Fungal Fungal Urinary Tract Infections Urinary Tract Infections

Diagnosis and Diagnosis and ManagementManagement

Tristan T. Berry, M4Tristan T. Berry, M4

Medical College of VirginiaMedical College of Virginia

Objectives

• History

• Definition of the fungal UTI.

• Epidemiology

• Predisposing conditions

• Presenting symptoms

• Common organisms and important rare organisms

• Diagnosis imaging ,cytology/culture (blood and urine)

• Treatment

• Resistance to antifungals

History1890 Schmorl reports renal involvement in patient

with disseminated candidiasis.

1910 Rafin recognizes candidal cystitis

1931 Lundquist reports primary renal mycosis

1948 Moulder reports cystoscopic findings of candidiasis in the urinary bladder

1963 Twelve cases of candidal infection of the kidney reported

1980 Increased reporting of fungal infection of urinary tract . Likely multifactorial.

Epidemiology and Predisposing Factors

Fungal pathogens are the cause of increasing nosocomial infections in

hospital communities.

Epidemiology and Predisposing Factors

From 1980-1990 the nosocomial fungal infection

rate for urinary tract infections had risen from

9.0 to 20.5 per 10,000 hospitalized patients.

Epidemiology and Predisposing Factors

1) Opportunistic organisms

2) Environmental

3) Rare and unusual

Three distinct groups of pathogens are noted for causing fungal UTIs:

Opportunistic Organisms

• normally inhabit human flora or environment.

• proliferate when there is a defect in an individual's immune system. Thus causing disease.

• Candida species - saprophytes of the skin, oropharyx ,gasrointestinal tract and genital regions.

Environmental• include Blastomyces, Histoplasmosis,

Coccidoides.

• found primarily in soil,environment and guano. inhabit human flora or environment.

Rare and unusual

• Mucormycosis and others

Opportunistic Fungi

C. Albicans

• oval yeast with a single bud.

• in tissues it may appear as pseudohyphae or yeasts.

• since Candida is part of normal human flora it is not transmitted.

C. Albicans

Pathogenesis

• Most common opportunistic fungi.

• Causes thrush, vaginitis, chronic mucocutaneous candidiasis

• When local or systemic host defenses are impaired, disease may result.

Pathogenesis

• may disseminate to multiple organs esp. in IVDA and right sided endocarditis.

• kidney is the most commonly involved organ with systemic fungal infection. >85%

• Accounts for 6.9% of nosocomial infections

Pathogenesis

• Candida Spp are the most common organisms causing fungal UTI.

• Candida albicans accounts for 74%

• Glabrata 8%

• Parapsolosis7%

• Tropicalis 3%

Predisposing Conditions

1) Diabetes (impaired phagocytic and fungacidal function of neutrophils)

2) Protracted course of antibiotics

Predisposing Conditions

4) Neoplasm

5) Oral contraceptives

6) Elderly Population

7) Infants- due to immature T-Cell defense

8) Chronic indwelling catheter

Symptoms

• Frequency, dysuria and stranguria

• Pyuria , hematuria or pneumaturia

• classic findings of pyelonephritis, fever, flank pain and CVAT

• high index of suspicion b/c fungal UTI may present like bacterial UTI.

Diagnostic Features

• microscopic urine studies

• urine culture can be helpful for species identification and sensitivities

• Urine colony counts (significant if >105 without indwelling urinary catheter)

Simple vs.

Complex UTI

Simple UTI• Confined to urinary bladder and urethra. • Pt may present with cystitis.(2% of UTIs)• Cystoscopy may present with white patches on

bladder wall.• Bladder wall edema and erythema may be present.• Bladder infections can lead to rupture. (rare)• Microscopic: Inflammatory cells, yeast forms and

pseudohyphae may be present

Treatment• Bladder irrigation with Amphotericin B 50mg/1L water x10-14

d• Effective in 80-92% of patients• Nystatin and Miconazole useful. -poor colloid dispersion in

Nystatin-limits use• Surgical intervention may be required in the form of mucosal

debridement• Removal of large fungal bezoars if present.

