Bacteriuria is the presence of bacteria in the urine. Urinary tract infections (UTIs) can occur in the urinary system and can be either symptomatic or asymptomatic. UTIs can include cystitis, an infection of the bladder or lower urinary tract; pyelonephritis, an infection of the upper urinary tract or kidney; urosepsis; urethritis; and male-specific conditions, such as bacterial prostatitis and epididymitis (Bonkat et al., 2024; Hooton & Gupta, 2023). Typically, in an infected person, bacteriuria, and pyuria (the presence of pus in the urine) are present and can be present in both symptomatic and asymptomatic UTIs. A urine culture can be performed to determine the presence of bacteria and to characterize the bacterial infection (Meyrier, 2024).

For guidance on pathogen panel testing from urine samples, please see CAM 181 Pathogen Panel Testing.

Regulatory Status
Since 1978, the FDA has approved several urine culture kits and devices (FDA, 2018). Additionally, many labs have developed specific urine culture tests that they must validate and perform in house. These laboratory-developed tests (LDTs) are regulated by the Centers for Medicare & Medicaid Services (CMS) as high-complexity tests under the Clinical Laboratory Improvement Amendments of 1988 (CLIA ’88). As an LDT, the U.S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use.

Policy  
Application of coverage criteria is dependent upon an individual’s benefit coverage at the time of the request.

1. For pregnant individuals, urine culture testing (with isolate identification and antibiotic susceptibilities if applicable) for a urinary tract infection (UTI) is considered MEDICALLY NECESSARY.
2. For asymptomatic individuals undergoing urological interventions which breach the mucosa,urine culture testing (with isolate identification and antibiotic susceptibilities if applicable) prior to the procedure is considered MEDICALLY NECESSARY.
3. For individuals exhibiting at least one sign or symptom of a possible UTI or bacteriuria (see Note 1 below), urine culture testing (with isolate identification and antibiotic susceptibilities if applicable) is considered MEDICALLY NECESSARY.
4. To assess pyelonephritis, urine culture testing (with isolate identification and antibiotic susceptibilities if applicable) is considered MEDICALLY NECESSARY.
5. For all other instances of asymptomatic UTI or asymptomatic bacteriuria not described above, urine culture testing (with isolate identification and antibiotic susceptibilities if applicable) is considered NOT MEDICALLY NECESSARY.
6. For individuals that show evidence of clinical resolution of infection, follow-up urine culture testing for an uncomplicated UTI is considered NOT MEDICALLY NECESSARY.

The following does not meet coverage criteria due to a lack of available published scientific literature confirming that the test(s) is/are required and beneficial for the diagnosis and treatment of an individual’s illness.

7. Urine culture testing (with isolate identification and antibiotic susceptibilities if applicable) is considered NOT MEDICALLY NECESSARY in any of the following situations:
   1. As a part of initial screening for asymptomatic prostatitis.
   2. As a part of assessment or prognosis of prostate biopsy.

NOTES:

Note 1:  Signs and symptoms of UTI/bacteriuria include (CDC, 2024)

• Fever
• Urgency to urinate
• Feeling the need to urinate despite having an empty bladder
• Increased frequency of urination
• Dysuria
• Suprapubic tenderness
• Pyuria
• Hematuria
• Cloudy urine
• Lower Back and Side (flank) pain
• Nausea
• Vomiting
• Chills
• Night sweats
• Pelvic pressure
• Change in urine smell
• Abnormal urinalysis findings

