Daniel C. Parker, MD
Michael A. Pontari, MD
BASICS
DESCRIPTION
• Primary fungal infection of the genitourinary (GU) tract is common with Candida, but uncommon with other fungi.
• Other fungal infections are found in the GU tract but are seen more commonly with immunocompromised patients or in setting of systemic disease.
EPIDEMIOLOGY
Incidence
• Difficult to determine because most cases are not reportable
– Estimated 1–2 new cases per 100,000 population per year involving the GU tract
Prevalence
Difficult to estimate as cases are not reportable
RISK FACTORS
• Urinary tract drainage catheter
• Prior antibiotics
• Diabetes/glucosuria
• Urinary tract pathology
• Malignancy
• Increased age
• Neonates
• Female sex
• Prior surgical procedures
• Immunosuppression
Genetics
No heritable form of transmission
PATHOPHYSIOLOGY
• Funguria to fungemia:
– Can occur with obstruction, reflux, or instrumentation
• Fungemia to funguria:
– Disseminated disease seeds GU tract
Multiple microabscesses develop in the renal cortex, with subsequent penetration into the glomeruli and shedding into the urine from the proximal tubules
ASSOCIATED CONDITIONS
• Immunocompromised state:
– Diabetes
– AIDS
• Anatomic GU abnormalities:
– Strictures
– Prostatic hypertrophy
– Diverticula
– Indwelling tubes
– Stones
GENERAL PREVENTION
• Remove unnecessary catheters/tubes
• Narrow antibiotic coverage
• Improve nutritional status
• Control hyperglycemia
DIAGNOSIS
HISTORY
• Immunocompromised state:
– Fungi are ubiquitous in the environment and can overwhelm those with weakened immune systems
– Those receiving chemotherapy, with AIDS, or afflicted with diabetes
• Recent antibiotic use:
– Risk of candiduria is 6× after use of broad-spectrum antibiotics
• Indwelling GU tubes or prosthesis:
– Risk of candiduria 12× with catheterization
• GU tract abnormalities:
– Risk of candiduria 6× with abnormalities (1)[A]
• Occupation:
– Exposure to aerosolized soil; spelunkers; bird handler
• Recent travel or recreation (see image):
– Blastomycosis found in Ohio, Missouri, and Mississippi river basins; Great Lakes; Canada
– Coccidioidomycosis found in semiarid regions of the Western US, Mexico, Central and South America
– Histoplasmosis found in Midwestern and Southern US in areas of high-nitrogen soil such as chicken coops and bat caves
– Cryptococcus thrives with birds
• UTI symptoms:
– Only 4–14% with symptomatic candiduria
PHYSICAL EXAM
• CVA tenderness
• Abdominal tenderness
• Boggy or firm prostate
• Firm testicular or epididymal masses
• GU tubes present
• Manifestations of disseminated disease
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Candida:
– No studies have established the importance of pyuria or quantitative urine culture in diagnosing Candida UTI (2)[A]
– Presence of pyuria helpful in those without catheter, however, up to 25% with candiduria also have bacteriuria/pyuria
– Urine cultures positive for candiduria in otherwise asymptomatic patients should be repeated with a clean catch sample to rule out contamination (2)[B]
– >10,000 CFU/mL could mean infection; 10,000–100,000 CFU/mL could mean colonization
– Check urine microanalysis looking for casts containing yeast: Very specific, not sensitive
• Aspergillosis:
– Culture in Sabouraud medium or stain tissue with methenamine silver or Periodic acid–Schiff stain (PAS); can PCR
• Cryptococcosis:
– Culture; stain tissue with India ink, PAS, methenamine silver; perform latex agglutination
