Urinary tract infections (UTIs) are the most common human infections. But urine culture, the cornerstone for laboratory diagnosis of UTI, is imperfect. It has a high frequency of false results, both positive and negative.
Urine culture takes 2 to 3 days to return the result, and antibiotics are often indicated empirically, pending final culture readings. On the other hand, asymptomatic bacteriuria - the presence of bacteria in the urine in the absence of UTI symptoms - generally does not warrant treatment.
Current consensus-based guidance recommends performing appropriate urinalysis and interpreting the results for the possibility of a UTI. The guideline (Claeys et al), describes approaches to reducing unnecessary laboratory antibiotics and misdiagnosis of UTI, and is organized according to the procedure for urine culture, ordering, processing and reporting.
The authors developed a guideline based on the modified Delphi approach to determine best practices for urine culture-related diagnoses. The most important principles of the guideline avoid testing and treatment of asymptomatic bacteriuria, and also avoid the use of fluoroquinolones for the first-line treatment of acute cystitis. These principles are corroborated by other important guides.
| Clinical setting |
The guideline relates to the diagnostic interpretation of urine culture in outpatients and inpatients, and specifically addresses long-term care, inpatient, outpatient, and emergency department practice settings.
| Intended goal |
This review is intended for doctors who diagnose and treat UTIs, and for those who perform or report urine studies.
| Who wrote the guides? |
The guide includes 18 general statements written by a panel of experts chosen from various geographic regions.
The panel included 15 individuals with specialization in health epidemiology and quality improvement, medical informatics and decision support, infectious diseases, clinical microbiology, antimicrobial stewardship and urology, and with experience in the management of UTI, studies diagnostics, clinical microbiology and infection prevention.
Thirteen of the 15 panelists were doctors and 10 of them were infectious disease specialists. Clinical pathologists trained and board certified in the general practice of laboratory medicine did not participate in the panel.
The modified Delphi approach using the RAND/UCLA Appropriateness Method was used to determine best practices in urine culture-related diagnosis.
The expert panel rated their recommendations on a Likert scale, and subsequently met to further discuss points of disagreement. After a second review, the final set of guidance statements was developed.
| What are the main recommendations? |
The main recommendations focus on optimizing the diagnosis based on the results of urinalysis and urine culture, and the administration of antibiotics. Recommendations are broadly categorized into urine culture ordering, processing, and reporting, along with associated appropriate or inappropriate practice.
| Urine Culture Ordering, Processing, and Reporting: Key Points from the Expert Guide | |
| Scenery | Appropriate practices |
| Application | Require proper harvest documentation (e.g., clean catch) Only test patients with documented signs and symptoms of urinary tract infection. |
| Prosecution | Use a reflex culture protocol when possible, so that urine without inflammatory markers (i.e. white blood cells) is not cultured, as this helps prevent microbial characterization and inappropriate treatment of asymptomatic bacteriuria Do not routinely test any isolate when more than 2 types of bacteria are recovered per culture. |
| Report | Optimize lab reports: • Include a disclaimer that elevated colony counts may be present in asymptomatic bacteriuria • "Encourage" prescribers not to treat asymptomatic bacteriuria or mixed growth • Clearly define isolates identified as uropathogens or probable skin contaminants • Use antibiotic cascade reporting, which does not report fluoroquinolones as first-line antibiotics |
> Urine culture request
Appropriate practice for ordering a urine culture includes documenting signs or symptoms of UTI to obtain a urine culture, with the goal of replacing stand-alone urine culture orders with a “reflex culture” protocol (i.e., when urinalysis and urine culture are ordered together, the culture is performed only if the urinalysis criteria are met) based on the urinalysis results, and automatically cancel the repeat urine culture within 5 days of a positive culture, during the same hospital admission.
| Requesting Urine Cultures: Appropriate and Inappropriate Signs and Symptoms to Document | ||
| Urinary catheter status | Appropriate signs and symptoms | Inappropriate signs |
| Patient with urinary catheter | Dysuria, suprapubic pain, flank pain, costovertebral annulus tenderness, alternative septic shock. | Alternating mental status, characteristic urinary changes |
| Patient without urinary catheter | Dysuria, suprapubic pain, flank pain, angle pain or costovertebral septic shock | Characteristic urinary changes |
Inappropriate practice is including the culture along with standard requests (emergency department, hospitalization, preoperative, altered mental status, and falls evaluation), or ordering urine cultures in response to a change in urine characteristics.
