UTI Diagnosis: A Clinician’s Guide to Accurate and Timely Identification

Uncomplicated urinary tract infections (UTIs) represent a significant portion of bacterial infections encountered in daily clinical practice. These infections primarily affect the lower urinary tract, specifically the bladder and surrounding structures. Distinguishing themselves from complicated UTIs, uncomplicated cases arise in individuals who are otherwise healthy, lacking structural abnormalities in their urinary tract or significant underlying health conditions. While some uncomplicated UTIs may resolve without intervention, many individuals seek medical care to alleviate distressing symptoms and prevent potential complications. Therefore, a Uti Diagnosis that is both prompt and accurate is paramount for ensuring timely and appropriate patient management. Furthermore, effective preventative strategies play a crucial role in diminishing the overall burden of UTIs on healthcare resources. By thoroughly understanding the essential elements of uncomplicated UTIs, healthcare professionals are empowered to optimize patient care, leading to improved health outcomes. This article offers a detailed review of uncomplicated UTIs, covering clinical presentation, diagnostic approaches, and treatment strategies, while also highlighting the collaborative role of the interprofessional team in delivering comprehensive patient care.

Objectives:

• Implement effective screening protocols for patients presenting with UTI symptoms, risk factors, and relevant medical history to facilitate early uti diagnosis.
• Select and accurately interpret appropriate diagnostic tests to confidently confirm UTIs and guide informed treatment decisions.
• Apply evidence-based guidelines, treatment protocols, and preventative measures to achieve optimal patient outcomes in uncomplicated UTIs.
• Foster effective collaboration within the interprofessional healthcare team to guarantee holistic and coordinated care for individuals with uncomplicated UTIs.

Understanding Uncomplicated UTIs

An uncomplicated UTI is defined as a bacterial infection localized to the bladder and related structures in individuals without underlying complicating factors. These factors typically include structural abnormalities of the urinary tract, comorbidities such as diabetes mellitus, immunocompromised states, recent urologic surgery, or pregnancy. Uncomplicated UTI is often used interchangeably with terms like cystitis or lower urinary tract infection.

It is crucial to differentiate between true UTI and asymptomatic bacteriuria or pyuria. The mere presence of bacteria or white blood cells in the urine without accompanying symptoms does not constitute a UTI. Classic symptoms suggestive of a UTI include increased urinary frequency, urgency, discomfort in the suprapubic region, and dysuria (painful urination). While UTIs are highly prevalent in women, they are less common in circumcised males. In circumcised males, the occurrence of a UTI is generally categorized as a complicated UTI, warranting further investigation.[1]

Although spontaneous resolution can occur in many cases of uncomplicated UTIs, patients frequently seek medical attention for symptomatic relief. The primary goals of therapy are to alleviate symptoms and to prevent the infection from ascending to the kidneys, potentially leading to pyelonephritis. Pyelonephritis, an upper tract infection, can cause damage to delicate nephron structures and potentially contribute to long-term complications such as hypertension.[2][3][4]

The cornerstone of uti diagnosis relies on a combination of clinical history and urinalysis, often confirmed by urine culture. Proper urine sample collection is indispensable for accurate laboratory evaluation and culture results.

It is important to note that complicated urinary tract infections and recurrent UTIs are distinct entities and are discussed in separate resources.

Clinical Presentation: Recognizing UTI Symptoms

Recognizing the clinical presentation of uncomplicated UTIs is the first critical step in uti diagnosis. Patients typically present with a constellation of lower urinary tract symptoms. These hallmark symptoms include:

• Dysuria: Pain or burning sensation during urination is a cardinal symptom.
• Urinary Frequency: An increased need to urinate more often than usual, even when the bladder is not full.
• Urinary Urgency: A sudden, compelling urge to urinate that is difficult to defer.
• Suprapubic Pain or Discomfort: Pain or pressure in the lower abdomen, above the pubic bone.
• Hesitancy: Difficulty initiating the urine stream.
• Bladder Spasms: Involuntary contractions of the bladder muscles, causing discomfort.
• Hematuria: Blood in the urine, which may be visible (gross hematuria) or microscopic.

It is important to note that in uncomplicated UTIs, systemic symptoms are typically absent. Patients generally do not present with:

• Fever: Elevated body temperature.
• Chills: Shivering accompanied by a feeling of coldness.
• Nausea and Vomiting: Stomach upset and emesis.
• Flank Pain or Back Pain: Pain in the sides or back, which is more indicative of kidney involvement (pyelonephritis).[8]

However, certain patient populations may present with atypical symptoms. For example, patients with neurological conditions such as multiple sclerosis may experience an exacerbation of their neurological symptoms during a UTI.

Clinical symptoms, while suggestive, can sometimes overlap with other conditions, including more serious infections like pyelonephritis. Differentiating between an uncomplicated UTI and a renal infection or other serious conditions can be challenging based on symptoms alone. In cases of diagnostic uncertainty, a cautious approach is warranted, and aggressive treatment for potential upper urinary tract disease should be considered.

Obtaining a thorough patient history is crucial. Information regarding prior antibiotic use and previous UTIs is important for guiding diagnostic and treatment decisions.

Physical examination findings in uncomplicated UTIs are often unremarkable. However, suprapubic tenderness may be elicited in a minority of cases (10% to 20%). In patients with recurrent UTIs, unexplained incontinence, or suspected pelvic organ prolapse, a pelvic exam may be indicated to identify potential contributing factors.[8]

Ultimately, uti diagnosis is a synthesis of clinical signs and symptoms, urinalysis findings, and, when necessary, urine culture confirmation. It is critical to avoid relying solely on urinalysis or culture results, particularly in asymptomatic patients. If clinical signs and symptoms are absent, the condition is unlikely to be a true UTI.

Cloudy or odoriferous urine is frequently associated with UTIs and bacteriuria by patients. However, these findings alone are not diagnostic of a UTI requiring antibiotic treatment unless accompanied by other characteristic signs and symptoms.[26] In such cases, optimizing hydration and carefully reviewing dietary and medication factors that could contribute to altered urine appearance or odor are important initial steps.

