Acute Cystitis

Etiology

Most UTIs in females are acute uncomplicated cystitis caused by Escherichia coli (86%), Klebsiella species (5%), Staphylococcus saprophyticus (3%), Proteus species (3%), Enterobacter species (1.4%), Citrobacter species (0.8%), or Enterococcus species (0.5%). (In other words, Escherichia coli is by far the most common organism causing urinary tract infections, Klebsiella is the next most likely cause, followed by Proteus.)[2][7] Urethral catheterization accounts for 80% of nosocomial UTIs, and 5% to 10% are related to genitourinary manipulation. Sexual intercourse increases the risk as sexual activity inoculates the bladder with bacteria. Using a diaphragm or spermicide also increases the risk of a UTI as well as new or multiple sexual partners and having the first UTI before 15 years of age.[8][9]

The primary risk factor for acute cystitis in women is the proximity of the female urethral meatus to the anus. This easily contaminates the vulvar and peri-urethral area with bacteria originating from the rectum.[2] The short female urethra is another risk factor as it allows relatively easy access to the bladder.[2] In postmenopausal women, the lack of vaginal estrogen effect is a risk factor.[10]

Epidemiology

Urinary tract infections (UTI) are the most common bacterial infections in women. About 40% to 60% of women experience a UTI at some point in their lives; half by 32 years of age.[2] The abundance of this disease results in eight million emergency or clinic visits, 100,000 hospital admissions, and $3.5 billion annually in healthcare costs in the US.[11] Within a year of an acute urinary infection, 27 to 46% of women will have another UTI. An estimated 30% to 44% of women will have a second UTI within six months of their initial infection.[12]

The incidence in men is far lower, with fewer than 10 cases for every 10,000 men below age 65 yearly.[13] Male symptoms are the same as in women, but recurrent or intractable symptoms suggest possible prostatitis.[2] Besides the longer urethra, men also have a urethral meatus that is further from the contaminated anus, a drier periurethral environment, and urethral as well as prostatic defenses.[2] Traditionally, all UTIs in men were considered complicated, but now it is believed that some may be treated as uncomplicated infections if they are between 15 and 50 years of age and do not have any risk factors such as bladder outlet obstruction, urological anatomical abnormalities, compromised immunity, complicating medical comorbidities (such as renal failure, uncontrolled diabetes or renal transplant), or urolithiasis.[14]

Pathophysiology

Urinary tract infections are caused by bacterial invasion of the urothelium of the bladder, bacteria migrating from the rectum, and colonization of bacteria from the perineum and vagina. Age is an important factor as estrogen diminishes with age, and pH increases, thus promoting colonization of the vagina and perineum with gram-negative enteric organisms such as E. coli.[2]

History and Physical

Patient history is the single most important tool for diagnosing acute uncomplicated cystitis, and it should be supported by a focused examination and urinalysis. It is also important to rule out a more serious, complicated UTI. The new onset of frequency and dysuria, with the absence of a vaginal discharge, has a positive predictive value of 90% for a UTI.[15][16][17][18]

Sign/Symptoms

• Cystitis: Frequency, dysuria, urgency, suprapubic pain, cloudy urine, and hematuria
• Pyelonephritis: Similar symptoms of cystitis but usually will have flank pain, fever, chills, nausea, vomiting, and other systemic symptoms
• Elderly: Apart from a typical presentation, they may tend to have altered mental status, lethargy, and generalized weakness[2]

The presence of a strong odor and/or a cloudy appearance without other symptoms is insufficient to diagnose a UTI or to initiate antibiotic treatment.[19]

Cystitis can be either complicated or uncomplicated, and the workup and treatment are guided by identifying which category of infection is present.[1]   

An uncomplicated UTI is defined as a urinary infection in the absence of anatomical, comorbid, or functional abnormalities in an otherwise healthy, premenopausal, non-pregnant female.[2]