• Phycomycosis:
– Stain tissue
• Blastomycosis:
– Stain tissue and visualize secretions
• Coccidioidomycosis/histoplasmosis:
– Culture and stain tissue
Imaging
CT abdomen with contrast and delayed imaging vs. US may elucidate bezoars, perinephric pathology, renal destruction
Diagnostic Procedures/Surgery
• Cystoscopy/retrograde urogram
• Urine culture
• Tissue biopsy
Pathologic Findings
Positive histology staining for fungi in tissue
DIFFERENTIAL DIAGNOSIS
• Blood clots in collecting system
• Cystitis
• GU TB
• Nephrolithiasis
• Squamous cell carcinoma (SCC)
• Urothelial carcinoma (transitional cell carcinoma)
TREATMENT
GENERAL MEASURES
• Infectious Diseases Society of America recommends treatment of candiduria in (3)[A]:
– Infants with low birth weight
– Patients who will have GU procedures
– Neutropenic patients
– Symptomatic patients
• Treat UTI symptoms empirically for funguria only if the patient is unable to vocalize or perceive symptoms
• Asymptomatic candiduria: Assess for risk factors (3)[A]
MEDICATION
First Line
• Aspergillosis:
– Amphotericin B 1–1.5 mg/kg/d for 10 wk
• Blastomycosis:
– Itraconazole 200 mg PO BID for 6–12 mo
• Candidiasis:
– Clotrimazole, miconazole, tioconazole, terconazole topical for 1 wk
• Candidemia (treat for 2 wk after afebrile and Cx negative):
– Fluconazole 400–800 mg/d IV, then PO
• Candiduria:
– Fluconazole 200 mg/d IV/PO for 1–2 wk
• Coccidioidomycosis:
– Itraconazole 200 mg PO BID. for 1 yr
• Cryptococcosis:
– Amphotericin B 0.5–1 mg/kg/d IV + flucytosine 100 mg/kg/d PO for 2 wk
Then fluconazole 400 mg/d PO for 8 wk OR
Then Itraconazole 200 mg PO BID for 8 wk
– For cryptococcal suppression:
Fluconazole 200 mg/d PO OR
Amphotericin B 0.5–1 mg/kg IV every week
• Histoplasmosis:
– Itraconazole 200 mg PO BID for 6–18 mo
– For histoplasmosis suppression:
Itraconazole 200 mg/d PO BID OR
Amphotericin B 0.5–1 mg/kg IV every week
• Mucormycosis:
– Amphotericin B 1–1.5 mg/kg/d IV for 6–10 wk
Second Line
• Aspergillosis
– Voriconazole 6 mg/kg q12h for 2 days, then 4 mg/kg q12h (IV or oral) for 10 wk OR
– Itraconazole 200 mg IV BID for 4 days, then 200 mg/d IV for 12 days, then 200 mg PO BID for 10 wk OR
– Itraconazole 200 mg PO TID for 9 days, then 200 mg PO BID for 10 wk
• Blastomycosis
– Amphotericin B 0.5–1 mg/kg/d for 6–12 wk OR
– Fluconazole 400–800 mg/d PO for 6–12 mo
• Candidiasis
– Fluconazole 150 mg in 1 dose
• Candidemia (treat until 2 wk after afebrile and Cx negative):
– Caspofungin 70 mg/d IV in 1 dose, then 50 mg/d OR
– Amphotericin B 0.5–1 mg/kg/d
• Candiduria:
– Amphotericin B 0.3–0.5 mg/kg/d IV for 1–2 wk OR
– Flucytosine 25 mg/kg/d PO for 1–2 wk
• Coccidioidomycosis:
– Fluconazole 400–800 mg/d PO for 1 yr OR
– Amphotericin B 0.5–0.7 mg/kg/d IV for 1 yr
• Histoplasmosis:
– Fluconazole 400–800 mg/d PO for 6–18 mo OR
– Amphotericin B 0.5–1 mg/kg/d IV for 10–12 wk
SURGERY/OTHER PROCEDURES
• Obstructions from fungal bezoars require drainage.
• Access to upper tracts can facilitate drainage, antifungal irrigation, and extraction if needed.
• Perinephric abscess can be drained percutaneously, but may require operative drainage if multiple loculations are present.
• Severe aspergillus kidney infections may require nephrectomy.
• Treatment of fungal prostatitis may require surgical intervention for prostate resection or drainage of abscess in addition to medical therapy (4)[B].