Factors unrelated to infection that can alter urine cloudiness (turbidity) and odor include:

• Amorphous phosphates
• Dietary factors (asparagus, Brussels sprouts, fish, garlic, onions, spices, sulfur-containing foods)
• Hormonal fluctuations (e.g., pregnancy)
• Hydration status
• Liver failure
• Medications (sulfonylurea)
• Renal failure
• Sexually transmitted infections
• Trimethylaminuria
• Vaginal infections
• Vitamins
• Voiding dysfunction unrelated to infection

Special Patient Populations and Symptom Presentation in UTI Diagnosis:

• Older and/or Frail Patients: In elderly individuals, typical UTI symptoms may be less prominent. Changes in mental status or behavior, such as new-onset confusion, unexplained lethargy, disorganized speech, or altered perception, may be the primary presenting signs.[26][27] In this population, the most reliable indicators for uti diagnosis are a change in mental status, abnormal urinalysis (pyuria and bacteriuria), and dysuria.[26] Other possible symptoms may include nocturia, incontinence, or a generalized feeling of unwellness without specific urinary complaints.[28]
• Spinal Cord-Injured Patients: Individuals with spinal cord injuries and paralysis may present with a distinct constellation of symptoms:
  • Autonomic Dysreflexia: Characterized by severe hypertension and headache in patients with spinal cord injuries at or above the T-6 level.[29]
  • Chills
  • Cloudy, foul-smelling urine
  • Fever
  • Increased or new onset of spasticity
  • Unexplained fatigue
• Patients with Permanent Indwelling Foley Catheters or Suprapubic Tubes: In patients with chronic indwelling catheters, the signs and symptoms of UTI can be vague. Elevated leukocyte count and low-grade fever may be present. Pyuria and high urinary bacterial colony counts are common in catheterized patients, but these findings alone do not automatically indicate a UTI requiring treatment unless systemic signs or symptoms such as pain, spasms, hematuria, or other abnormal bladder activity are present.

The Crucial Role of Urinalysis in UTI Diagnosis

Urinalysis serves as the cornerstone laboratory test in the uti diagnosis process. A properly collected urine specimen is essential for accurate results.

Urine Specimen Collection Techniques for Accurate UTI Diagnosis:

• Patient Preparation: Patients should be instructed to wash their hands thoroughly before collecting a urine sample.
• Midstream Clean-Catch Specimen: This method is generally preferred for non-obese women and men who can follow instructions correctly. The patient should begin voiding into the toilet, then, midstream, collect the urine sample into a sterile container, and finally finish voiding into the toilet. This technique aims to flush out contaminants from the urethra.
• Challenges in Obese Women: Obese women may face challenges in obtaining a clean-catch specimen due to skin folds potentially contaminating the sample.
• Epithelial Cells as Indicators of Contamination: The presence of epithelial cells in the urinalysis suggests that the urine sample was contaminated by contact with the genital skin surface and may not be representative of bladder urine.
• Urethral Catheterization: If a clean-catch specimen with minimal epithelial cells cannot be obtained, urethral catheterization may be necessary. The risk of inducing a UTI in uninfected women from a single, straight urethral catheterization is low, approximately 1%.
• Specimen Collection in Men: Men should be instructed to wipe the glans penis, initiate the urine stream to cleanse the urethra, and then collect a midstream sample.
• Special Populations: In young children and patients with spinal cord injuries, suprapubic aspiration, a more invasive technique, may be required to obtain an appropriate urine specimen.
• Catheterized Patients: In patients with indwelling Foley catheters, the existing catheter should be replaced, and the urine specimen should be collected directly from the newly placed catheter. It is crucial never to obtain a urine sample for culture or urinalysis from a urinary drainage bag, as this will not provide a representative sample of bladder urine. If necessary, the new Foley catheter can be clamped for a short period to allow sufficient urine to accumulate for sample collection.
• Timely Processing or Refrigeration: Urine specimens should be transported to the laboratory promptly or refrigerated if immediate processing is not possible. Bacteria can proliferate at room temperature, leading to an overestimation of bacterial counts and potentially misleading results regarding infection severity.[30][31]

Urinalysis Components and Interpretation in UTI Diagnosis:

Visual inspection of urine alone is insufficient for uti diagnosis. Cloudy urine can be present even in the absence of infection, with turbidity potentially arising from protein or calcium phosphate debris. Conversely, grossly infected urine can sometimes appear crystal clear. Therefore, dipstick testing should be performed on all urine samples.

Dipstick Urinalysis: Point-of-care dipstick tests can be conveniently performed in the clinic or at the bedside. The most diagnostically informative dipstick parameters for UTI assessment are:

• pH: Urine pH can be measured, although it is less specific for UTI diagnosis compared to other parameters.
• Nitrites: The nitrite test is a highly specific dipstick test for UTI. Bacteria, particularly Enterobacteriaceae (common UTI pathogens like E. coli), can convert nitrates (normally present in urine) to nitrites. This conversion process requires a minimum of 4-6 hours of bacterial incubation in the urine. Therefore, first-morning urine specimens, which have been in the bladder overnight, are often recommended, especially for nitrite testing in males. The specificity of the nitrite test is excellent, exceeding 90%.[33][34] A positive nitrite test directly indicates the presence of bacteria in the urine, strongly suggesting a UTI in symptomatic patients. However, it is important to note that some bacteria, particularly those more commonly associated with complicated UTIs (e.g., Enterococcus, Pseudomonas, Acinetobacter), do not efficiently convert nitrates to nitrites, potentially leading to false-negative nitrite results. The sensitivity of the nitrite dipstick test ranges from 19% to 48%, while its specificity is high, 92% to 100%.[35]
• Leukocyte Esterase: Leukocyte esterase is an enzyme released by white blood cells (leukocytes). Its presence in urine indicates pyuria, which is often associated with UTI but can also be present in other inflammatory conditions.
• Blood (Hematuria): The presence of blood in the urine (hematuria) can be a helpful finding in uti diagnosis. Bacterial infections of the bladder’s transitional cell lining can frequently cause some degree of bleeding. Hematuria can aid in differentiating UTI from conditions like vaginitis and urethritis, which typically do not cause blood in the urine.

