomatic patients with indwelling or intermittent catheterization a UTI is present if ≥10^3 CFU/mL of 1 or more bacterial species grow midstream within 48 hours of catheter removal.	6
Hooton^Citation57	The traditional criterion for a positive culture of voided urine (10^5 CFU/mL) is insensitive for bladder infection, and 30 to 50% of women with cystitis have colony counts of 10^2 to 10^4 CFU/mL in voided urine.	2
Hooton, Stamm^Citation55	Overview of the diagnosis and treatment of uncomplicated urinary tract infections in women and men. Microbial threshold level of 10^2 CFU/mL in acute uUTI cystitis and to 10^4 CFU/mL in pyelonephritis are diagnostically more specific and sensitive than the traditional 10^5 CFU/mL cutoff.	2
Stamm, Counts, Running, Fihn, Turck, Holmes^Citation62	In symptomatic women, 10^2 CFU/mL of coliforms in midstream urine had a high predictive value.	8	14
Stamm, Wagner, Amsel, Alexander, Turck, Counts, Holmes^Citation60	Bacteriuria of greater than or equal to 10^5 CFU/mL may be an insensitive diagnostic criterion when applied to symptomatic lower urinary tract infection in voided, catheter, and suprapubic urine.	3
Stamm, Hooton^Citation61	Antibiotic treatments and diagnostic criteria, including microbial thresholds, for different types of UTIs are distinct.	2
Kass^Citation64	In approximately 95% of pyelonephritis patients, 10^5 CFU/mL were cultured from voided or catheterized urine.	5	12
Kass^Citation66,Citation67	In most cases, >10^5 CFU/mL in urine collected via catheterization indicates the presence of true bacteriuria, that is, of actual multiplication of bacteria within the urinary tract, in pregnancy. Conversely, bacterial colony counts <10^5 CFU/mL usually represent contamination upon the collection of the specimen. (Originally published by Kass 1956^Citation66 and reprinted in 2002^Citation67)	4
Kass^Citation65	Based on the >10^5 CFU/mL threshold*, 6–7% of pregnant women have bacteriuria in voided urine specimens which leads to pyelonephritis in 40% of those women. *this threshold is based on evidence from a prior publication by Kass^Citation66	2
Nicolle, Ronald, Gupta, Bradley, Colgan, DeMuri, Drekonja, Eckert, Geerlings, Köves, Hooton, Juthani-Mehta, Knight, Saint, Schaeffer, Trautner, Wullt, Siemieniuk, Rice, Schaeffer^Citation68–75	*	1	8
Kunin, White, Hua^Citation78	E. coli and Staphylococcus saprophyticus were associated with urinary symptoms and pyuria at 10^2–10^4 CFU/mL in clean-catch midstream urine specimens. As bacterial counts increased, so did symptoms and pyuria. Authors concluded this may be an early phase of UTI.	4	7
Kunin^Citation77	Using a clean, freshly voided urine specimen, UTI patients will usually have counts of >10^5 CFU/mL of uropathogens. Contamination with commensal microorganisms is usually associated with counts of <10^3 CFU/mL. Counts of 10^3 to 10^5 CFU/mL are significant when combined with symptoms and pyuria. Certain bacterial species grow slowly and an appropriate range for significant bacteriuria with these organisms may reach counts of only 10^4 to 10^5 CFU/mL. The tubercle bacillus and systemic fungi grow poorly in urine and are considered significant at any count. Fastidious bacteria require special culture media and will not be detected by routine cultures.	2
Stark, Maki^Citation76	Patients with indwelling catheters that cultured <10^5 CFU/mL typically grew >10^5 CFU/mL within 3 days of first culture. Concluded catheterized patients are highly susceptible to UTI and low microbial concentrations may be clinically and epidemiologically important.	6	6
Rubin, Shapiro, Andriole, Davis, Stamm^Citation51	For clinical trial patients testing UTI antimicrobial therapy, proposed using microbial levels of ≥10^3 CFU/mL for acute uncomplicated cystitis, ≥10^4 CFU/mL for pyelonephritis and UTI in men, and ≥10^5 CFU/mL for complicated UTI, in midstream urine specimens, for enrollment.	4	5
Doherty, NIDRR^Citation54	Spinal cord injury patients with signs or symptoms should be considered as having a UTI when ≥10^2 CFU/mL is cultured from a catheter-derived specimen, or ≥10^4 CFU/mL is cultured from clean void specimens obtained from males using condom devices. Any detectable count cultured from urine specimens taken from an indwelling catheter should be considered a UTI.	4	4
Sobel^Citation81	Diagnostic and clinical criteria for candiduria have not been established.	2	4
Lipsky, Ireton, Fihn, Hackett, Berger^Citation84	Urine specimens from suprapubic aspiration or urethral catheterization had excellent agreement to clean catch midstream and uncleansed first void specimens. A threshold of ≥10^3 CFU/mL in men is a good criterion for UTI.	3	3
Giesen, Cousins, Dimitrov, van de Laar, Fahey^Citation85	A systematic review showed predicting UTI using symptoms with diagnostic thresholds of 10^2, 10^3, and 10^5 CFU/mL in clean-catch or catheterized urine specimens were most sensitive at lower microbial levels to rule in presence of a UTI.	3	3
Epp, Larochelle^Citation86	10^5 CFU/mL from midstream urine specimens is considered the UTI criterion, but 10^3 CFU/mL is more sensitive and acceptable Women with growth aside from E. coli and/or persistent hematuria should be evaluated under cystoscopy and imaging.	3	3
Roberts^Citation88	Significant UTIs may be associated with counts of <10^5 CFU/mL, especially in patients with no other source of infection.	2	3
Hovelius, Mardh, Bygren^Citation89	In this study, UTIs with Staphylococcus saprophyticus had a recurrence again in >50% of subjects, most of whom also had renal associated symptoms. The demonstration of S. saprophyticus in voided urine specimens, even in counts of <10^4 bacteria per mL may be a significant finding.	2	2
Savage, Hajj, Kass^Citation90	Use of 10^5 CFU/mL in pregnant women may be linked to early labor and delivery.	2	2
Gribble, McCallum, Schechter^Citation91	The traditional ≥10^5 CFU/mL diagnostic threshold for UTI had an unacceptably low sensitivity for spinal cord injury patients compared to suprapubic aspirations. For gram-positive bacteria, ≥10^1 and ≥10^2 CFU/mL had good sensitivity and specificity. For gram-negative bacteria, ≥10^1 was ideal, but ≥10^2 CFU/mL was sufficient for urine specimens from suprapubic aspiration.	2	2
Platt, Polk, Murdock, Rosner^Citation92,Citation93	*	1	2
Johnson, Stamm^Citation94,Citation95	*	1	2
Naber, Schito, Botto, Palou, Mazzei, Fünfstück, Hofstetter, Brühl, Hoyme^Citation96,Citation97	*	1	2
Fihn, Johnson, Stamm^Citation98,Citation99	*	1	2

Note: *There is no summary because multiple articles were cited only once but came from a frequently cited author and team.

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