Acute cystitis often presents with urinary symptoms which include dysuria, urinary frequency urgency, suprapubic pain or tenderness, and occasionally hematuria. Based on a systematic review examining history and examination findings of women with uncomplicated UTI, the combination of dysuria and urinary frequency in the absence of vaginal discharge or irritation is highly predictive of uncomplicated cystitis. Symptoms may be subtle or atypical in the very young and the very old. Elderly patients with UTI may present with confusion or altered mental status.

Patients with complicated acute cystitis will often present in a similar manner to uncomplicated cystitis. Certain patient populations with complicated cystitis may have atypical symptoms. For example, patients with multiple sclerosis occasionally present with acute neurologic deterioration while those with spinal cord injury may present with autonomic dysfunction or increased spasticity.

Cystitis may be differentiated from pyelonephritis by the absence of systemic findings such as fever, chills, or sepsis. Findings such as flank pain, costovertebral angle tenderness, nausea, and vomiting are also more indicative of upper UTI or pyelonephritis.

When evaluating a patient with symptoms of UTI, it is important to obtain history on any previous episode of UTI, any recent antibiotic use, or any other risk factors that may predispose one to complicated infection such as diabetes, immunocompromised status, recent urologic procedures or instrumentation, renal transplantation, history of kidney stones, history of anatomical or functional urinary tract abnormalities, or pregnancy.

The diagnosis of acute cystitis is usually made clinically in a person with signs and symptoms consistent with a lower UTI in combination with laboratory evidence of pyuria. Physical examination findings are often not necessary for the diagnosis of cystitis but may be more important for patients with pyelonephritis. Often in young, nonpregnant women who have typical symptoms of cystitis and especially in the absence of vaginal discharge or irritation, clinical suspicion may be sufficient in making the diagnosis and in initiating treatment without laboratory confirmation.[8][1][9][10]

Urinalysis, when indicated, is the most important laboratory test in the diagnosis of UTI. Pyuria, which is the presence of at least 10 WBCs or leukocytes in an unspun midstream urine specimen, is almost always present. The absence of pyuria is indicative of an alternative diagnosis. Urine dipsticks may also be used in the diagnosis of UTI. They detect the presence of leukocyte esterase, an enzyme produced by leukocytes, and nitrite, which is indicative of the presence of the Enterobacteriaceae. A positive dipstick test for leukocyte esterase or nitrite is most helpful in patients with typical symptoms of acute cystitis. A negative dipstick test, however, does not reliably rule out a diagnosis of UTI.[11][12][5]

A urine culture is useful for identifying the etiologic pathogens and for determining antimicrobial susceptibility profiles. Greater than or equal to 100000 CFU/mL indicates clinically relevant bacteriuria, but the growth of greater than or equal to 1000 is considered significant in men and samples obtained through straight catheterization. In cases of acute uncomplicated cystitis, however, urine culture is often unnecessary and not routinely done. Urinalysis and urine culture must be performed prior to therapy in all men who present with symptoms of acute cystitis and all women who have risk factors for complicated UTI. They are also indicated in patients with atypical symptoms, and in those who do not respond to treatment or who have a recurrence of symptoms within 2 to 4 weeks. A pregnancy test must be done in women of childbearing age. Men who have recurrent episodes of cystitis must undergo evaluation for prostatitis. In young men who are sexually active with a single episode of cystitis, urologic evaluation is often not indicated. Any risk factors for complicated UTI should, however, prompt urologic evaluation and workup.

Patients who have complicated cystitis and who do not respond after 48 to 72 hours of appropriate antimicrobial treatment will require further evaluation through radiographic imaging of the upper urinary tract. This may be in the form of computed tomography or ultrasonography. CT imaging is usually the test of choice and is more sensitive in the detection of processes that may interfere with treatment response such as obstruction, stone formation, or abscess formation. Ultrasound of the kidneys may be adequate in patients who should not be exposed to radiation.

Acute cystitis is treated with antibiotic therapy. The selection of an antimicrobial agent depends on a patient’s risk factors for infection with a multidrug-resistant (MDR) organism. Patients who are at low risk for resistant etiologic organisms are treated with 1 of the first-line or preferred antimicrobial agents which include:

• Nitrofurantoin 100 mg twice a day for 5 days
• Trimethoprim-sulfamethoxazole (TMP-SMX) double strength twice a day for 3 days
• Fosfomycin 3 gm as a single oral dose
• Pivmecillinam 400 mg twice a day for 5 to 7 days (if available)

Antimicrobial selection should be individualized based on patient factors which include allergy, adverse effects, tolerability, local resistance patterns, cost, or recent use of a specific antimicrobial agent within the preceding three months. Nitrofurantoin should not be used in patients with creatinine clearance of less than 30 mL per minute and TMP-SMX must be avoided in places with regional resistance greater than 20%. The suspicion for pyelonephritis or complicated UTI also precludes the use of nitrofurantoin, fosfomycin, and pivmecillinam because of poor penetration into the renal tissue.[5][13]

Alternative or second-line antimicrobial agents are used in acute cystitis in patients with factors or circumstances that prevent the use of the first-line agents. A 5 to 7-day course of oral beta-lactams such as amoxicillin-clavulanate 500 mg twice daily, cefpodoxime 100 mg twice daily, cefdinir 300 mg twice daily, cefadroxil 500 mg twice daily, and cephalexin 500 mg twice daily (although this agent is less well-studied) is usually preferred. If beta-lactam agents are contraindicated, a fluoroquinolone such as ciprofloxacin or levofloxacin for 3 days may be used.