It’s crucial to remember that in patients with UTI symptoms, a negative dipstick result does not definitively rule out a UTI, but positive findings significantly increase the likelihood of infection.

Studies have evaluated the predictive values of nitrite, leukocyte esterase, and blood on dipstick tests for uti diagnosis. Urinary nitrites have been found to be more predictive than leukocyte esterase, which in turn is more predictive than hematuria. The combination of positive nitrites and leukocyte esterase demonstrates a high positive predictive value (PPV) of 85% and a 92% negative predictive value (NPV).[36] The combined presence of all three (nitrites, leukocyte esterase, and hematuria) further enhances diagnostic utility.[37] In addition to dipstick findings, clinical symptoms such as dysuria and new-onset nocturia/frequency also strengthen the likelihood of a UTI.

Many laboratories have automated protocols where the detection of nitrites or leukocyte esterase on dipstick testing automatically triggers a microscopic evaluation of the urine for bacteria, white blood cells (WBCs), and red blood cells (RBCs), and/or a urine culture.

Microscopic Urinalysis: Microscopic examination of the urine sediment provides further valuable information. In uninfected urine, bacteria should not be visible. The presence of any bacteria observed on a Gram-stained urine specimen under high-power microscopy is strongly correlated with bacteriuria and UTI. An elevated WBC count in a properly collected urine sample, typically defined as >10 WBCs per high-power field (HPF), is considered abnormal and highly suggestive of a UTI in symptomatic patients.

Urine Culture: Confirmation and Guidance

Urine cultures are not routinely required for uti diagnosis in uncomplicated UTIs, especially in otherwise healthy women with typical symptoms. However, due to increasing antibiotic resistance and to differentiate between recurrent and relapsing infections, some guidelines recommend cultures more liberally.[8] Urine cultures are also essential when initial empiric antibiotic therapy fails, to guide subsequent treatment decisions.

Indications for Urine Culture in UTI Diagnosis:

Urine culture is recommended in the following situations:

• All men with suspected UTI: Due to the lower prevalence of uncomplicated UTIs in men and the higher likelihood of underlying complicating factors.
• Patients with diabetes mellitus: Diabetes increases the risk of complicated UTIs and antibiotic resistance.
• Immunocompromised individuals: These patients are at higher risk for severe infections and may require tailored antibiotic therapy.
• Pregnant women: Asymptomatic bacteriuria and UTIs in pregnancy require treatment to prevent complications.
• Recurrent UTIs: To identify the causative organism and resistance patterns in recurrent infections.
• Suspected pyelonephritis or complicated UTI: To guide antibiotic selection for more severe infections.
• Patients who do not improve with initial empiric antibiotic therapy: Culture results can guide targeted antibiotic therapy in treatment failures.

Interpreting Urine Culture Results for UTI Diagnosis:

Traditionally, the diagnostic threshold for a UTI based on urine culture has been >100,000 colony-forming units per milliliter (CFU/mL). However, more recent literature and guidelines, including the American Urological Association Core Curriculum, recognize that a lower threshold is clinically relevant in symptomatic patients. A urine culture showing >1,000 CFU/mL of a single uropathogenic organism in a symptomatic patient is now generally considered diagnostic for a UTI.[5] [38] It’s important to note that 20% to 40% of women with symptomatic UTIs may have ≤10,000 CFU/mL on urine culture.[5][38] Therefore, clinical correlation with symptoms is crucial when interpreting culture results, especially when colony counts are below the historical 100,000 CFU/mL threshold.

While urine cultures may not be routinely necessary in the emergency department setting, except perhaps in cases of recurrent UTIs, they can prove invaluable in guiding subsequent treatment if patients fail to respond to the initial antibiotic prescribed.[39] For a single, uncomplicated UTI, a culture may not always be mandatory; however, in cases of treatment failure, the clinician lacks objective evidence to guide further therapy without culture data. Consequently, many experts recommend obtaining a urine culture in all patients being treated for a presumed UTI, recognizing its potential value in various clinical scenarios.[8]

Role of Cystoscopy and Imaging in UTI Diagnosis:

Cystoscopy and urinary tract imaging are generally not indicated for uti diagnosis in uncomplicated UTIs, as they are rarely helpful in these cases.[39] Imaging studies may be considered in cases of relapsing infections to investigate potential underlying structural abnormalities or persistent sources of infection, but these are beyond the scope of uncomplicated UTI diagnosis.

Differential Diagnosis: Ruling Out Other Conditions

In the process of uti diagnosis, it is essential to consider and differentiate uncomplicated UTIs from other conditions that can mimic UTI symptoms. The differential diagnosis includes:

• Bladder stones: Can cause irritative voiding symptoms and hematuria.
• Complicated UTI: UTIs associated with structural abnormalities, comorbidities, or catheterization.
• Food or dietary issues: Certain foods can irritate the bladder or alter urine odor and appearance.
• Herpes simplex: Genital herpes can cause dysuria and urinary symptoms.
• Medication effects: Certain medications can cause urinary frequency or urgency as side effects.
• Overactive bladder (OAB): OAB syndrome presents with urinary urgency, frequency, and nocturia, but without infection.
• Pelvic inflammatory disease (PID): Infection of the female reproductive organs, can cause pelvic pain and urinary symptoms.
• Prostatitis: Inflammation of the prostate gland in men, can cause dysuria, frequency, and pelvic pain.
• Pyelonephritis: Kidney infection, presents with systemic symptoms (fever, chills, flank pain) in addition to urinary symptoms.
• Recurrent UTI: Repeated episodes of UTI, requires evaluation for underlying risk factors.
• Relapsing UTI: UTI recurrence with the same infecting organism, suggests persistent source of infection.
• Renal infarction: Blockage of blood supply to the kidney, can cause flank pain and hematuria.
• Renal stones: Kidney stones can cause flank pain, hematuria, and irritative voiding symptoms.
• Sexually transmitted infections (STIs): Chlamydia, gonorrhea, and trichomoniasis can cause urethritis and dysuria.
• Urethritis: Inflammation of the urethra, often caused by STIs or irritants, presenting with dysuria and discharge.
• Vaginitis: Inflammation of the vagina, can cause vaginal discharge, itching, and dysuria (external).