> Processing of urine cultures
Appropriate practice includes the use of an elevated white blood cell count platform on urine microscopy, as a criterion for reflex culture, when a urine culture is ordered by a clinician. On the other hand, before processing the cultures, the method of urine collection must be documented (clean catch at midstream, indwelling catheter, straight inlet and outlet catheterization).
Inappropriate practice includes automatically obtaining reflex cultures based on urinalysis results in cases where a urine culture was not specifically requested.
> Urine culture report
Appropriate practice should include urine culture reports that inform physicians that counts of more than 100,000 colony-forming units (CFU)/ml may not represent a true infection in the absence of symptoms, and remind them not to treat patients with asymptomatic bacteriuria. or mixed flora.
On the other hand, the culture report must differentiate between typical uropathogens and contaminants. The identification and sensitivity of isolation tests should not be routinely reported when more than 2 unique bacterial isolates are found in the culture.
For example, the authors’ clinical reference laboratory provides the following comments along with culture results with growth of ≥3 organisms: Mixed microbiota , No further study. Mixed microbiota may be due to urinary contamination with bacteria from the skin at the time of collection or presence of a long-term urinary catheter . If a new culture is necessary, please consider re-educating the patient in the proper technique for collecting the midstream or performing the collection via direct catheterization.
An additional appropriate practice, called cascade reporting , is that antibiotics recommended by the Infectious Diseases Society of America (IDSA) should be reported preferentially if an organism is susceptible. Fluoroquinolone susceptibility testing should be discontinued unless there is resistance to the preferred oral antibiotics.
Inappropriate practice would include suggesting not to treat when <100,000 CFU/ml of bacteria are recovered, and withholding culture information and waiting for the prescriber to contact the clinical microbiology laboratory to release the results.
| How is it different from previous guidelines? |
The goal of the current guideline is different from the goal of the IDSA/American Society for Microbiology (ASM) guidelines in that the focus is on best implementation of urine testing for optimal treatment of UTIs. Its objective is to provide a systematized guide to influence the diagnostic process on a large scale.
The 2018 IDSA/ASM “Guideline for Using the Microbiology Laboratory for the Diagnosis of Infectious Diseases,” which includes the urine culture guide, does not disagree with any of the guidance offered by Claeys et al, but offers additional points.
The IDSA/ASM guideline states that if urine is transported at room temperature, it should be placed in boric acid preservative tubes (“gray cap”). An alternative is to refrigerate the urine after collection and during transport, or, if not refrigerated, it can be inoculated within 30 minutes of collection without preserving it with boric acid. The IDSA/ASM guideline also states that the use of a pyuria-based reflex culture protocol should be a locally approved policy.
The Claeys et al guidance does not address preanalytical considerations to prevent bacterial overgrowth during transport.
| What is the expected clinical impact? |
The clinical impact of the guideline can be stratified into 2 main categories: reduction of unnecessary antibiotic use and cost avoidance through decreased requests for urine cultures and inappropriate therapy.
> Reduction of excessive use of antibiotics
Exposure to antibiotics is a strong risk factor for antibiotic-resistant UTIs and other infections. Antibiotic use is associated with increased resistance at the population level. It is also associated with a higher risk of Clostridioides difficile colitis and vulvovaginal candidiasis, due to disruption of the healthy microbiome. Therefore, reducing unnecessary antibiotic use is a critical aspect to delay and minimize the emergence of resistance and reduce collateral pathology.
Claeys et al’s guidance provides actionable measures to reduce unnecessary antibiotic use during each stage of the urine culture process, i.e., ordering, processing, and reporting. Recommendations are provided for measures to avoid unnecessary detection and treatment of asymptomatic bacteriuria. In one study, almost 70% of patients with asymptomatic bacteriuria were treated with antibiotics, despite lack of benefit and discordance with existing guidelines.