Table of Terminology

Rationale
Urinary tract infections (UTIs) can be either symptomatic or asymptomatic and can be classified as uncomplicated or complicated. Uncomplicated UTIs are “acute, sporadic or recurrent cystitis limited to non-pregnant [individuals] with no known relevant anatomical and functional abnormalities within the urinary tract or comorbidities” (Bonkat et al., 2024). All other UTIs that are not defined as uncomplicated are complicated UTIs. Complicated UTIs include “UTIs in a patient with an increased chance of a complicated course: i.e., all men, pregnant [individuals], patients with relevant anatomical or functional abnormalities of the urinary tract, indwelling urinary catheters, renal diseases, and/or with other concomitant immunocompromising diseases for example, diabetes” (Bonkat et al., 2024). Escherichia coli is the most common cause of complicated UTIs; however, “other uropathogens include other Enterobacteriaceae (such as Klebsiella spp and Proteus spp), Pseudomonas, enterococci, and staphylococci (methicillin-sensitive Staphylococcus aureus [MSSA] and methicillin-resistant S. aureus [MRSA])” (Hooton & Gupta, 2023). Even though both bacteriuria and pyuria are often present in UTIs, their presence alone is not indicative of a symptomatic infection. 

The presence of bacteriuria does not guarantee negative outcomes for a patient. In fact, the paradigm of the sterility of the bladder environment has changed over recent years. At least for females, the presence of female urinary microbiota (FUM) is believed to occur naturally and has been documented using sensitive bacterial DNA screening tests on asymptomatic females (Brubaker & Wolfe, 2016). Beneficial microbes, such as vaginal strains of Lactobacillus, can inhibit the grown of uropathogenic bacteria, including E. coli (Aroutcheva et al., 2001; Brubaker & Wolfe, 2016). Over-prescribing antibiotics, especially in cases of asymptomatic bacteriuria, can lead to both an eradication of beneficial bacterial flora and an emergence of antibiotic-resistant bacteria. Prescribing antibiotics as a prophylactic measure or in the instance of asymptomatic bacteriuria is detrimental because it is of limited value and can also increase incidences of drug-resistance. A study in 2002 by Harding and colleagues show that antibiotic treatment in diabetic individuals with asymptomatic bacteriuria did not result in a decrease of future symptomatic UTIs as compared to the control group; in fact, the experimental group had higher rates of adverse antimicrobial reactions (Harding et al., 2002). Even though the evidence-based guidelines by various societies, such as the EAU (Bonkat et al., 2024) and SHEA (SHEA, 2019), do not recommend performing urine testing or treatment for asymptomatic bacteriuria, inappropriate treatment is still occurring; in fact, one study by Cope and colleagues show that 32% of catheter-associated cases of asymptomatic bacteriuria and asymptomatic UTI received inappropriate treatment (Cope et al., 2009). The Antimicrobial Resistance Epidemiological Survey on Cystitis (ARESC) shows that up to 10.3% of E. coli in UTIs are “resistant to at least three different classes of antimicrobial agents” with ampicillin having the highest degree of resistance (48.3%). This is a large study of 4264 individuals from ten different countries to show that antibiotic-resistance is of international importance (Schito et al., 2009). 

Analytical Validity
Urinalysis (UA) to detect nitrite and leukocyte esterase to indicate the presence of bacteria is an accepted laboratory practice. One report, though, has shown that the use of nitrite has “a sensitivity of 3%, a specificity of 97%, and a negative predictive value of 55%” (Cooper et al., 1992). A 2004 meta-analysis study asserts that the “sensitivities of the combination of both tests vary between 68 and 88% in different patient groups, but positive test results have to be confirmed” (Devillé et al., 2004). They did note that the accuracy of the leukocyte esterase testing was higher in urology patients with a diagnostic odds ratio (DOR) of 276 as compared to the accuracy of nitrites (for example, in elderly patients DOR = 108) (Devillé et al., 2004).

Urine culture is considered a “gold standard” for detecting the presence of bacteria in urine (Graham & Galloway, 2001; Schmiemann et al., 2010). That being said, “the interpretation of culture results can be considered as more of an art than a science. A urine culture result depends on so many variables, such as appropriate collection, transport, and the limits of the methods of detection. The reliability of single positive urine culture in diagnosing UTI is only 80%, rising to 90% if a repeat culture shows identical results” (Graham & Galloway, 2001). This is using the definition of bacteriuria as being 105 bacteria/ml of urine. 