A careful history, physical examination, and appropriate laboratory tests are essential to differentiate uncomplicated UTIs from these other conditions and ensure accurate uti diagnosis.

Treatment and Management Strategies (Briefly touch upon, focus on diagnosis implication)

While the focus of this article is uti diagnosis, it’s important to briefly touch upon treatment and management, as accurate diagnosis directly informs appropriate therapy.

Antibiotic Therapy: Antibiotics are the mainstay of treatment for uncomplicated UTIs. First-line antibiotic agents commonly recommended include:

• Nitrofurantoin
• Trimethoprim-sulfamethoxazole (TMP/SMX)
• Fosfomycin
• First-generation cephalosporins

The choice of antibiotic should be guided by local antibiotic resistance patterns. If local E. coli resistance rates to a particular antibiotic exceed 20% or institution-specific guidelines, alternative agents should be considered. Historically, treatment durations varied from 3 days to 6 weeks; however, short-course therapy (3 days) is often effective for uncomplicated cystitis in women.

Importance of Antibiotic Stewardship: Overuse and misuse of antibiotics contribute to increasing antibiotic resistance. Accurate uti diagnosis is crucial to ensure that antibiotics are used appropriately, only when indicated, and with the most effective and narrow-spectrum agent possible. Asymptomatic bacteriuria, for example, generally does not require antibiotic treatment in non-pregnant adults, highlighting the importance of symptom-based diagnosis to avoid unnecessary antibiotic exposure.

Non-Antibiotic Management Strategies: In addition to antibiotics, adjunctive measures can help alleviate UTI symptoms. Increased fluid intake is generally recommended. For recurrent UTIs, preventative strategies beyond antibiotics may include optimizing personal hygiene, considering cranberry products, D-mannose, or methenamine.

Implication of Accurate Diagnosis for Treatment: A precise uti diagnosis is fundamental for selecting the most appropriate treatment strategy. It ensures that patients receive necessary antibiotic therapy when indicated, minimizing symptom duration and preventing complications. Conversely, accurate diagnosis also prevents unnecessary antibiotic use in conditions mimicking UTIs or in cases of asymptomatic bacteriuria, contributing to antibiotic stewardship and reducing the risk of resistance development.

Enhancing Healthcare Team Outcomes in UTI Diagnosis and Management

Effective management of UTIs, including accurate uti diagnosis, is best achieved through a collaborative interprofessional approach. Patient education is paramount in preventing recurrences, and nurses play a crucial role in this aspect. Primary care clinicians should consider referral to urology specialists for patients with relapsing or recurrent UTIs who do not respond to initial management strategies.

Clinicians should collaborate closely with pharmacists and/or infectious disease specialists to optimize antibiotic selection for UTI treatment. Familiarity with local bacterial resistance patterns is essential for informed antibiotic choices. Pharmacists can ensure appropriate antibiotic coverage, dosing, and duration, promoting patient safety and community well-being through optimal antibiotic stewardship. Nurses monitor patient progress, provide counseling on medication adherence, address patient inquiries, and communicate relevant observations or concerns to the clinical team.

All members of the healthcare team should actively monitor the patient’s clinical course. Identification of therapeutic failure or adverse drug events requires prompt communication and collaboration among team members to implement corrective actions. Early and accurate uti diagnosis and subsequent management lead to better patient outcomes. Optimal interprofessional team collaboration significantly enhances patient care in UTI management.[71][72]

Conclusion: Key Takeaways for UTI Diagnosis

Accurate and timely uti diagnosis is crucial for effective management of uncomplicated urinary tract infections and for promoting antibiotic stewardship. Key steps in achieving optimal uti diagnosis include:

• Thorough Symptom Assessment: Carefully evaluate patient-reported symptoms, recognizing typical and atypical presentations, particularly in vulnerable populations like the elderly and spinal cord-injured patients.
• Strategic Urinalysis: Utilize urinalysis, including both dipstick testing and microscopic examination, as the primary diagnostic tool. Interpret dipstick results (nitrites, leukocyte esterase, hematuria) in the context of clinical symptoms. Ensure proper urine specimen collection techniques to minimize contamination.
• Selective Urine Culture: Employ urine culture judiciously, reserving it for cases where clinically indicated, such as in men, pregnant women, immunocompromised individuals, recurrent infections, treatment failures, and suspected complicated UTIs or pyelonephritis. Interpret culture results considering current diagnostic thresholds (>1,000 CFU/mL in symptomatic patients).
• Differential Diagnosis Consideration: Maintain a broad differential diagnosis and consider other conditions that can mimic UTI symptoms, especially when clinical presentation is atypical or urinalysis findings are discordant with clinical suspicion.
• Interprofessional Collaboration: Foster effective communication and collaboration within the healthcare team to ensure comprehensive patient care, optimize antibiotic selection, and promote patient education.

By adhering to these principles of uti diagnosis, healthcare professionals can enhance the accuracy and timeliness of UTI identification, leading to improved patient outcomes, reduced antibiotic overuse, and better overall management of this common clinical condition.