The current recommendation is that the physician requesting a urine culture be asked to document the signs and symptoms of the infection. Assignment of a symptom complex to a culture is designed to reduce testing in the absence of UTI symptoms and therefore to subsequently reduce unnecessary treatment of asymptomatic bacteriuria.
An additional guideline designed to limit treatment of asymptomatic bacteriuria is the recommendation that culture reports remind or “prompt” clinicians not to treat asymptomatic bacteriuria and that even high colony counts (>100,000 CFU/ ml) may not represent a true infection in the absence of signs and symptoms.
Furthermore, the guideline provides a strategy to decrease the time and resources required to achieve a final laboratory result by screening with urinalysis before culture. A urine culture usually takes ≥2 days to return a result with interpretation of antibiotic sensitivity testing. However, if a reflex culture protocol is used as recommended by the guideline, the time to the final result is usually significantly reduced, and culture would be obviated. This practice could lead to a reduction in unnecessary antibiotic use.
> Cost reduction
It is estimated that around 27% of hospitalizations are associated with a urine culture. Urine cultures requested in other care settings (emergency, outpatient and long-term) must be added to this percentage. This underscores the opportunity to avoid costs associated with a reflex culture protocol. The additional cost savings would be associated with the reduction in the treatment of asymptomatic bacteriuria.
| Do other societies agree or disagree? |
The main principle of not treating asymptomatic bacteriuria described in the Claeys et al guideline is agreed upon by other major societies. IDSA, the American Society of Urology (AUA), and the European Association of Urology (EAU) agree that asymptomatic bacteriuria should generally not be treated outside the context of pregnancy or before a subset of urologic interventions.
The guideline is also corroborated by the Choosing Wisely health education campaign and the American Board of Internal Medicine , which recommends not performing urine cultures in the absence of symptoms and not treating asymptomatic bacteriuria. The IDSA/ASM guide recommends that a reflex cultivation policy be established at the local level.
Existing guidelines vary as to the limit for uropathogen growth in standard culture. For example, the CDC (US Centers for Disease Control and Prevention) requires at least 100,000 CFU/ml to meet its criteria for diagnosing a UTI. In contrast, the IDSA/ASM guidelines have a more flexible threshold and include growth <100,000 CFU/m.
> Fluoroquinolones
Similar to the Claeys et al guideline, the IDSA, AUA, and EAU guidelines emphasize that fluoroquinolones should be avoided in patients with uncomplicated cystitis. For example, the European Society for Microbiology and Infectious Diseases guideline highlights that fluoroquinolones are highly effective but are prone to significant side effects and should be reserved for uses other than acute cystitis, and be considered an alternative and not a regimen. first line.
The EAU guidelines state that fluoroquinolones should not be used to treat uncomplicated cystitis, and the AUA guidelines recommend taking into account that serious adverse effects associated with fluoroquinolones including tendonitis, tendon rupture, QT prolongation and C. difficile infection , which generally outweigh the benefits in uncomplicated UTI. It is noted that the IDSA, AUA, and EAU recommendations do not necessarily apply to patients with complicated UTI (e.g., aberrant anatomy, foreign body) or immunocompromise.
| How will this change daily practice ? |
Most of the statements in the Claeys et al guidance are generally accepted good practice. However, the guidance also adds weight to the increasingly common practice of using a reflex culture approach to preclude culturing urine samples in which there is no inflammation (i.e., no white blood cells). The guideline deemphasizes the traditional cutoff of 100,000 CFU/ml as a diagnostic criterion for UTI, which is consistent with IDSA’s previous emphasis of this cutoff.
The cutoff of 100,000 CFU/mL was developed based on a population with pyelonephritis and has since been shown to be inadequate. The current guidance reemphasizes generally accepted principles, namely that even cultures with growth of more than 100,000 CFU/mL do not require treatment in patients without symptoms, and that UTI may be associated with growth of <100,000 CFU/mL. mL of uropathogens.
The framework provided for the administration of fluoroquinolones may reduce the prescribing of this class of drugs. In 2016, the US Food and Drug Administration (FDA) added a boxed warning to fluoroquinolones due to their association with tendinitis and tendon rupture. However, there is evidence that the boxed warning has had little effect on fluoroquinolone prescribing patterns for uncomplicated UTI, and little effect on high rates of fluoroquinolone resistance.