Urine culture and sensitivity testing are required to guide antimicrobial regimen in patients who are at risk for MDR organisms. Risk factors include a previous MDR isolate (resistant to three or more antimicrobial classes), recent stay in a healthcare facility, recent travel to areas with high prevalence of MDR organisms, or recent use of broad-spectrum antimicrobial agents in the past three months. The appropriate empiric regimen includes nitrofurantoin, fosfomycin, and pivmecillinam (if available). An alternative approach would be to defer treatment until culture and susceptibility results are available especially if factors preclude the use of any of the above said first-line agents.

Symptomatic treatment with analgesics may be used in patients who present with severe dysuria. Phenazopyridine is a urinary analgesic used in short-term treatment of urinary dysuria or discomfort.

Cystitis in men is uncommon and not very well studied. In a healthy man without any risk factors for complicated UTI or without any symptoms suggestive of infection outside the bladder, the treatment approach should be the same as that in women with uncomplicated UTI. For men who have severe symptoms, anatomical or urologic abnormalities, or suspicion of prostate involvement, a fluoroquinolone should be used for empiric therapy pending culture and susceptibility testing results.

Patients who do not respond to antimicrobial regimen after 48 to 72 hours or who have a recurrence of symptoms within a few weeks will require further evaluation including consideration of other potential causes or infection with resistant organisms. Urine culture and susceptibility testing must be obtained, and patients must be treated with a different empiric antimicrobial agent with the subsequent tailoring of the regimen based on susceptibility results.

In female patients who present with dysuria, differential diagnoses include vaginitis and urethritis. Vaginitis is usually associated with vaginal discharge, dyspareunia, and pruritus and causes include bacterial vaginosis, trichomoniasis, or yeast infection. Painful bladder syndrome may be considered in patients with persistent symptoms of bladder discomfort but with no evidence of infectious etiology. This is, however, a diagnosis of exclusion. In men with lower UTI symptoms, prostatitis must be ruled out especially when associated with fever, malaise, perineal pain, and obstructive urinary symptoms. Recurrent UTIs in male patients should heighten suspicion for chronic bacterial prostatitis.

Patients with uncomplicated cystitis typically have improvement of symptoms within 3 days after initiation of antibiotic therapy. Recurrent cystitis occurs in 25% of women within 6 months after the first UTI and the rate increases in women with more than one prior UTI. Complications are rare especially in patients who are appropriately treated. Bacteremia and sepsis from uncomplicated cystitis are uncommon. Emphysematous cystitis is a rare but serious complication of lower UTI. It is associated with the gas formation in the bladder wall and may be potentially fatal if not adequately managed. Risk factors include diabetes, immunocompromised conditions, urinary abnormalities, urinary obstruction, indwelling urinary catheter, and chronic UTIs. In cases of necrotizing infection, surgical intervention may be required.

Cystitis is a commonly encountered disorder by the nurse practitioner and primary care provider. The diagnosis and management are relatively straight forward in most patients. However, there are other patients with structural abnormalities, diabetics and those with spinal cord problems who are more difficult to manage because of recurrent cystitis. Hence, an interprofessional team with an interprofessional treatment approach is necessary to improve outcomes.

Patient education is the key and all clinicians who manage patients with cystitis should encourage an increase in fluid intake. Several studies show that an increase in fluid intake reduces the risk of recurrent infections. The pharmacist should educate the patient on medication compliance.

The nurse practitioner should educate sexually active women to void after sexual intercourse as this has been shown to lessen the risk of a bacterial infection.

Any patient that has recurrent infections should be referred to the urologist for more workup. Only with open communication between members of the interprofessional team can the morbidity of cystitis be lowered.

Outcomes

Patients with uncomplicated cystitis typically have improvement of symptoms within 3 days after initiation of antibiotic therapy. However, recurrent cystitis occurs in 25% of women within 6 months after the first UTI and the rate increases in women with more than one prior UTI. Complications are rare especially in patients who are appropriately treated. When males present with a first-time episode, a referral to a urologist should be made to ensure that there is no structural abnormality.  Individuals who are immunosuppressed, diabetic, have chronic catheterization or are on steroids have the potential to develop sepsis and should be closely monitored and managed by an infectious disease expert.[14]