A potential future alternative to the urine culture could be multiplex PCR-based molecular testing, which Wojno et al. (2020) had found to be noninferior to urine culture for detection and identification of the bacteria. Agreement between the two testing methods was 90%, which exceeded the 85% noninferiority threshold. The multiplex PCR was also able to detect bacteria in 36% of symptomatic patients who had negative urine cultures and detected more polymicrobial infections than urine culture in a shorter amount of time (6 hours vs 48 hours for urine culture) (Wojno et al., 2020). 

Clinical Utility and Validity 
A study in 2010 by Bruyere et al. (2010) using 353 patients undergoing prostate biopsy show that the routine use of obtaining a pre-operative urine culture is not clinically relevant to positive outcomes. “Of the 353 men, 12 had a pre-biopsy-positive bacterial culture and underwent prostate biopsy without any infectious complication. Fifteen patients with a negative pre-biopsy culture developed a post-biopsy-positive bacterial culture, but remained asymptomatic without any treatment. Only four men from the group without pre-biopsy bacteriuria developed an infectious complication, requiring 3 weeks of antibiotic therapy.” Both experimental and control groups had similar rates of complication, suggesting “that routine urine bacterial culture before prostate biopsy is not useful when antibiotic prophylaxis and enema are performed” (Bruyere et al., 2010).

The method of obtaining the urine sample for culture testing is important. This is especially true for children. A 2017 study of 4808 acutely ill children demonstrated that there was modest agreement between the results obtained if the test was conducted by a research laboratory versus a health service laboratory; however, the method of obtaining the urine sample did have significance. The calculated areas under the receiver-operator curve (AUC) for UTI ranged from 0.75 – 0.86 if the sample was obtained using a clean-catch method versus AUC values of 0.65 – 0.79 if the sample was obtained using “nappy pad samples”. The authors conclusions were that urine cultures did not necessarily have to be sent to a research lab for testing, but that “primary care clinicians should try to obtain clean catch samples, even in very young children” (Birnie et al., 2017). A smaller study of 83 infants compared the use of urine obtained either via bladder catheterization or suprapubic aspiration (SPA) (Eliacik et al., 2016). All 83 infants had previously tested positive using urine culture samples obtained via bladder catheterization. Then, they had samples removed by SPA. The SPA samples were used in both urinalysis and urine culture testing, and “only 24 (28.9%) and 20 (24%) yielded positive urine culture and abnormal urinalysis data, respectively.” This indicates a 71.1% false positive result rate if the urine sample is obtained using bladder catheterization. “In infants younger than 12 months, SPA is the best method to avoid bacterial contamination, showing better results than transurethral catheterization” (Eliacik et al., 2016).

Another study by Ducharme et al. (2007) researched the use of either urine cultures and/or reagent test strips for use in diagnosing UTIs in elderly patients. The study consisted of 100 elderly patients with one group having no symptoms and non-infectious complaints and a second group “presenting with acute confusion, weakness or fever but no apparent urinary symptoms”. Their results show that “of the 33 positive cultures, 10 had negative reagent strips. Thirteen of the 14 positive nitrite tests were culture positive for a specificity of 92.8% and a sensitivity of 36.1%. Positive cultures did not infer a diagnosis of UTI. Of the 67 positive reagent strips, 41 (61.2%) were associated with negative cultures.” They conclude that, “in the elderly, reagent testing is an unreliable method of identifying patients with positive blood cultures. Moreover, positive urine culture rates are only slightly higher in patients with vague symptoms attributable to UTI than they are in (asymptomatic) patients treated for non-urologic problems, which suggests that many positive cultures in elderly patients with non-focal systemic symptoms are false-positive tests reflecting asymptomatic bacteriuria and not UTIs” (Ducharme et al., 2007).