Complicated urinary tract infections are essentially all urinary infections that do not meet the definition of an uncomplicated UTI. These would include anatomical or systemic factors that increase the chance of infection like male gender, poorly controlled diabetes, immunosuppression, renal failure (polycystic kidney), dialysis, hospital-acquired, bladder outflow obstruction (prostatic hypertrophy, urethral stricture), neuropathic bladder (multiple sclerosis, diabetes mellitus), urethral catheterization or ureteral stenting, ureterolithiasis, genitourinary surgery or malignancy, vesicoureteral reflux, and incomplete bladder emptying.[20][21] See our companion article on complicated urinary tract infections for additional details.[21]    

In the elderly, mental status changes alone are not sufficient to make a diagnosis of a UTI. Improving hydration, assessing the patient for other causes, and appropriate observation are indicated.[2]

Management of recurrent UTIs is best reviewed in the American Urological Association Guidelines on Recurrent Urinary Tract Infections.[11]

Relapsing infections (recurrent infections with the same organism) suggest urolithiasis, and appropriate studies (non-contrast CT, renal ultrasound) should be performed.

Physical Exam

A physical examination with acute uncomplicated cystitis is typically normal except in 10% to 20% of women with suprapubic tenderness. Acute pyelonephritis may be suspected if the patient is ill-appearing and seems uncomfortable, particularly if the patient has a concomitant fever, tachycardia, or costovertebral angle tenderness. A pelvic examination should be done in cases of suspected organ prolapse or recurrent UTIs.[2]  

Self Diagnosis and Diagnosis by Telephone

Two recent studies suggest that women who self-diagnose a UTI may be treated safely via telephone management.[22] Women who have been previously treated for acute uncomplicated cystitis are usually accurate and reliable in determining when they are having another episode.

Evaluation

The convenience and cost-effectiveness of a urine dipstick test make it a common diagnostic tool. It is an appropriate alternative to urinalysis and urine microscopy to diagnose acute uncomplicated cystitis. Nitrite and leukocyte esterase are the most accurate indicators of acute uncomplicated cystitis in symptomatic women. Pyuria, bacteriuria, and even positive cultures of >100,000 CFU/mL do not necessarily constitute a diagnosis of a UTI unless there are also urinary or systemic symptoms such as pain, bladder spasms, fever, hematuria, leakage, etc. This is often the case in patients with chronic indwelling catheters.

Urinalysis with microscopy is the gold standard for urinalyses. Ideally, a mid-stream urine catch or a catheterized sample is preferred to avoid possible contamination. However, at least two studies have shown no significant difference in the incidence of contaminated or unreliable results in specimens collected with or without preliminary cleansing.[23][24] The risk of UTI from a single urethral catheterization in previously uninfected women is only about 1%. This should be done if a clean catch sample with few epithelial cells cannot be obtained, as in many morbidly obese females.[1]

Nitrites on the urinary dipstick are the most reliable non-microscopic test for urinary tract infections. Bacteria, usually gram-negative organisms, reduce nitrate to nitrite in the urine, which takes six hours.[1] Under normal circumstances, urine will have no nitrites, making the test fairly reliable. False positives can result from air exposure, and false negatives can result from a non-nitrite producing organism, low nitrate diet (decreased vegetables), vitamin C, overly concentrated urine, and low pH. The nitrite test has an overall sensitivity of 19% to 48% and specificity of 92% to 100%.[25] Only a few bacteria do not perform this conversion, including Enterococcus, Pseudomonas, and Acinetobacter.[1]

Leukocyte esterase can detect the presence of intact or broken down neutrophils on a urinary dipstick. False negatives can result in early infection, excess vitamin C, overly concentrated urine, ketonuria, and proteinuria. False positives can be caused by contamination of the urine by skin flora. Its overall sensitivity is 62% to 98%, and specificity is 55% to 96%. Overall, a useful indicator but not quite as reliable as nitrites.  

