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Urinary Tract Infection

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Last Update: November 21, 2020.

Introduction

Uncomplicated urinary tract infection (UTI) is a bacterial infection of the bladder and associated structures. These are patients with no structural abnormality and no comorbidities, such as diabetes, immunocompromised, or pregnant. Uncomplicated UTI is also known as cystitis or lower UTI. Forty percent of women in the United States will develop a UTI during their lifetime, making it one of the most common infections in women. UTI is uncommon in circumcised males, and by definition, any male UTI is considered complicated. Many cases of uncomplicated UTI will resolve spontaneously, without treatment, but many patients seek treatment for symptoms. Treatment is aimed at preventing spread to the kidneys or developing into upper tract disease/pyelonephritis, which can cause the destruction of the delicate structures in the nephrons and lead to hypertension.[1][2][3]

E.coli causes the majority of UTI but other organisms of importance include proteus, klebsiella, and enterococcus. The diagnosis of UTI is made from the clinical history and urinalysis, but the proper collection of the urine sample is important.

Etiology

Pathogenic bacteria ascend from the perineum, causing UTI. Women have shorter urethras than men and therefore are more susceptible to UTI. Very few uncomplicated UTIs are caused by blood-borne bacteria. Escherichia coli is the most common organism in uncomplicated UTI by a large margin.[4]

A major risk factor for UTI is the use of a catheter. In addition, manipulation of the urethra is also a risk factor. Sexual intercourse and the use of spermicide and diaphragm are also risk factors for UTI. Frequent pelvic exams and the presence of anatomical abnormalities of the urinary tract can also predispose one to UTI.

UTI is very common after a kidney transplant; the two triggers include the use of immunosuppressive drugs and vesicoureteral reflux. Other risk factors include the use of antibiotics and diabetes mellitus.

Epidemiology

Urinary tract infections are very frequent bacterial infection in women. They usually occur between the ages of 16 and 35 years, with 10% of women getting an infection yearly and more than 40% to 60% having an infection at least once in their lives. Recurrences are common, with nearly half getting a second infection within a year. Urinary tract infections occur four times more frequently in females than males.[5][6]

Pathophysiology

An uncomplicated UTI usually only involves the bladder. When the bacteria invade the bladder mucosal wall, cystitis is produced. The majority of organisms causing a UTI are enteric coliforms that usually inhabit the periurethral vaginal introitus. These organisms ascend into the bladder and cause a UTI. Sexual intercourse is a common cause of a UTI as it promotes the migration of bacteria into the bladder. People who frequently void and empty the bladder have a much lower risk of a UTI.[7]

Urine is an ideal medium for bacterial growth; factors that make it unfavorable for bacterial growth include a pH less than 5, presence of organic acids and high levels of urea. Frequent urination is also known to decrease the risk of UTI.

Bacteria that cause UTI have adhesins on their surface which allow the organism to attach to the mucosal surface. In addition, a short urethra also makes it easier for the uropathogen to invade the urinary tract. Premenopausal women have large concentrations of lactobacilli in the vagina and prevent the colonization of uropathogens. However, the use of antibiotics can erase this protective effect.

History and Physical

Symptoms of uncomplicated UTI are pain on urination (dysuria), frequent urination (frequency), inability to start the urine stream (hesitation), sudden onset of the need to urinate (urgency), and blood in the urine (hematuria). Usually, patients with uncomplicated UTI do not have fever, chills, nausea, vomiting, or back pain, which are signs of kidney involvement or upper tract disease/pyelonephritis. Clinical symptoms can overlap, and in some cases, it is hard to distinguish uncomplicated UTI from a kidney infection. When in doubt, treat aggressively for possible upper renal tract disease. Diagnosis is a combination of signs, symptoms, and urinalysis. Be careful of literature that is based on the results of the urinalysis of asymptomatic patients.

Patients with spinal cord injury or those who are paralyzed may present with:

  • Autonomic instability
  • Fatigue
  • Fever
  • Cloudly, foul-smelling urine
  • Chills

Catheter-associated UTI

Patients with catheters tend to have vague symptoms that include elevated WBC and fever. Most patients will have pyuria and elevated bacterial colony counts in the urine.