References

1.Sabih A, Leslie SW. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Nov 12, 2023. Complicated Urinary Tract Infections. [PubMed: 28613784]
2.Five-day nitrofurantoin is better than single-dose fosfomycin at resolving UTI symptoms. Drug Ther Bull. 2018 Nov;56(11):131. [PubMed: 30297448]
3.Long B, Koyfman A. The Emergency Department Diagnosis and Management of Urinary Tract Infection. Emerg Med Clin North Am. 2018 Nov;36(4):685-710. [PubMed: 30296999]
4.Tang M, Quanstrom K, Jin C, Suskind AM. Recurrent Urinary Tract Infections are Associated With Frailty in Older Adults. Urology. 2019 Jan;123:24-27. [PMC free article: PMC8528015] [PubMed: 30296501]
5.Aggarwal N, Leslie SW, Lotfollahzadeh S. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): May 2, 2024. Recurrent Urinary Tract Infections. [PMC free article: PMC557479] [PubMed: 32491411]
6.Behzadi P, Behzadi E, Yazdanbod H, Aghapour R, Akbari Cheshmeh M, Salehian Omran D. A survey on urinary tract infections associated with the three most common uropathogenic bacteria. Maedica (Bucur). 2010 Apr;5(2):111-5. [PMC free article: PMC3150015] [PubMed: 21977133]
7.Yamaji R, Friedman CR, Rubin J, Suh J, Thys E, McDermott P, Hung-Fan M, Riley LW. A Population-Based Surveillance Study of Shared Genotypes of Escherichia coli Isolates from Retail Meat and Suspected Cases of Urinary Tract Infections. mSphere. 2018 Aug 15;3(4) [PMC free article: PMC6094058] [PubMed: 30111626]
8.Li R, Leslie SW. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): May 30, 2023. Cystitis. [PubMed: 29494042]
9.Leung AKC, Wong AHC, Leung AAM, Hon KL. Urinary Tract Infection in Children. Recent Pat Inflamm Allergy Drug Discov. 2019;13(1):2-18. [PMC free article: PMC6751349] [PubMed: 30592257]
10.May M, Schostak M, Lebentrau S., MR2- study group. Guidelines for patients with acute uncomplicated cystitis may not be a paper tiger: a call for its implementation in clinical routine. Int Urogynecol J. 2019 Feb;30(2):335-336. [PubMed: 30564871]
11.Lala V, Leslie SW, Minter DA. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jul 10, 2023. Acute Cystitis. [PubMed: 29083726]
12.Sakamoto S, Miyazawa K, Yasui T, Iguchi T, Fujita M, Nishimatsu H, Masaki T, Hasegawa T, Hibi H, Arakawa T, Ando R, Kato Y, Ishito N, Yamaguchi S, Takazawa R, Tsujihata M, Taguchi M, Akakura K, Hata A, Ichikawa T. Chronological changes in epidemiological characteristics of lower urinary tract urolithiasis in Japan. Int J Urol. 2019 Jan;26(1):96-101. [PubMed: 30308705]
13.Alperin M, Burnett L, Lukacz E, Brubaker L. The mysteries of menopause and urogynecologic health: clinical and scientific gaps. Menopause. 2019 Jan;26(1):103-111. [PMC free article: PMC6376984] [PubMed: 30300297]
14.Maharjan G, Khadka P, Siddhi Shilpakar G, Chapagain G, Dhungana GR. Catheter-Associated Urinary Tract Infection and Obstinate Biofilm Producers. Can J Infect Dis Med Microbiol. 2018;2018:7624857. [PMC free article: PMC6129315] [PubMed: 30224941]
15.Sobel JD. New aspects of pathogenesis of lower urinary tract infections. Urology. 1985 Nov;26(5 Suppl):11-6. [PubMed: 3904135]
16.Ipe DS, Horton E, Ulett GC. The Basics of Bacteriuria: Strategies of Microbes for Persistence in Urine. Front Cell Infect Microbiol. 2016;6:14. [PMC free article: PMC4744864] [PubMed: 26904513]
17.Chambers ST, Lever M. Betaines and urinary tract infections. Nephron. 1996;74(1):1-10. [PubMed: 8883013]
18.Kucheria R, Dasgupta P, Sacks SH, Khan MS, Sheerin NS. Urinary tract infections: new insights into a common problem. Postgrad Med J. 2005 Feb;81(952):83-6. [PMC free article: PMC1743204] [PubMed: 15701738]
19.Carlsson S, Wiklund NP, Engstrand L, Weitzberg E, Lundberg JO. Effects of pH, nitrite, and ascorbic acid on nonenzymatic nitric oxide generation and bacterial growth in urine. Nitric Oxide. 2001 Dec;5(6):580-6. [PubMed: 11730365]
20.Cornish J, Lecamwasam JP, Harrison G, Vanderwee MA, Miller TE. Host defence mechanisms in the bladder. II. Disruption of the layer of mucus. Br J Exp Pathol. 1988 Dec;69(6):759-70. [PMC free article: PMC2013295] [PubMed: 3064799]
21.Abraham SN, Miao Y. The nature of immune responses to urinary tract infections. Nat Rev Immunol. 2015 Oct;15(10):655-63. [PMC free article: PMC4926313] [PubMed: 26388331]
22.Mulvey MA, Lopez-Boado YS, Wilson CL, Roth R, Parks WC, Heuser J, Hultgren SJ. Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli. Science. 1998 Nov 20;282(5393):1494-7. [PubMed: 9822381]
23.Hudson PL, Hung KJ, Bergerat A, Mitchell C. Effect of Vaginal Lactobacillus Species on Escherichia coli Growth. Female Pelvic Med Reconstr Surg. 2020 Feb;26(2):146-151. [PubMed: 31990804]
24.Bunduki GK, Heinz E, Phiri VS, Noah P, Feasey N, Musaya J. Virulence factors and antimicrobial resistance of uropathogenic Escherichia coli (UPEC) isolated from urinary tract infections: a systematic review and meta-analysis. BMC Infect Dis. 2021 Aug 04;21(1):753. [PMC free article: PMC8336361] [PubMed: 34348646]
25.Paudel S, John PP, Poorbaghi SL, Randis TM, Kulkarni R. Systematic Review of Literature Examining Bacterial Urinary Tract Infections in Diabetes. J Diabetes Res. 2022;2022:3588297. [PMC free article: PMC9130015] [PubMed: 35620571]