A study by Price et al. (2016) show that using an enhanced quantitative urine culture (EQUC) increased the detection of microorganisms in UTIs. This study consisted of 150 female patients using an initial UTI symptom assessment questionnaire to divide them into symptomatic and asymptomatic groups. Both sets underwent culture testing using both conventional urine culture testing and an EQUC method. “Compared to expanded-spectrum EQUC, standard urine culture missed 67% of uropathogens overall and 50% in participants with severe urinary symptoms. Thirty-six percent of participants with missed uropathogens reported no symptom resolution after treatment by standard urine culture results.” Their protocol resulted in an “84% uropathogen detection relative to 33% detection by standard urine culture” (Price et al., 2016). 

Cantey et al. (2015) evaluated the utility of a Gram stain relative to UA. In reviewing 312 pediatric patients with suspected UTIs who had urine cultures, UA, and Gram stain performed, the researchers concluded that the UA “has excellent negative predictive value that is not enhanced by urine Gram stain and that antibiotic selection did not vary based on the urine Gram stain result.” When compared to the urine Gram stain, the UA had equal sensitivity (97.3% vs 97.5%) and a higher specificity (85% vs 74%). This could allow the UA to take precedent as a test performed over the Gram stain due to its increased efficiency and lower cost (Cantey et al., 2015). 

Petty et al. (2019) evaluated the risk factors and clinical outcomes of treating asymptomatic bacteriuria (ASB) in hospitalized patients. There were 2733 patients with ASB (defined as “positive urine culture without any documented signs or symptoms attributable to urinary tract infection”) included in the study. A total of 2259 patients were treated with antibiotics for an average of seven days. Certain characteristics tended to correlate with ASB treatment, such as positive urinalysis (odds ratio [OR] = 2.83), leukocytosis (OR = 1.55), and dementia (OR = 1.57). However, treatment of ASB was found to be associated with longer duration of hospitalization after urine testing (four vs three days; relative risk, 1.37), although no other differences in secondary outcomes were identified. The authors concluded that “hospitalized patients with ASB commonly receive inappropriate antibiotic therapy. Antibiotic treatment did not appear to be associated with improved outcomes; rather, treatment may be associated with longer duration of hospitalization after urine testing.” The authors also recommended stewardship efforts to reduce inappropriate treatment (Petty et al., 2019).

Coussement et al. (2019) investigated the prevalence of ASB among kidney transplant patients beyond two months post-transplant. The authors identified 500 post-transplant patients, of which 17 had ASB (3.4%). Further, of the 76 patients that were 2 – 12 months post-transplant, only one had ASB, and of the other 424 patients, 16 patients had ASB. The authors concluded that the prevalence of ASB past the second month of kidney transplant was low and that further studies were needed to ascertain the cost-effectiveness of the screen-and-treat strategy in this population (Coussement et al., 2019). This finding regarding screening and treating ASB was confirmed by Fontserè et al. (2021), who found that the “treatment of A[S]B diminished the microbiological cure and increased the rates of microbiologic relapses and reinfections … treated A[S]B patients showed a trend of developing symptomatic urinary tract infection in the following six months.” 

Choosing Wisely 
Choosing Wisely, an initiative by the American Board of Internal Medicine (ABIM) Foundation, consists of several national organizations representing medical specialists that write recommendations within their respective field to help choose care based on scientific evidence and to help reduce testing redundancy.