Consider treating patients with UTI symptoms empirically if nitrites are positive, but evaluate alternative diagnoses if the leukocyte esterase is negative.[26] Combined positive leukocyte esterase and nitrites had a high positive predictive value of 85% and an even higher negative predictive value of 92%.[26] However, a negative dipstick urinalysis does not definitively eliminate a potential diagnosis of urinary tract infection.[2][27]

Pyuria is defined as more than ten white blood cells (WBC) per HPF. It has a reported sensitivity of 90% to 96% and specificity of 47% to 50%. To some degree, it depends on the quality of the collection, promptness of the examination, and quality of the laboratory technician performing the test, as yeast can sometimes be mistaken for white blood cells.

White blood cell casts consist of a coagulum of Tamm Horsfall mucoprotein and leukocytes from the renal tubular lumen, which is considered an indicator of pyelonephritis. It may also be associated with glomerulonephritis and interstitial nephritis.

Bacteriuria is usually defined as a colony count of more than 100,000 CFU/mL for a single organism from a clean-catch urine sample. However, 20% to 40% of women presenting with cystitis will only have 100-10,000 CFU/mL. If associated with symptoms, the positive predictive value for a UTI is >90%.

Urine cultures are not absolutely required in simple cystitis but highly recommended for bacterial identification and antibiotic selection in case of treatment failure, resistance, or persistent symptoms. Absolute indications for a urine culture include complicated urinary infections, pyelonephritis, and prior antimicrobial treatment. Cultures help differentiate relapsing from recurrent UTIs as well as assist in making proper adjustments to antibiotic selection, duration, and dosage.[2] Urine cultures in patients with UTIs generally have 100,000 CFU/mL, but lower counts do not eliminate a possible urinary tract infection.[2][28][29] 

Urine cultures do not affect treatment in the emergency department, so they are sometimes omitted but are strongly recommended as treatment failures and increasing antibiotic resistance can make follow-up treatment problematic if the initial therapy is unsuccessful.[2] Routine post-treatment urinalysis or urine cultures in asymptomatic patients with simple cystitis are unnecessary. Urine samples for culture should either be immediately sent to the laboratory or refrigerated to avoid accelerated bacterial growth if left at room temperature.[1][30]

Imaging is generally not needed in routine cases of simple, uncomplicated cystitis. In complicated cases, ultrasound can evaluate for hydronephrosis or abscess, and CT can help evaluate for kidney stones, hydronephrosis, emphysematous changes, and abscesses.[11][21]

Cystoscopy is not needed or necessary in routine cases of simple cystitis.[11]

Treatment / Management

There are many things to consider when treating cystitis. The choice between agents should be individualized and depends on the duration of treatment as well as the possible organism involved. According to guidelines, there is no single, best agent to treat acute uncomplicated cystitis. Choosing an antibiotic depends on its effectiveness, the risk of adverse effects, resistance rates, and propensity to cause collateral damage. Physicians should also consider cost, local antibiotic resistance patterns, antibiotic availability, and patient factors, such as allergy history. On average, patients will experience symptom relief within 36 hours of beginning treatment. Increasing antimicrobial resistance, particularly to fluoroquinolones and carbapenems, as well as the emergence of extended-spectrum beta-lactamase (ESBL) producing organisms, have all contributed to making treatment more difficult and complex.[2]

Excellent cure rates can be achieved with only three days of therapy, but longer treatment durations are sometimes recommended. Local resistance patterns will vary, but any drug with a resistance rate of over 50% should generally not be used unless no alternatives are available and culture/sensitivity results indicate efficacy.[1]