26.Juthani-Mehta M, Quagliarello V, Perrelli E, Towle V, Van Ness PH, Tinetti M. Clinical features to identify urinary tract infection in nursing home residents: a cohort study. J Am Geriatr Soc. 2009 Jun;57(6):963-70. [PMC free article: PMC2692075] [PubMed: 19490243]
27.Juthani-Mehta M, Tinetti M, Perrelli E, Towle V, Van Ness PH, Quagliarello V. Interobserver variability in the assessment of clinical criteria for suspected urinary tract infection in nursing home residents. Infect Control Hosp Epidemiol. 2008 May;29(5):446-9. [PMC free article: PMC2671070] [PubMed: 18419369]
28.Mody L, Juthani-Mehta M. Urinary tract infections in older women: a clinical review. JAMA. 2014 Feb 26;311(8):844-54. [PMC free article: PMC4194886] [PubMed: 24570248]
29.Allen KJ, Leslie SW. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): May 30, 2023. Autonomic Dysreflexia. [PubMed: 29494041]
30.Richards KA, Cesario S, Best SL, Deeren SM, Bushman W, Safdar N. Reflex urine culture testing in an ambulatory urology clinic: Implications for antibiotic stewardship in urology. Int J Urol. 2019 Jan;26(1):69-74. [PubMed: 30221416]
31.Araujo da Silva AR, Marques AF, Biscaia di Biase C, Zingg W, Dramowski A, Sharland M. Interventions to prevent urinary catheter-associated infections in children and neonates: a systematic review. J Pediatr Urol. 2018 Dec;14(6):556.e1-556.e9. [PubMed: 30126746]
32.Karki N, Leslie SW. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): May 30, 2023. Struvite and Triple Phosphate Renal Calculi. [PubMed: 33760542]
33.Suresh J, Krishnamurthy S, Mandal J, Mondal N, Sivamurukan P. Diagnostic Accuracy of Point-of-care Nitrite and Leukocyte Esterase Dipstick Test for the Screening of Pediatric Urinary Tract Infections. Saudi J Kidney Dis Transpl. 2021 May-Jun;32(3):703-710. [PubMed: 35102912]
34.Chernaya A, Søborg C, Midttun M. Validity of the urinary dipstick test in the diagnosis of urinary tract infections in adults. Dan Med J. 2021 Dec 15;69(1) [PubMed: 34913433]
35.Malia L, Strumph K, Smith S, Brancato J, Johnson ST, Chicaiza H. Fast and Sensitive: Automated Point-of-Care Urine Dips. Pediatr Emerg Care. 2020 Oct;36(10):486-488. [PubMed: 29189595]
36.Bellazreg F, Abid M, Lasfar NB, Hattab Z, Hachfi W, Letaief A. Diagnostic value of dipstick test in adult symptomatic urinary tract infections: results of a cross-sectional Tunisian study. Pan Afr Med J. 2019;33:131. [PMC free article: PMC6754830] [PubMed: 31558930]
37.Little P, Turner S, Rumsby K, Warner G, Moore M, Lowes JA, Smith H, Hawke C, Turner D, Leydon GM, Arscott A, Mullee M. Dipsticks and diagnostic algorithms in urinary tract infection: development and validation, randomised trial, economic analysis, observational cohort and qualitative study. Health Technol Assess. 2009 Mar;13(19):iii-iv, ix-xi, 1-73. [PubMed: 19364448]
38.Wilson ML, Gaido L. Laboratory diagnosis of urinary tract infections in adult patients. Clin Infect Dis. 2004 Apr 15;38(8):1150-8. [PubMed: 15095222]
39.Anger J, Lee U, Ackerman AL, Chou R, Chughtai B, Clemens JQ, Hickling D, Kapoor A, Kenton KS, Kaufman MR, Rondanina MA, Stapleton A, Stothers L, Chai TC. Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline. J Urol. 2019 Aug;202(2):282-289. [PubMed: 31042112]
40.Gupta K. Emerging antibiotic resistance in urinary tract pathogens. Infect Dis Clin North Am. 2003 Jun;17(2):243-59. [PubMed: 12848469]
41.Raz R, Chazan B, Kennes Y, Colodner R, Rottensterich E, Dan M, Lavi I, Stamm W., Israeli Urinary Tract Infection Group. Empiric use of trimethoprim-sulfamethoxazole (TMP-SMX) in the treatment of women with uncomplicated urinary tract infections, in a geographical area with a high prevalence of TMP-SMX-resistant uropathogens. Clin Infect Dis. 2002 May 01;34(9):1165-9. [PubMed: 11941541]
42.Stein GE. Single-dose treatment of acute cystitis with fosfomycin tromethamine. Ann Pharmacother. 1998 Feb;32(2):215-9. [PubMed: 9496408]
43.Tutone M, Bjerklund Johansen TE, Cai T, Mushtaq S, Livermore DM. SUsceptibility and Resistance to Fosfomycin and other antimicrobial agents among pathogens causing lower urinary tract infections: findings of the SURF study. Int J Antimicrob Agents. 2022 May;59(5):106574. [PubMed: 35307561]
44.Kuzmenko AV, Kuzmenko VV, Gyaurgiev TA. [Efficiency of fosfomycin trometamol for treatment of acute uncomplicated cystitis]. Urologiia. 2018 Dec;(6):70-75. [PubMed: 30742381]
45.Jo JK, Kim DS, Sim Y, Ryu S, Kim KS. A Comparative Study of Urinary Tests and Cultures for the Effectiveness of Fosfomycin in Catheter-Related Urinary Tract Infections. J Clin Med. 2022 Dec 05;11(23) [PMC free article: PMC9736013] [PubMed: 36498803]
46.O’Grady MC, Barry L, Corcoran GD, Hooton C, Sleator RD, Lucey B. Empirical treatment of urinary tract infections: how rational are our guidelines? J Antimicrob Chemother. 2019 Jan 01;74(1):214-217. [PubMed: 30295780]
47.Ditkoff EL, Theofanides M, Aisen CM, Kowalik CG, Cohn JA, Sui W, Rutman M, Adam RA, Dmochowski RR, Cooper KL. Assessment of practices in screening and treating women with bacteriuria. Can J Urol. 2018 Oct;25(5):9486-9496. [PubMed: 30281006]
