Kelly A. Healy, MD
Demetrius H. Bagley, MD, FACS
BASICS
DESCRIPTION
• Inflammatory process of the bladder
• Occurs more frequently in women.
• In men, isolated cystitis is rare and often associated with prostatitis that results in secondary bacterial infection of the bladder.
• Clinical syndrome of dysuria, frequency, urgency, and suprapubic pain
• Can be caused by infection (bacterial, viral, fungal, less commonly parasitic), radiation, interstitial cystitis (IC) or due to other irritants (drugs), or a complication of another illness
• Geriatric considerations:
– Bacterial cystitis increases with advancing age.
• Pediatric considerations:
– Cystitis in children is rare. Bacterial cystitis in an infant necessitates a urologic workup.
– Eosinophilic cystitis most common in this age group.
• Pregnancy considerations:
– Bacterial cystitis in pregnancy requires appropriate antibiotic coverage to prevent complications to the mother or fetus.
– Screening and treatment of asymptomatic bacteriuria in pregnant women is encouraged to prevent the development of cystitis or more severe UTI and fet al harm.
EPIDEMIOLOGY
Incidence
• 33% of women experience an episode of bacterial cystitis by age 24. 50% of women will have an episode in their lifetime (1).
• Annual incidence of 0.5–0.7 infections per patient-year in this group
• Bacterial cystitis in healthy men is rare:
– Annual incidence <0.01% in men aged 21–50 yr.
• Hemorrhagic cystitis occurs in 10–15% of patients after bone marrow transplantation while on immunosuppression. The BK virus is present in 80% of population but is reactivated only with immunosuppression (2).
– Adenovirus in the urine preceding transplantation is greatest associated factor
• Reported rates of IC from 52/100,000 to 67/100,000
Prevalence
N/A
RISK FACTORS
• Bacterial cystitis:
– Young women: Sexual activity, use of spermicidal condoms or diaphragm, and genetic factors such as blood type or maternal history of recurrent cystitis
– Healthy, noninstitutionalized older women: Postmenopausal changes in the perineal epithelium and vaginal microflora, incontinence, diabetes, and history of cystitis
Genetics
N/A
PATHOPHYSIOLOGY (3)
• Bacterial cystitis in females is usually an ascending infection.
• In males, it occurs in association with urethral or prostatic obstruction, prostatitis, foreign bodies, or tumors.
• Increases in tumor necrosis factor in bladder mucosa
• Increased mast cell degranulation and histamine release
• Changes in purinergic signaling
ASSOCIATED CONDITIONS
See “Differential Diagnosis.”
GENERAL PREVENTION
• Infectious: Minimize bacterial exposure, avoid indwelling Foley catheter if possible; intermittent catheterization if prolonged catheter needed
• Hemorrhagic: Avoid radiation or cyclophosphamide/iphosphamide exposure
DIAGNOSIS
HISTORY
• Characterization of symptoms: Frequency, urgency, dysuria, suprapubic pain, perineal or scrotal pain, dyspareunia
• Exposure to radiation:
– Obliterative endarteritis causing ischemia
– May occur several years after exposure.