Complex UTI

• Complex infections affect the kidneys and ureters

• Result of either hematogenous spread or ascending from lower tract infections

• Associated with fungal accretions that may lead to obstructive uropathy.

Complex UTI

• May lead to persistent candiduria.

• High potential for disseminated infection

• Approximately 88% present with fever and flank pain

• 88% associated with hydronephrosis

• 81% associated with fungemia

Imaging• U/S, Excretory urography, • Retro pyelogram • CT • Renal Scintigraphy

Imaging studies typically exhibit filling

defects of the urinary system

Treatment• Localized

Amphotericin B irrigation for infection of the collecting system..

• Systemic or multifocal infection

IV Ampho B 6mg/kg (Gold Standard) , Fluconazole 100mg BID x 10 days

5-FC- 150mg/kg- high resistance

CASE • HPI:56 year old male with 4 day history of

fever , N/V and diffuse abdominal pain. Anuria 24 hrs prior to admission to the hospital.

• PMH- Diabetes type II diagnosed 5 years prior, controlled with insulin. UTI 6 months prior tx’d with abx.

CASE• Exam- pt. was febrile & appeared acutely ill.

Dry mucous membranes

Diffusely tender abdomen

Bilateral CVAT

• LABS:

Leu =25x10^9 with 82% pmns

BUN 82, Creat 7.9 Glu 280

CASE• U/A: Numerous leukocytes per hpf

Many yeast forms.

• Pt was initially treated with Ampicillin and Ciprofloxacin. IVF and IV insulin.

• Symptoms persisted.

CASE • U/S- bil. hydonephrosis• Cystoscopy with RPG was unsuccessful due to

bilateral ureteral obstruction.• Bilateral percutaneous nephrostomy tubes were placed

(turbid yellow/white urine was recovered.• Antegrade pyelogram- dilation of renal pelvises and

ureters. Multiple filling defects.

CASE • Urine culture- C.Tropicalis 10^4 - 10^5

• Blood cultures on admission were negative for fungi or bacteria.

• Treatment: IV Amphotericin B, direct Ampho B through nephrostomies.

• Fragmentation of fungal balls by guide wire manipulation.

CASE • Therapy cont.for 3 weeks until U/C were

negative.

• Dc’d with Creatinine of 2.1mg/dL.

• No evidence of hydronephrosis at 6 month follow up.

Cryptococosis• Organism: Cryptococcus neoformans• Properties: oval, budding yeast• Epidemiology: Occurs widely in nature, found in pigeon

droppings• Transmission: Inhalation of organism• Clinical manifestations: Pulmonary infection to virulent

pneumonia & meningitis.

Cryptococosis• Predisposition: HIV, DM, lymphoma, ETOH abuse

• GU involvement:

Adrenal-infarction

Renal- pyelonephritis,abscess

Prostate- bladder outlet obstruction or prostatitis

Penis- ulcers of glans

Cryptococosis• Tx: Adrenal-Amphotericin B• Renal- IV Amphotericin B• Prostate-Fluconazole 200-600mg/d x 4 wks• Penis- Resection followed by systemic Ampho B

Apergillosis• Organism: A. fumigatus and A.Flavus• Properties: Only mold form (V shaped branches)• Epidemiology: Widely distributed in nature.

Grow on decaying vegetables. Linked to hospital construction and central air conditioning .

• Transmission: Airborne conidia.

Apergillosis• Predisposition: abraded skin, wounds, cornea, ext.

ear and sinuses, immunocompromised• GU involvement: Renal- DM, malignancy or AIDS

(Fever, CVAT, obstructive uropathy)

Prostate and Genital-DM, Met colon ca, steroid use & AIDS

• DX:Isolation from urine,semen or tissue.