Evaluation

A good, clean, urinalysis (UA) specimen is vital to the workup. A clean-catch specimen in nonobese women is preferred. Most obese women cannot give a clean specimen, and epithelial cells in the UA means the urine sample was exposed to the genital surface and did not come directly out of the urethra. Get a clean sample, with very few epithelial cells. In-and-out catheterization of the bladder will cause UTI in uninfected women 1% of the time. Men should start the urine stream to clean the urethra and then obtain a midstream sample. Urine should be sent to the lab immediately or refrigerated because bacteria grow rapidly when a sample is left at room temperature, causing an overestimate of the infection's severity.[8][9]

Do not base the diagnosis upon visual inspection of the urine. Cloudy urine can be aseptic; the cloudiness can come from protein in the sample, not necessarily infection. Crystal clear urine can be grossly infected. All urines undergo dipstick testing, which can be done at the bedside. Helpful values are pH, nitrites, leukocyte esterase, and blood. Remember that in patients with symptoms of UTI, a negative dipstick does not rule out UTI, but positive findings can help make the diagnosis. Look for the presence of bacteria and/or white blood cells (WBC) in the urine.

Normal urine pH is slightly acidic, with usual values of 6.0 to 7.5, but the normal range is 4.5 to 8.0. A urine pH of 8.5 or 9.0 is indicative of a urea-splitting organism, such as Proteus, Klebsiella, or Ureaplasma urealyticum; therefore, an asymptomatic patient with a high pH means UTI regardless of the other urine test results. Alkaline pH also can signify struvite kidney stones, which are also known as “infection stones.”

The most accurate dipstick test is the nitrite test because bacteria must be present in the urine to convert nitrates to nitrites. This takes 6 hours. This is why urologists request the first-morning urine, particularly in males. The specificity of this test is greater than 90%. This is direct confirmation of bacteria in the urine, which is UTI by definition in patients with symptoms. Several bacteria do not convert the nitrates to nitrites, but those are usually involved in complicated UTIs, such as those involving Enterococcus, Pseudomonas, and Acinetobacter.

Leukocyte esterase (LE) identifies the presence of WBCs in the urine. The WBCs release the LE, presumably in response to bacteria in the urine. This is why LE is a subsequent test with a specificity of only 55% for UTI. LE is good at detecting WBCs in the urine, but WBCs can be in the bladder for other reasons, like inflammatory disorders.

Hematuria can be helpful because bacterial infection of the transitional cell lining of the bladder can cause bleeding. This helps distinguish UTI from vaginitis and urethritis which do not cause blood in the urine.

In many labs, the presence of nitrites or leukocyte esterase will automatically trigger a microscopic evaluation of the urine for bacteria, WBCs, and RBCs. On microscopy, there should be no bacteria in uninfected urine, so any bacteria on Gram-stained urine under microscopy is highly correlated to UTI. A good urine sample with greater than 5 to 10 WBC/HPF is abnormal and highly suggestive of UTI in symptomatic patients.

Urine cultures are not needed in uncomplicated UTI. Urine should be cultured in all men and patients with diabetes mellitus, who are immunosuppressed, and women who are pregnant. Classic teaching on urine culture sets the gold standard for infected urine at greater than 10 colony forming units (CFU). Recent literature states that a patient who presents with symptoms and greater than 10 CFU is diagnostic of infection. Urine cultures rarely help in the emergency department, except with recurrent UTI.

Collecting urine is key. Midstream voided technique is very accurate as long as the technique is followed. Presence of lactobacilli and squamous cells indicates contamination. In young children and those with spinal cord injury, suprapubic aspiration is often done to collect urine.

In some patients, catheterization is necessary. At the same time, one should use a bladder scan to assess for post-void residual volume.

Treatment / Management

The treatment has varied historically from 3 days to 6 weeks. There are excellent rates with “mini-dose therapy” which involves three days of treatment. E. coli resistance to common antimicrobials varies in different areas of the country, and if the resistance rate is greater than 50% choose another drug.