48.Ganzeboom KMJ, Uijen AA, Teunissen DTAM, Assendelft WJJ, Peters HJG, Hautvast JLA, Van Jaarsveld CHM. Urine cultures and antibiotics for urinary tract infections in Dutch general practice. Prim Health Care Res Dev. 2018 Aug 31;20:e41. [PMC free article: PMC6536752] [PubMed: 30168406]
49.Graninger W. Pivmecillinam–therapy of choice for lower urinary tract infection. Int J Antimicrob Agents. 2003 Oct;22 Suppl 2:73-8. [PubMed: 14527775]
50.Stair SL, Palmer CJ, Lee UJ. Evidence-based review of nonantibiotic urinary tract infection prevention strategies for women: a patient-centered approach. Curr Opin Urol. 2023 May 01;33(3):187-192. [PubMed: 36862100]
51.Konesan J, Liu L, Mansfield KJ. The Clinical Trial Outcomes of Cranberry, D-Mannose and NSAIDs in the Prevention or Management of Uncomplicated Urinary Tract Infections in Women: A Systematic Review. Pathogens. 2022 Dec 05;11(12) [PMC free article: PMC9788503] [PubMed: 36558804]
52.Bakhit M, Krzyzaniak N, Hilder J, Clark J, Scott AM, Mar CD. Use of methenamine hippurate to prevent urinary tract infections in community adult women: a systematic review and meta-analysis. Br J Gen Pract. 2021 Jul;71(708):e528-e537. [PMC free article: PMC8136580] [PubMed: 34001538]
53.Botros C, Lozo S, Iyer S, Warren A, Goldberg R, Tomezsko J, Sasso K, Sand P, Gafni-Kane A, Biener A, Botros-Brey S. Methenamine hippurate compared with trimethoprim for the prevention of recurrent urinary tract infections: a randomized clinical trial. Int Urogynecol J. 2022 Mar;33(3):571-580. [PubMed: 34115162]
54.Bartlett JE, De Bellis A. The prevention of urinary tract infections in aged care residents through the use of cranberry products: a critical analysis of the literature. Contemp Nurse. 2022 Aug;58(4):296-316. [PubMed: 35861109]
55.Jeitler M, Michalsen A, Schwiertz A, Kessler CS, Koppold-Liebscher D, Grasme J, Kandil FI, Steckhan N. Effects of a Supplement Containing a Cranberry Extract on Recurrent Urinary Tract Infections and Intestinal Microbiota: A Prospective, Uncontrolled Exploratory Study. J Integr Complement Med. 2022 May;28(5):399-406. [PMC free article: PMC9127832] [PubMed: 35285701]
56.Montorsi F, Gandaglia G, Salonia A, Briganti A, Mirone V. Effectiveness of a Combination of Cranberries, Lactobacillus rhamnosus, and Vitamin C for the Management of Recurrent Urinary Tract Infections in Women: Results of a Pilot Study. Eur Urol. 2016 Dec;70(6):912-915. [PubMed: 27283213]
57.Barea BM, Veeratterapillay R, Harding C. Nonantibiotic treatments for urinary cystitis: an update. Curr Opin Urol. 2020 Nov;30(6):845-852. [PubMed: 33009152]
58.Kranjčec B, Papeš D, Altarac S. D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World J Urol. 2014 Feb;32(1):79-84. [PubMed: 23633128]
59.Faustino M, Silva S, Costa EM, Pereira AM, Pereira JO, Oliveira AS, Ferreira CMH, Pereira CF, Durão J, Pintado ME, Carvalho AP. Effect of Mannan Oligosaccharides Extracts in Uropathogenic Escherichia coli Adhesion in Human Bladder Cells. Pathogens. 2023 Jun 28;12(7) [PMC free article: PMC10384913] [PubMed: 37513732]
60.Salvatore S, Ruffolo AF, Stabile G, Casiraghi A, Zito G, De Seta F. A Randomized Controlled Trial Comparing a New D-Mannose-based Dietary Supplement to Placebo for the Treatment of Uncomplicated Escherichia coli Urinary Tract Infections. Eur Urol Focus. 2023 Jul;9(4):654-659. [PubMed: 36621376]
61.Wagenlehner F, Lorenz H, Ewald O, Gerke P. Why d-Mannose May Be as Efficient as Antibiotics in the Treatment of Acute Uncomplicated Lower Urinary Tract Infections-Preliminary Considerations and Conclusions from a Non-Interventional Study. Antibiotics (Basel). 2022 Feb 25;11(3) [PMC free article: PMC8944421] [PubMed: 35326777]
62.Parazzini F, Ricci E, Fedele F, Chiaffarino F, Esposito G, Cipriani S. Systematic review of the effect of D-mannose with or without other drugs in the treatment of symptoms of urinary tract infections/cystitis (Review). Biomed Rep. 2022 Aug;17(2):69. [PMC free article: PMC9260159] [PubMed: 35815191]
63.Lenger SM, Chu CM, Ghetti C, Durkin MJ, Jennings Z, Wan F, Sutcliffe S, Lowder JL. d-Mannose for Recurrent Urinary Tract Infection Prevention in Postmenopausal Women Using Vaginal Estrogen: A Randomized Controlled Trial. Urogynecology (Phila). 2023 Mar 01;29(3):367-377. [PubMed: 36808931]
64.Ferrante KL, Wasenda EJ, Jung CE, Adams-Piper ER, Lukacz ES. Vaginal Estrogen for the Prevention of Recurrent Urinary Tract Infection in Postmenopausal Women: A Randomized Clinical Trial. Female Pelvic Med Reconstr Surg. 2021 Feb 01;27(2):112-117. [PubMed: 31232721]
65.Hooton TM, Vecchio M, Iroz A, Tack I, Dornic Q, Seksek I, Lotan Y. Effect of Increased Daily Water Intake in Premenopausal Women With Recurrent Urinary Tract Infections: A Randomized Clinical Trial. JAMA Intern Med. 2018 Nov 01;178(11):1509-1515. [PMC free article: PMC6584323] [PubMed: 30285042]
66.Albert X, Huertas I, Pereiró II, Sanfélix J, Gosalbes V, Perrota C. Antibiotics for preventing recurrent urinary tract infection in non-pregnant women. Cochrane Database Syst Rev. 2004;2004(3):CD001209. [PMC free article: PMC7032641] [PubMed: 15266443]
