Continuing Education Activity

Forty percent of women in the United States will develop a urinary tract infection (UTI) at some point in their lifetime, making this one of the most common infections in women. Uncomplicated urinary tract infections, also known as cystitis or lower urinary tract infections, are bacterial infections of the bladder and associated structures. Uncomplicated urinary tract infections occur in female patients with no structural abnormality or comorbidities such as diabetes, old age, pregnancy, or immunocompromised status. Complicated urinary tract infections occur in patients with structural abnormalities or comorbidities such as diabetes, old age, pregnancy, or immunocompromised status. This activity reviews the evaluation and management of urinary tract infections and highlights the role of interprofessional team members in collaborating to provide well-coordinated care and enhance outcomes for affected patients.

Objectives:

• Identify the pathophysiology of UTI.
• Outline the presentation of a patient with a UTI.
• Summarize the management options available for UTIs.
• Review interprofessional team strategies for improving care and outcomes in patients with UTIs.

Introduction

An uncomplicated urinary tract infection (UTI) is a bacterial infection of the bladder and associated structures. These patients have no structural abnormality and comorbidities, such as diabetes, immunocompromised state, or pregnancy. Uncomplicated UTI is also known as cystitis or lower UTI. Bacteriuria alone does not constitute a UTI without symptoms. Typical symptoms include urinary frequency, urgency, suprapubic discomfort, and dysuria. 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. UTIs are uncommon in circumcised males; by definition, any male UTI is usually considered complicated.

Many cases of uncomplicated UTIs will resolve spontaneously, without treatment, but many patients seek therapy for symptom relief. Treatment is aimed at preventing the spread to the kidneys or developing into upper tract disease/pyelonephritis, which can cause the destruction of the delicate structures in the nephrons and eventually lead to hypertension.[1][2][3]

E.coli causes the vast majority of UTIs, followed by Klebsiella, but other organisms of importance include Proteus, Enterobacter, and Enterococcus.[4] The diagnosis of a UTI is made from the clinical history (symptoms) and urinalysis with confirmation by a urine culture, but the proper collection of the urine sample is important.

Etiology

Pathogenic bacteria ascend from the perineum and rectum, predisposing women to urinary tract infections. Women also have shorter urethras than men, which further contributes to their increased susceptibility to UTIs. Blood-borne bacteria cause very few uncomplicated UTIs. Escherichia coli is the most common organism in uncomplicated UTIs by a large margin, followed by Klebsiella.[5][4]

A major risk factor for UTIs is the use of a urinary catheter. Manipulation of the urethra is also a risk factor. Sexual intercourse and the use of spermicides and diaphragms are also risk factors for UTIs. Frequent pelvic exams and the presence of anatomical abnormalities of the urinary tract can also predispose one to a UTI.[6]

UTIs are 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 infections 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 at least four times more frequently in females than males.[7][8]

Pathophysiology

An uncomplicated UTI usually only involves the bladder. When bacteria invade the bladder mucosal wall, an inflammatory reaction called cystitis is produced. The majority of organisms causing a UTI are enteric coliforms that typically inhabit the periurethral vaginal introitus. These organisms ascend the urethra into the bladder and cause UTIs. 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 tend to have a lower risk of a UTI.[9]

Urine is an ideal medium for bacterial growth. Factors that make it less favorable for bacterial growth include a pH of less than 5, the presence of organic acids, and high urea levels. Frequent urination and high urinary volumes are also known to decrease the risk of UTIs.

Bacteria that cause UTIs tend to have adhesins on their surface, which allow the organism to attach to the urothelial 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 an acidic pH, preventing colonization with uropathogens. However, the use of antibiotics can erase this protective effect.

History and Physical

Symptoms of uncomplicated UTIs are pain on urination (dysuria), frequent urination (frequency), inability to start the urine stream (hesitancy), sudden onset of the need to urinate (urgency), and blood in the urine (hematuria). Usually, patients with uncomplicated UTIs do not have fever, chills, nausea, vomiting, or back pain, which are signs of kidney involvement or upper tract disease/pyelonephritis.[6] Clinical symptoms can overlap, and in some cases, it can be hard to distinguish an uncomplicated UTI from a kidney or ore serious infection. When in doubt, treat aggressively for possible upper urinary tract disease.

A urinary tract infection diagnosis is a combination of signs, symptoms, and urinalysis results confirmed with urine cultures. Be wary of medical literature 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 (autonomic dysreflexia) which presents with severe hypertension and headache
• Unexplained fatigue
• Fever
• Cloudly, foul-smelling urine (although odor and cloudy appearance are insufficient for a diagnosis without other symptoms)
• Chills

Patients with permanent indwelling Foley catheters or suprapubic tubes will sometimes tend to have vague symptoms that may include an elevated WBC count and low-grade fever. Most patients with catheters will have pyuria and elevated bacterial colony counts in the urine. This is not a true urinary tract infection (and should not be treated) unless there are systemic signs or symptoms of pain, hematuria, or other abnormal bladder activity.