2019 AMDA-The Society for Post-Acute and Long-Term Care Medicine (AMDA) 
In 2019 and 2022, the AMDA updated their earlier 2017 Choosing Wisely guideline concerning the use of urine cultures. Due to over-use of antibiotics and overtreatment of UTIs, they state “Don’t obtain urine tests until clinical criteria are met.” Since the urine culture would have a high likelihood of yielding a positive result in an otherwise asymptomatic case, this “contributes to the over-use of antibiotic therapy in this setting, leading to an increased risk of diarrhea or other adverse drug events, resistant organisms and infection due to Clostridioides difficile.” They also note that “the finding of asymptomatic bacteriuria may lead to an erroneous assumption that a UTI is the cause of an acute change of status, hence failing to detect or delaying the timelier detection of 5 signs and symptoms likely indicative of uncomplicated cystitis. These include dysuria, and one or more of the following: frequency, urgency, supra-pubic pain or gross hematuria” (AMDA, 2022). 

2018 American Academy of Pediatrics-Section on Nephrology (ASPN) and the American Society of Pediatric Nephrology (AAP) 
The AAP Section on Nephrology and the ASPN issued a joint Choosing Wisely recommendation stating, “Avoid ordering follow-up urine cultures after treatment for an uncomplicated urinary tract infection (UTI) in patients that show evidence of clinical resolution of infection. Studies have shown that clinical resolution of infection is adequate for determining effectiveness of antibiotic therapy after treatment for a UTI” (AAP & ASPN, 2018).

2016 American Academy of Pediatrics (AAP) 
The AAP updated their Choosing Wisely recommendation in 2022: “Avoid the use of surveillance cultures for the screening and treatment of asymptomatic bacteriuria. There is no evidence that surveillance urine cultures or treatment of asymptomatic bacteriuria is beneficial. Surveillance cultures are costly and produce both false positive and false negative results. Treatment of asymptomatic bacteriuria is harmful and increases exposure to antibiotics, which is a risk factor for subsequent infections with a resistant organism. This also results in the overall use of antibiotics in the community and may lead to unnecessary imaging” (AAP, 2016).

2019 Society for Healthcare Epidemiology of America (SHEA) 
The SHEA recommendation in Choosing Wisely is more encompassing: “Don’t perform cultures (e.g. urine, blood, sputum cultures) or test for C. difficile unless patients have signs or symptoms of infection. Tests can be falsely positive leading to over diagnosis and overtreatment. Although important for diagnosing disease when used in patients with appropriate signs or symptoms, these tests often are positive when an infection is not present. For example, in the absence of signs or symptoms, a positive blood culture may represent contamination, a positive urine culture could represent asymptomatic bacteriuria, and a positive test for C. difficile could reflect colonization. There are no perfect tests for these or most infections. If these tests are used in patients with low likelihood of infection, they will result in more false positive tests than true positive results, which will lead to treating patients without infection and exposing them to risks of antibiotics without benefits of treating an infection” (SHEA, 2019). 

European Association of Urology (EAU) 
The EAU has guidelines for urological infections that are updated annually. With respect to ASB, they state (all with a ‘Strong’ strength of rating), “Do not screen or treat asymptomatic bacteriuria in the following conditions:

• Individuals without risk factors;
• Patients with well-regulated diabetes mellitus;
• Post-menopausal [individuals];
• Elderly institutionalised patients;
• Patients with dysfunctional and/or reconstructed lower urinary tracts;
• Patients with renal transplants;
• Patients prior to arthroplasty surgeries;
• Patients with recurrent urinary tract infections.”

They do recommend with a ‘Strong’ rating to “screen for and treat asymptomatic bacteriuria prior to urological procedures breaching the mucosa” and a ‘Weak’ rating to “screen for and treat asymptomatic bacteriuria in pregnant [individuals] with standard short course treatment or single dose fosfomycin trometamol.” They do recommend to “diagnose recurrent UTI by urine culture” with a ‘Strong’ rating. Please note that recurrent UTI indicates that the occurrences are symptomatic. It is further specified that “A urine culture must therefore be taken prior to such interventions”. 

With respect to uncomplicated cystitis, they give a ‘Strong’ rating to only perform urine culture analysis “in the following situations:

• Suspected acute pyelonephritis;
• Symptoms that do not resolve or recur within four weeks after the completion of treatment;
• Individuals who present with atypical symptoms;
• Pregnant [individuals].”