67.Smith AL, Brown J, Wyman JF, Berry A, Newman DK, Stapleton AE. Treatment and Prevention of Recurrent Lower Urinary Tract Infections in Women: A Rapid Review with Practice Recommendations. J Urol. 2018 Dec;200(6):1174-1191. [PubMed: 29940246]
68.Nicolle LE, Harding GK, Thomson M, Kennedy J, Urias B, Ronald AR. Efficacy of five years of continuous, low-dose trimethoprim-sulfamethoxazole prophylaxis for urinary tract infection. J Infect Dis. 1988 Jun;157(6):1239-42. [PubMed: 3259613]
69.Nicolle LE, Ronald AR. Recurrent urinary tract infection in adult women: diagnosis and treatment. Infect Dis Clin North Am. 1987 Dec;1(4):793-806. [PubMed: 3333659]
70.Liu Y, Xiao D, Shi XH. Urinary tract infection control in intensive care patients. Medicine (Baltimore). 2018 Sep;97(38):e12195. [PMC free article: PMC6160021] [PubMed: 30235665]
71.Li F, Song M, Xu L, Deng B, Zhu S, Li X. Risk factors for catheter-associated urinary tract infection among hospitalized patients: A systematic review and meta-analysis of observational studies. J Adv Nurs. 2019 Mar;75(3):517-527. [PubMed: 30259542]
72.Lengetti E, Kronk R, Ulmer KW, Wilf K, Murphy D, Rosanelli M, Taylor A. An innovative approach to educating nurses to clinical competence: A randomized controlled trial. Nurse Educ Pract. 2018 Nov;33:159-163. [PubMed: 30253916]
73.Vachhani AV, Barvaliya M, Naik V, Jha P, Tripathi C. Effectiveness and tolerability of short course co-trimoxazole, norfloxacin and levofloxacin in bacteriological cure of uncomplicated urinary tract infection in outpatient setting. An open label, parallel group, randomized controlled trial. Infez Med. 2015 Jun;23(2):155-60. [PubMed: 26110296]
74.Duane S, Beecher C, Vellinga A, Murphy AW, Cormican M, Smyth A, Healy P, Moore M, Little P, Devane D. A systematic review of the outcomes reported in the treatment of uncomplicated urinary tract infection clinical trials. JAC Antimicrob Resist. 2022 Apr;4(2):dlac025. [PMC free article: PMC8944192] [PubMed: 35350132]
75.Lodise TP, Henriksen AS, Hadley T, Patel N. US-Focused Conceptual Health Care Decision-Analytic Models Examining the Value of Pivmecillinam Relative to Current Standard-of-Care Agents Among Adult Patients With Uncomplicated Urinary Tract Infections due to Enterobacterales. Open Forum Infect Dis. 2021 Oct;8(10):ofab380. [PMC free article: PMC8516593] [PubMed: 34660834]
76.Fuchs F, Hamprecht A. Results from a Prospective In Vitro Study on the Mecillinam (Amdinocillin) Susceptibility of Enterobacterales. Antimicrob Agents Chemother. 2019 Apr;63(4) [PMC free article: PMC6437539] [PubMed: 30917983]
77.Kahlmeter G, Åhman J, Matuschek E. Antimicrobial Resistance of Escherichia coli Causing Uncomplicated Urinary Tract Infections: A European Update for 2014 and Comparison with 2000 and 2008. Infect Dis Ther. 2015 Dec;4(4):417-23. [PMC free article: PMC4675763] [PubMed: 26507395]
78.Kahlmeter G, Poulsen HO. Antimicrobial susceptibility of Escherichia coli from community-acquired urinary tract infections in Europe: the ECO·SENS study revisited. Int J Antimicrob Agents. 2012 Jan;39(1):45-51. [PubMed: 22055529]
79.Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ, Soper DE., Infectious Diseases Society of America. European Society for Microbiology and Infectious Diseases. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 01;52(5):e103-20. [PubMed: 21292654]
80.Dahash BA, Sankararaman S. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Aug 7, 2023. Carnitine Deficiency. [PubMed: 32644467]
81.Jansåker F, Thønnings S, Hertz FB, Kallemose T, Værnet J, Bjerrum L, Benfield T, Frimodt-Møller N, Knudsen JD. Three versus five days of pivmecillinam for community-acquired uncomplicated lower urinary tract infection: A randomised, double-blind, placebo-controlled superiority trial. EClinicalMedicine. 2019 Jul;12:62-69. [PMC free article: PMC6677655] [PubMed: 31388664]
82.Jodal U, Larsson P, Hansson S, Bauer CA. Pivmecillinam in long-term prophylaxis to girls with recurrent urinary tract infection. Scand J Infect Dis. 1989;21(3):299-302. [PubMed: 2756342]
83.Bollestad M, Grude N, Solhaug S, Raffelsberger N, Handal N, Nilsen HS, Romstad MR, Emmert A, Tveten Y, Søraas A, Jenum PA, Jenum S, Møller-Stray J, Weme ET, Lindbaek M, Simonsen GS., (the Norwegian ESBL UTI study group). Clinical and bacteriological efficacy of pivmecillinam treatment for uncomplicated urinary tract infections caused by ESBL-producing Escherichia coli: a prospective, multicentre, observational cohort study. J Antimicrob Chemother. 2018 Sep 01;73(9):2503-2509. [PubMed: 29982514]
84.Jansåker F, Frimodt-Møller N, Sjögren I, Dahl Knudsen J. Clinical and bacteriological effects of pivmecillinam for ESBL-producing Escherichia coli or Klebsiella pneumoniae in urinary tract infections. J Antimicrob Chemother. 2014 Mar;69(3):769-72. [PubMed: 24107388]

Disclosure: Michael Bono declares no relevant financial relationships with ineligible companies.

Disclosure: Stephen Leslie declares no relevant financial relationships with ineligible companies.

Disclosure: Wanda Reygaert declares no relevant financial relationships with ineligible companies.