• Exposure to cyclophosphamide/iphosphamide:
– Common cause of hemorrhagic cystitis thought to be due to acrolein metabolite dwelling in bladder
• History of UTI; previous treatments
• If patient immunosuppressed:
– Suspect viral or fungal infection
• Use of personal hygiene products that can cause local irritation (douches, vaginal preparations)
• Indwelling catheters
• History of hematuria
• History of fevers, chills
• Symptoms of vaginitis or discharge present
PHYSICAL EXAM
• Vital signs: Fever, tachycardia (from anemia or sepsis), pallor (anemia due to hemorrhagic cystitis)
• Abdomen: Suprapubic tenderness, costovertebral angle tenderness
• GYN: Bladder or vaginal tenderness, vaginal discharge
• GU, male: Tender and/or boggy prostate, testicular tenderness, penile discharge
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urinalysis with microscopy
• Urine culture:
– Anaerobic, aerobic
Midstream standard
Catheterize sample if concerns about contamination
– Fungal and viral cultures only if high suspicion
– A recent study compared catheterized urine with midstream urine cultures in acute cystitis (4)
Cultures of voided midstream urine with acute uncomplicated cystitis accurately showed evidence of bladder Escherichia coli but not of enterococci or group B streptococci
These bacteria which are often isolated with E. coli but appear to rarely cause cystitis by themselves (urethral contaminants)
• CBC: Anemia in hemorrhagic cystitis, leukocytosis in infectious cystitis
• Creatinine
• Urine cytology: If patient with symptoms of cystitis, risk factors for urothelial or other bladder cancer, and negative workup for UTI or overactive bladder
• Urine culture for Mycobacterium in presence of sterile pyuria and suspicion for TB
• Vaginal discharge evaluation if present
Imaging
• CT urogram or US:
– To rule out associated upper-tract pathology
– May show thickened bladder wall or filling defect such as blood clots or tumor
• Cystogram:
– To rule out vesicoureteral reflux if considering intravesical formalin treatment for hemorrhagic cystitis
Diagnostic Procedures/Surgery
• Cystoscopy for hematuria workup or if the diagnosis is not apparent
• Cystoscopy with hydrodistention for the diagnosis of IC
• Bladder biopsy: To rule out carcinoma in situ or for tissue culture
Pathologic Findings
• Evidence of acute or chronic inflammation
• Michaelis–Gutmann bodies in malakoplakia
DIFFERENTIAL DIAGNOSIS
• Anxiety
• Balanitis
• Bladder cancer or other malignancy
• Chronic pelvic pain syndromes
• Cystitis cystica, cystitis glandularis
• Diabetes insipidus, excess fluid intake
• Diabetes mellitus
• Diuretics, excessive caffeine, alcohol
• Eosinophilic cystitis
• Epididymitis
• Extrinsic bladder compression (eg, pelvic tumor, radiation-induced fibrosis)
• Genital herpes
• Hemorrhagic cystitis
• Infectious cystitis: Bacterial, viral, parasitic, fungal
• IC (painful bladder syndrome)
• Neurogenic bladder, chronic urinary retention
• Overactive bladder
• Prostatitis
• Prostatodynia
• Pyelonephritis
• Urethral syndrome
• Urethritis (eg, gonorrhea, chlamydia)
• Urinary calculi
• Vulvovaginitis and/or pelvic inflammatory disease
TREATMENT
GENERAL MEASURES
• Encourage adequate hydration.
• Proper toilet hygiene for females to limit urethral exposure to pathogens
– Cleansing perineum “from front to back” (controversial)
• Encourage voiding immediately before and after sexual activity in females.
MEDICATION
First Line
• Antimicrobials for bacterial cystitis
– TMP–SMZ for 3 days is a standard therapy for simple uncomplicated bacterial cystitis in females.
– Other combinations may include cephalexin, 250–500 mg q6h for 1–3 days; ciprofloxacin, 250–500 mg q12h for 1–3 days; nitrofurantoin (macrocrystals), 100 mg q12h for 7 days; ofloxacin, 200 mg q12h for 1–3 days
• Phenazopyridine (Pyridium) for relief of dysuria:
– Pregnancy category B
– Contraindicated in glomerulonephritis, renal insufficiency or failure, severe hepatitis, G6PD deficiency
– Side effects: Orange urine, renal failure, rash, nausea, headache, vertigo, hemolytic anemia, methemoglobinemia
– Dose:
Adults: 200 mg PO TID
Pediatric: 4 mg/kg PO TID
Second Line
Based on culture if initial antibiotic not successful in bacterial cystitis
SURGERY/OTHER PROCEDURES
• Cystoscopy with biopsy to diagnose cystitis cystica or glandularis
• Cystoscopy with hydrodistention to diagnose IC; look for characteristic glomerulations.