Uncomplicated Cystitis

• Nitrofurantoin 100 mg by mouth twice a day for 5 to 7 days as it is bacteriostatic and not bacteriocidal
• Trimethoprim-sulfamethoxazole 160 mg/800 mg twice a day for 3 days (if local resistance is <20%)
• Fosfomycin 3 grams oral once (phenazopyridine can be useful as adjunctive therapy for dysuria)
• Ciprofloxacin 250 mg twice a day or levofloxacin 250 mg twice daily for 3 days (fluoroquinolones are not preferred for first-line therapy in uncomplicated cystitis due to increasing bacterial resistance unless nothing else is appropriate.)
• Alternatives are B-lactams such as amoxicillin-clavulanate 500/125 mg twice a day for seven days or Cephalexin 250 mg four times daily for 3 to 7 days.
• Prophylactic antibiotics may be recommended for patients with complicated or recurrent cystitis but are not routinely recommended for acute, simple cystitis.[21]

Complicated Cystitis

There is no absolute guideline for treatment, but therapy typically requires a longer duration (typically about seven to fourteen days). Please see our companion article on Complicated Urinary Tract Infections.[21] 

Some recommended treatments are listed below.[21] 

Foley Catheters 

• If treating a patient with a catheter for a UTI, the catheter should always be changed to eliminate the biofilm and avoid contaminating the urine culture.
• Catheters develop biofilms after only a few days, so urine cultures should ideally be taken only from newly placed Foleys.
• Treatment is the same as in patients without catheters.
• Gentamicin solution can be used as an additional treatment option in patients with catheters.
• Prophylactic antibiotics are not recommended for patients with catheters but may be used in selected patients at times of catheter changes if appropriate.

Nonpregnant Women

• Nitrofurantoin monohydrate/microcrystals 100 mg mouth twice a day for 5 to 7 days
• Trimethoprim-sulfamethoxazole DS by mouth twice a day for 7 to 10 days
• Ciprofloxacin 500 mg by mouth twice a day for 7 to 10 days if other antibiotics are not acceptable

Pregnant Women

In pregnancy, it is recommended that asymptomatic bacteriuria be treated as well as overt cystitis.[21] Only about 2.3% of pregnant women will develop a symptomatic UTI during their pregnancy.[2] A shorter course of antibiotic therapy is preferred in pregnant patients. Fluoroquinolones are contraindicated during pregnancy. Nitrofurantoin is contraindicated in a pregnant patient at term, during labor, and delivery. Trimethoprim/sulfamethoxazole is not recommended during the first trimester.

• Amoxicillin-clavulanate 500 mg/12 mg by mouth twice a day for 7 days 
• Keflex 500 mg by mouth four times a day for 3 to 5 days
• Cefpodoxime 100 mg twice a day for 5 to 7 days.

Men

Acute cystitis is usually recognized as complicated in men. Men with cystitis who do not have signs or symptoms of prostatitis can be treated with the following regimens:[21] 

• Ciprofloxacin 500 mg by mouth twice a day for 7 days
• Levofloxacin 750 mg by mouth once a day for 7 days
• Trimethoprim-sulfamethoxazole DS by mouth twice a day for 7 to 10 days
• Nitrofurantoin 100 mg by mouth twice a day for 7 days. (Not recommended for suspected prostatitis due to lack of tissue penetration.)

Differential Diagnosis

• Cervicitis
• Epididymitis
• Prostatitis
• Syphilis
• Urethritis
• Vulvovaginitis
• Atrophic vaginitis
• Interstitial cystitis
• Radiation cystitis
• Painful bladder syndrome

Prognosis

Symptoms typically resolve within about three days of initiating antibiotic therapy. Most simple urinary tract infections will resolve spontaneously in about 20% of women, particularly if increased hydration is utilized.[2] Recurrent cystitis will develop in about 25% of women within six months of their simple urinary tract infection. This rate increases if they have had more than one prior UTI.[2] A simple UTI has an excellent prognosis for most women without significant risk factors.

Complications

Complications from simple acute cystitis are relatively rare other than UTI recurrence.

Other possible complications include:

• Acute renal failure
• Antibiotic-resistant organisms
• Chronic prostatitis
• Emphysematous pyelonephritis
• Obstructive pyonephrosis
• Persistent urinary tract symptoms
• Pyelonephritis
• Renal or perinephric abscess
• Renal vein thrombosis
• Sepsis