Trimethoprim/Sulfamethoxazole for 3 days is good mini-dose therapy, but resistance rates are high in many areas. First-generation cephalosporins are good choices for mini-dose therapy. Nitrofurantoin is a good choice for uncomplicated UTI, but it is bacteriostatic, not bacteriocidal, and must be used for 5 to 7 days. Fluoroquinolones have high resistance but are a favorite of urologists for some reason. Recent precautions from the FDA about fluoroquinolone side effects should be heeded.[10][11][12]

Recently the FDA approved fosfomycin as a single-dose therapy for uncomplicated UTI caused by E coli. Adjunctive therapy with phenazopyridine for several days may help provide symptom relief.

Even without treatment, the UTI will spontaneously resolve in about 20% of women. The likelihood that a female will develop acute pyelonephritis is very small.

Asymptomatic bacteriuria is quite common and requires no treatment, except in pregnant women, those who are immunosuppressed, have undergone a transplant or have undergone a urological procedure.

Differential Diagnosis

  • Pyelonephritis
  • Renal stone
  • Vaginitis
  • PID
  • Herpes simplex

Prognosis

Even with antibiotic treatment, most UTI symptoms last several days. In women with recurrent UTIs, the quality of life is poor. About 25% of women experience recurrences. Factors that indicate a poor outlook include:

  • Overall health
  • Advanced age
  • Presence of renal calculi
  • Diabetes
  • Sickle cell anemia
  • Presence of malignancy
  • Catheterization
  • Ongoing chemotherapy

While mortality rates are low, the morbidity of UTI is enormous. Besides the annoying symptoms, the cost of management is prohibitive. Missing work and school are common reasons and sometimes, admission is required because of the severe symptoms.

Pearls and Other Issues

Although there is no proof of prevention, women should urinate after sexual intercourse because bacteria in the bladder can increase by ten-fold after intercourse. After urination, women should wipe from front to back, not from the anal area forward, which seems to drag pathogenic organisms nearer to the urethra. Vigorous urine flow is helpful to prevention.

Enhancing Healthcare Team Outcomes

UTI is best managed in an interprofessional fashion, and besides physicians, most nurses will encounter a patient with a UTI. The key to preventing recurrences is the education of the patient. Once a UTI has been diagnosed the patient should be encouraged to drink more fluids. Sexually active women should try to void right after sexual intercourse as this can help flush the bacteria out of the bladder. Some women with recurrent UTIs may benefit from prophylactic use of antibiotics. Several other non-medical remedies may help some women with UTI. Anecdotal reports indicate that the use of cranberry juice and probiotics may help reduce the severity and frequency of UTI in some women. Primary clinicians should refer patients with recurrent UTI to the urologist to rule out reflux and anatomical defects. Clinicians should work closely with a pharmacist to ensure the best antibiotic choices for treatment, with the pharmacist verifying appropriate coverage, dosing, and duration. Patient and community safety are affected by ensuring the prescribing of the best antibiotic and medication compliance. Nursing can chart progress and counsel the patient on compliance, as well as answering any patient questions, and reporting concerns or results to the clinical team. The earlier UTI is managed, the better the outcomes, and interprofessional team involvement is a significant enhancement to outcomes. [Level 5] [13][14] (Level V)

Outcomes

The majority of women with a UTI have an excellent outcome. Following treatment with an antibiotic, the duration of symptoms is 2 to 4 days. Unfortunately, nearly 30% of women will have a recurrence of the infection. Morbidity is usually seen in older debilitated patients, those with renal calculi and in patients. Other factors linked to recurrence include the presence of diabetes, underlying malignancy, chemotherapy and chronic catheterization of the bladder. The mortality after a UTI is close to zero. [15][16](Level 5)

Continuing Education / Review Questions

References

1.
Five-day nitrofurantoin is better than single-dose fosfomycin at resolving UTI symptoms. Drug Ther Bull. 2018 Nov;56(11):131. [PubMed: 30297448]
2.
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]
3.
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. [PubMed: 30296501]
4.
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]
5.
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]
6.
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]
7.
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]
8.
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]
9.
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]
10.
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]
11.
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]
12.
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;:1-8. [PMC free article: PMC6536752] [PubMed: 30168406]
13.
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]
14.
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]
15.
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]
16.
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]
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