The EAU gives a ‘Weak’ recommendation to “use urine dipstick testing for diagnosis of acute uncomplicated cystitis.”

In cases of uncomplicated pyelonephritis, the EAU recommends with a ‘Strong’ rating to “perform urinalysis (e.g., using the dipstick method), including the assessment of white and red blood cells and nitrite, for routine diagnosis” and to “perform urine culture and antimicrobial susceptibility testing in patients with pyelonephritis.”

The EAU defines complicated UTI (cUTI) as occurring “in an individual in whom factors related to the host (e.g., underlying diabetes or immunosuppression) or specific anatomical or functional abnormalities related to the urinary tract (e.g. obstruction, incomplete voiding due to detrusor muscle dysfunction) are believed to result in an infection that will be more difficult to eradicate than an uncomplicated infection.” Other factors associated with cUTIs include vesicoureteral reflux, recent history of instrumentation, UTI in males, pregnancy, and healthcare-associated infections. “Laboratory urine culture is the recommended method to determine the presence or absence of clinically significant bacteriuria in patients suspected of having a cUTI”.

For catheter-associated UTIs (CAUTI), the EAU recommends with ‘Strong’ ratings to “not carry out routine urine culture in asymptomatic catheterised patients,” to “not use pyuria as sole indicator for catheter-associated UTI,” and to “not use the presence or absence of odorous or cloudy urine alone to differentiate catheter-associated asymptomatic bacteriuria from catheter-associated UTI.”

In cases of urethritis, the EAU states that “Clinicians should always perform point-of-care diagnostics (e.g. Gram staining, first-void urine with microscopy, leukocyte esterase testing) if available to obtain objective evidence of urethral inflammation and to guide treatment … men who meet the criteria for urethritis should be tested for C. trachomatis, M. genitalium and N. gonorrhoeae with nucleic acid amplification tests (NAAT), even if point-of-care tests are negative for gonorrhoeae … N. gonorrhoeae and chlamydia cultures are mainly to evaluate treatment failures and monitor developing resistance to current treatment.” With a ‘Strong’ rating, they recommend:

• “Perform a Gram stain of urethral discharge or a urethral smear to preliminarily diagnose gonococcal urethritis.”
• “Perform a validated nucleic acid amplification tests on a first-void urine sample or urethral smear to prior to empirical treatment to diagnose chlamydial and gonococcal infections.”
• “Perform a urethral swab culture, prior to initiation of treatment, in patients with a positive NAAT for gonorrhoea to assess the antimicrobial resistance profile of the infective strain.”
• “Use a pathogen directed treatment based on local resistance data.”

For urosepsis, the EAU strongly recommends to “Take a urine culture and two sets of blood cultures before starting antimicrobial treatment.”

For the diagnosis and disease management of bacterial prostatitis (BP), the EAU recommends with a ‘Strong’ rating to “perform the Meares and Stamey 2- or 4-glass test in patients with [chronic bacterial prostatitis (CBP)]”. They only give a ‘Weak’ rating in the use of the urine dipstick test and blood culture with a total blood count for acute bacterial prostatitis (ABP). They also give a ‘Weak’ rating to their recommendation to “not routinely perform microbiological analysis of the ejaculate alone to diagnose CBP”; however, they give a ‘Strong’ recommendation to “treat acute bacterial prostatitis according to the recommendations for complicated UTIs” where they recommend a laboratory urine culture. 

The EAU’s recommendation in cases of suspected acute infective epididymitis (with a ‘Strong’ rating) is “to obtain a mid-stream urine and a first-voided urine for pathogen identification by culture and nucleic acid amplification test.” It should be noted that, if the acute scrotal pain and/or swelling is due to suspected torsion, then a urine culture is not necessary. In that case, “urgent surgical exploration” is recommended instead (Bonkat et al., 2024).