The authors believe that one of the biggest impacts of the current guidance could be in reversing these trends in daily practice, encouraging laboratories to avoid routinely reporting fluoroquinolones as first-line antibiotics for UTI.
| Special Considerations: When would the guidance not apply? |
The Claeys et al guidance does not apply to a number of clinical scenarios. Children and pregnant women are excluded. Kidney transplant recipients and severely immunocompromised patients were specifically excluded. However, detection and treatment of asymptomatic bacteriuria is indicated in pregnancy, as the benefit of treatment may outweigh the risks.
> Considerations for patients with urological conditions
Detection and treatment of asymptomatic bacteriuria is indicated before urologic surgical procedures that involve manipulation of the upper urinary tract or cause mucosal trauma, while the benefits of treatment may outweigh the risks.
For patients with a urinary catheter or requiring intermittent catheterization, as well as for patients with neurogenic lower urinary tract dysfunction or intestinal interposition in the urinary tract (e.g., ileal conduit, neobladder), the usefulness of the culture approach reflex has not been established empirically. On the other hand, the IDSA guideline for catheter-associated UTI states that pyuria should not be used to differentiate between catheter-associated UTI and asymptomatic bacteriuria.
Symptoms of UTI in these patients can be subtle and variable and may include increased spasticity, autonomic dysreflexia, and feelings of malaise. Symptoms should be considered in the context of the physical examination and urine studies, especially because the urine of these patients is often chronically colonized by bacteria.
> Other patients under urological care
Complete urine culture profiles with antimicrobial sensitivity may be necessary in urological patients, regardless of urinalysis results. Such circumstances may include contexts before or after urological procedures, as well as suspected cases of prostatitis, epididymorrhitis, fistulas or recurrent UTI.
The clinical appropriateness of performing cultures for urology patients should be at the discretion of the treating urologist and independent cultures should not be reverted to reflex cultures in urology patients without prior discussion with the urology team. Likewise, a culture within 5 days of another culture should not be canceled in a urologic patient prior to a discussion with the team ordering the culture. Such culture may be necessary in the setting of refractory symptoms, to evaluate the possibility of recurrent infection or continued contamination.
In urological patients, species identification and antimicrobial susceptibility testing of all isolates cultured in urine may be necessary before endourological procedures, even in cases of more than 2 organisms, as polymicrobial interactions may play a role. role in urological infection, so this should be left to the discretion of the urology team.
In select cases of UTI, the use of fluoroquinolones is appropriate. For example, the EAU guideline states that fluoroquinolones are an effective oral regimen for uncomplicated pyelonephritis. On the other hand, fluoroquinolones often exhibit excellent penetration into the prostate and are therefore associated with significant benefit, particularly if prostatitis is suspected, or in patients with febrile or recurrent UTI with prostate involvement. Therefore, fluoroquinolone sensitivity should be reported in such cases.
> Other considerations
In daily practice, a balance must be achieved between the diagnostic process and clinical practicality. For example, the guidance places demands for additional physician requests, and there must be a method to quickly designate an exception to the laboratory processing the samples. A series of “hard stops” for when the doctor is making orders can lead to inappropriate care if such hard stops are not applicable, as in the exceptional circumstances discussed above.
In early urinary sepsis, a subgroup of patients may not be able to describe symptoms, but changes in behavior or mental status may be witnessed or reported. Even in the absence of a catheter, performing a urine culture with antimicrobial susceptibility testing should be based on clinical judgment. In some patients with catheters, UTI may present with fever without septic shock, particularly in those unable to communicate, and therefore urine culture should be processed at the clinician’s discretion.
Applicant. Recently, machine learning has been shown to improve antimicrobial stewardship. Specifically, the use of machine learning-generated antibiotic recommendations was associated with minimizing antimicrobial resistance. As these models mature and undergo additional validation, their integration into antimicrobial and diagnostic stewardship is poised to lead to further reductions in antibiotic overuse, antimicrobial resistance, and financial burden for patients and health systems.