Evaluation

A good, clean urinalysis (UA) specimen is vital to the workup. A clean catch specimen in non-obese women is preferred. Most obese women cannot give a clean specimen, and epithelial cells in the UA mean 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. This might require a quick catheterization. In-and-out catheterization of the bladder will cause UTI in uninfected women about 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 the sample is left at room temperature, causing an overestimate of the infection's severity.[10][11]

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

Normal urine pH is slightly acidic, with usual values of 5.5 to 7.5, but the normal range is 4.5 to 8.0. A urine pH of 8.5 or 9.0 often indicates a urea-splitting organism, such as Proteus, Klebsiella, or Ureaplasma urealyticum. An alkaline urine pH can signify struvite kidney stones, also known as "infection stones." [12]

The nitrate test is the most accurate dipstick test because bacteria must be present in the urine to convert nitrates to nitrites; this takes 6 hours and is why urologists often request the first-morning urine for testing, particularly in males. The specificity of this test is greater than 90%.[13][14] This test is a direct confirmation of bacteria in the urine, which is a 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 the dipstick LE is a secondary test with a specificity of only 55% for UTIs. 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 infections 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 visible bacteria in uninfected urine, so any bacteria on Gram-stained urine under high field microscopy is highly correlated to bacteriuria and UTIs. A good urine sample with greater than 10 WBC/HPF is abnormal and highly suggestive of a UTI in symptomatic patients.

Urine cultures are not usually required in uncomplicated UTIs according to guidelines but are recommended due to increasing antibiotic resistance and to help differentiate recurrent from relapsing infections. Urine should be cultured in all men and all 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) per milliliter. Recent literature states that a patient who presents with symptoms and greater than 10 CFU/mL is diagnostic of a urinary tract infection. Urine cultures rarely help in the emergency department, except with recurrent UTIs, but can make subsequent treatment easier if patients do not respond to the initial antibiotic prescribed.[15] 

Collecting urine is critical. Midstream voided specimens are very accurate if the patient follows the correct technique. Lactobacilli and squamous cells indicate contamination, and a catheterized specimen may be necessary. In young children and those with spinal cord injuries, suprapubic aspiration may need to be done to collect a proper urine specimen.

Treatment / Management

The treatment has varied historically from 3 days to 6 weeks. There are excellent cure 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 three days is good mini-dose therapy, but resistance rates are high in many areas. It should not be used if local resistance is >20%. First-generation cephalosporins are good choices for mini-dose therapy. Nitrofurantoin is a good choice for uncomplicated UTIs, 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 because of high tissue penetration levels, especially in the prostate. For this reason, fluoroquinolones are not preferred except for complicated infections and those involving the prostate. Recent precautions from the FDA about fluoroquinolone side effects should be heeded.[16][17][18]

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

Even without treatment, most UTIs will spontaneously resolve in about 20% of women, especially if increased hydration is used. The likelihood that a healthy nonpregnant 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 had a transplant, or recently underwent a urological surgical procedure.

Management of recurrent urinary tract infections typically involves optimizing personal hygiene, using vitamin C as a urinary acidifier, taking extra precautions after sexual contact, and using prophylactic antibiotics or antiseptics such as nitrofurantoin and methenamine.[15] Cranberry has also been suggested, and there is some evidence of efficacy. D-mannose has been proposed as a prophylactic agent, but there is insufficient evidence to recommend it. The duration of prophylactic treatment is generally from 6 to 12 months. While this can be extended, there is limited data available.[15] Estrogen vaginal cream applied twice weekly can be helpful in postmenopausal women with atrophic vaginitis.[19]

For relapsing infections (where the organism is identical), a careful examination should be done looking for a source such as a poorly emptying diverticulum or an infected stone.[20]

Treatment of "Recurrent Urinary Tract Infections" and "Complicated Urinary Tract Infections" are covered elsewhere in our companion article.[20]

Differential Diagnosis

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

Prognosis

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

• Poor overall health
• Advanced age
• Presence of renal calculi
• Diabetes (especially if poorly controlled)
• Sickle cell anemia
• Presence of malignancy
• Urethral catheterization
• Ongoing chemotherapy
• Incontinence
• Chronic diarrhea

While mortality rates are low, the morbidity of UTIs is enormous. Besides the annoying symptoms, the cost of management is prohibitive. Missing work and school are common sequelae; sometimes, hospital admission is required because of the severity of the symptoms.

Complications

Complications of urinary tract infections include:

• Persistent lower urinary tract symptoms
• Staghorn urinary calculi
• Pyelonephritis
• Emphysematous pyelonephritis and cystitis
• Incontinence
• Focal renal nephronia
• Renal abscess
• Chronic prostatitis
• Prostatic abscess
• Hypertension
• Renal failure

Deterrence and Patient Education

Patients should be informed of the importance of taking their medication as prescribed and not stopping halfway even if they feel better. They should also be warned not to take prophylactic antibiotics, which will tend to increase resistance.

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 in prevention. Baths should be avoided in favor of showers. A gentle, liquid soap without fragrance should be used in bathing or a liquid baby soap (or baby shampoo, which is very acceptable for the vagina). The soap should be applied using a clean, soft cotton or microfiber washcloth. The vaginal area should be cleaned first to avoid unnecessary contamination of the periurethral area with germs or bacteria. 

Enhancing Healthcare Team Outcomes

UTIs are best managed in an interprofessional fashion, and besides physicians, most nurses will encounter a patient with a UTI. The key to preventing recurrences is patient education. 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 the prophylactic use of antibiotics. Several other non-medical remedies may help some women with UTIs. Anecdotal reports indicate that using cranberry juice and probiotics may help reduce the severity and frequency of UTIs in some women. Primary clinicians should refer patients with recurrent UTIs 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, counsel the patient on compliance, answer any patient questions, and report concerns or results to the clinical team. All team members must follow the patient's progress, and if they observe any issues, including therapeutic failure or adverse events from medication, they need to record their findings in the patient's records and reach out to the appropriate team member(s), so corrective measures can be taken. The earlier UTI is managed, the better the outcomes, and interprofessional team involvement significantly enhances outcomes.[21][22] [Level 5]

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 or those with renal calculi. 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.[23][24] [Level 5]