• Cystoscopy with clot evacuation and electro or laser fulguration for hemorrhagic cystitis
• Cystectomy for refractory hemorrhagic cystitis is rarely necessary
ADDITIONAL TREATMENT
Radiation Therapy
May induce radiation cystitis
Additional Therapies
• Intravesical installations of alum, silver nitrate for hemorrhagic cystitis
• Hyperbaric oxygen for hemorrhagic cystitis.
Complementary & Alternative Therapies
Cranberry tablets for prevention of recurrent bacterial cystitis; evidence that the benefit for preventing UTI is small, cranberry juice cannot currently be recommended for the prevention of UTIs.
ONGOING CARE
PROGNOSIS
Simple bacterial cystitis prognosis is excellent.
COMPLICATIONS
• Depends on etiology of cystitis
• Untreated simple bacterial cystitis can cause pyelonephritis.
• Hemorrhagic cystitis may recur and/or be refractory to therapy, resulting in multiple transfusions or requiring cystoscopy and fulguration.
FOLLOW-UP
Patient Monitoring
• Urinalysis
• History and physical exam
• Females with >3 episodes of cystitis per year should be considered candidates for prophylaxis:
– Prior to institution of therapy, exclude anatomic abnormality (eg, stones, reflux, fistula).
– Single dosing at bedtime or at time of intercourse is recommended.
– Common oral agents are TMP–SMZ (40 mg/200 mg), nitrofurantoin (100 mg), and cephalexin (250 mg).
Patient Resources
http://www.bladderandbowelfoundation.org/bladder/bladder-problems/bacterial-cystitis.aspN/A
REFERENCES
1. Wang A, Nizran P, Malone MA, et al. Urinary tract infections. Prim Care. 2013;40(3):687–706.
2. Rinaldo CH, Tylden GD, Sharma BN. The human polyomavirus BK (BKPyV): Virological background and clinical implications. APMIS. 2013;121(8):728–745.
3. Payne H, Adamson A, Bahl A, et al. Chemical- and radiation-induced haemorrhagic cystitis. Current treatments and challenges. BJU Int. 2013;112(7):885–897.
4. Hooton TM, Roberts PL, Cox ME, et al. Voided midstream urine culture and acute cystitis in premenopausal women. N Engl J Med. 2013;369(20):1883–1891.
ADDITIONAL READING
• Del Pizzo JJ, Chew BH, Jacobs SC, et al. Treatment of radiation induced hemorrhagic cystitis with hyperbaric oxygen: Long-term followup. J Urol. 1998;160(3 Pt 1):731–733.
• Epidemiology of interstitial cystitis. Executive Committee Summary and Task Force Meeting Report. October 29, 2003. NIDDK. (http://archives.niddk.nih.gov/ic2003/TaskForce_Meeting_Report.pdf)
• Hu KK, Boyko EJ, Scholes D, et al. Risk factors for urinary tract infections in postmenopausal women. Arch Intern Med. 2004;164:989–993.
• Sencer SF, Haake RJ, Weisdorf DJ. Hemorrhagic cystitis after bone marrow transplantation. Risk factors and complications. Transplantation. 1993;56(4):875–879.
• Warren JW, Abrutyn E, Hebel JR, et al. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Clin Infect Dis. 1999;29:745–758.
See Also (Topic, Algorithm, Media)
• Bacteruria and Pyuria
• Cystitis, Hemorrhagic (Infectious, Noninfectious, Radiation)
• Cystitis, Radiation
• Interstitial Cystitis
• Prostatitis, General
• Pyuria Algorithm 
• Urinary Tract Infection (UTI), Adult Female
• Urinary Tract Infection (UTI), Adult Male
• Urinary Tract Infection (UTI), Pediatric
CODES
ICD9
• 595.82 Irradiation cystitis
• 595.89 Other specified types of cystitis
• 595.9 Cystitis, unspecified
ICD10
• N30.40 Irradiation cystitis without hematuria
• N30.80 Other cystitis without hematuria
• N30.90 Cystitis, unspecified without hematuria
CLINICAL/SURGICAL PEARLS
• Acute cystitis in females is most commonly bacterial and typically responds to a short course of antibiotic.
• Cystitis in the male is much less common and usually indicates a need for further evaluation.