ADDITIONAL TREATMENT
Radiation Therapy
None
Additional Therapies
• Irrigation may be necessary in aggressive infections when systemic medication is not excreted into the urine
– Amphotericin B GU tract irrigation
50 mg in 1,000-mL water at 40 mL/hr (over 24 hr) for 5–7 days
– In children, renal irrigation with 10–24 mg/d
• Removing catheter may eradicate funguria in 40% of cases
Complementary & Alternative Therapies
None
ONGOING CARE
PROGNOSIS
• Candiduria does not predict development of candidemia in most people
– Rates 1.3–10.5%
– No different in renal transplant population: 5%
• Aspergillosis mortality 40–90% with treatment
• Phycomycosis (mucormycosis, zygomycosis) mortality 90% if untreated, 24% with nephrectomy and amphotericin B
COMPLICATIONS
• Bezoar formation
• Emphysematous pyelonephritis
• Obstruction, fungemia, death
• Papillary necrosis
• Perinephric abscess
• Renal scarring
FOLLOW-UP
Patient Monitoring
• Surveillance cultures can be obtained to document clearance of infection.
• Prostate can be fungal reservoir for recurrent infection.
Patient Resources
CDC Fungal Infections Fact Sheet http://www.cdc.gov/ncezid/dfwed/PDFs/fungal-factsheet-508c.pdf
REFERENCES
1. Achkar JM, Fries BC. Candida infections of the genitourinary tract. Clin Microbiol Rev. 2010;23:253–273.
2. Kauffman CA, Fisher JF, Sobel JD, et al. Candida urinary tract infections—diagnosis. Clin Infect Dis. 2011;52:452–456.
3. Fisher JF, Sobel JD, Kauffman CA, et al. Candida urinary tract infections—treatment. Clin Infect Dis 2011;52:S457–466.
4. Wise GJ, Shteynshlyuger A. How to diagnose and treat fungal infections in chronic prostatitis. Curr Urol Rep. 2006;7:320–328.
ADDITIONAL READING
• Kauffman CA. Candiduria. Clin Infect Dis. 2005;41:S371–S376.
• Kauffman CA, Vazquez JA, Sobel JD, et al. Prospective multicenter surveillance study of funguria in hospitalized patients. The National Institute for Allergy and Infectious Diseases Mycoses Study Group. Clin Infect Dis. 2000;30:14–18.
• The Medical Letter: Antifungal drugs. Treatment Guidelines from The Medical Letter 2005;30:7–14.
• Pappas PG, Rex JH, Sobel JD, et al. Guidelines for treatment of candidiasis. Clin Infect Dis. 2004;38:161–189.
See Also (Topic, Algorithm, Media)
• Candidiasis, Cutaneous, External Genitalia
• Candiduria Algorithm 
• Cryptococcus, Genitourinary
• Filling Defect, Upper Urinary Tract (Renal Pelvis and Ureter)
• Fungal Infections, Genitourinary Algorithm
• Fungal Infections, Genitourinary Image 
• Histoplasmosis, Genitourinary
• Urinary Tract Infection (UTI), Adult Female
• Urinary Tract Infection (UTI), Adult Male
• Urinary Tract Infection (UTI), Pediatric
CODES
ICD9
• 112.1 Candidiasis of vulva and vagina
• 112.2 Candidiasis of other urogenital sites
• 116.0 Blastomycosis
ICD10
• B37.3 Candidiasis of vulva and vagina
• B37.4 Candidiasis of other urogenital sites
• B40.89 Other forms of blastomycosis
CLINICAL/SURGICAL PEARLS
• When fungal infections are found in the GU tract in patients without risk factors, a search for systemic disease is warranted.
• Disseminated fungal disease can seed the GU tract through the development of renal microabscesses.
• Fungal infections are encountered in varying geographic locales based on type.
• Treat candiduria in infants with low birth weight, those undergoing GU procedures, neutropenic patients, and symptomatic patients.
• Surgical drainage of fungal infections is indicated in cases of urinary tract obstruction.