Apergillosis-Treatment

• Systemic Amphotericin B for 3 months Kidney-Percutaneous aspiration, nephrostomy & J- stents

• Very little data to support use of itraconazole

Environmental Fungi

Coccidioidomycosis• Organism: Coccidioides immitus• Properties:dimorphic exists as mold in soil and spherule in

tissue• Location: Western U.S and Mexico. Thrives in arid desert

regions.• Transmission: Airborne infection of the pulmonary

system

Coccidioidomycosis• Clinical manifestations: mild influenza or flu like

illness Valley fever.• Predisposition: Age >65 and HIV+• Disseminated infection: less than 1% of

pulmonary infection become disseminated• Men, pregnant women, immunocompromised and

non white persons more likely to have disseminated infection

Coccidioidomycosis• GU involvement:

• : kidney disease in 36-46% of persons with disseminated disease-microbscess & granulomas

• prostate in 3-6%

• GU manifestations: Voiding dysfunction

Scrotal swelling

Hematuria

Pneumaturia

Histoplasmosis• Organism: H. Encapsulatum

• Properties: dimorphic- mold in soil; yeast in tissues

• Epidemiology: endemic in central and eastern states, esp Mississippi and Ohio grows in soil contaminated with bird droppings and guano.

• Transmission and pathogenesis: Inhaled spores are engulfed by macrophages and develop into yeast forms.

Histoplasmosis• Majority of involvement is spleen and liver.

Pulmonary involvement results in cavitary lesions.

• Clinical manifestations: pneumonia

• Predisposition: HIV+, transplant pts & children.

Histoplasmosis• GU involvement: • Kidneys- noncaseating granulomas,cutaneous fistulas.

• Adrenal-Addison’s dz- will require hormone replacement.

• Prostate- Abscesses

Histoplasmosis

• Dx- Identification of organism in urine,semen or tissue. Culture or skin test.

• Tx- IV Amphotericin B(>2g) total dose followed by long term Itraconazole 200mg/d x12 wks

• Surgical management- Surgical excision or drainage of prostate abscess.

Blastomyces

• Organism: Blastomyces dermatitidis

• Properties: Dimorphic, mold in soil, yeast in tissue

• Broad-based budding

• Epidemiology: North and Central America, also Africa. Grows in moist soil.

Blastomyces• Transmission: Inhalation of mold form. Primarily affects

lungs, skin, bone and CNS• Manifestations: flu-like illness, high fever, respiratory

illness that mimics TB or Cancer• Often subclinical infection.• GU- prostate, epididymis, tubo-ovarian abscess

Blastomyces

• Dx: Fungus in urine, semen or

• Detection of blastomyces A antigen by immunodiffusion.

• Tx: Ketoconazole 400mg/d x 12mos for prostate and epididymis involvement. Amphotericin B for disseminated infxn and immunocompromised

Rare Fungi

Mucormycosis

• Organism- Mucor

• Properties-mold

• Epidemiology-widely in nature

• Transmission- Inhalation of airborne spores

• Predisposition- DKA,AIDS, liver abnormalities

Mucormycosis

• Manifestations- primarily rhino cerebral, sinusitis and brain hemorrhage

• GU- Primarily fever and flank pain• Dx- biopsy showing mold with nonseptate hyphae• Tx-IV amphotericin B >1gram for 1 month

Rare Fungi

1) Geotrichum candidum2) Paecilomyces3) Paracoccidioides brasilensis4) Penicillim glaucum5) Penicillium citrinum6) Trichosporon

Rare Fungi

7) Fusarium8) Pseudallescheria boydii9) Cunninghamella10) Rhinosporidium seeberi11) Sporothrix schenckii

Summary:– The number of urinary tract infections

caused by fungi is increasing. Although the majority of fungal UTIs are caused by Candida species, physicians must maintain a high index of suspicion in order to identify the rare and environmental fungi that cause disease.

Summary: Many factors such as overuse of antibiotics,

immunosuppression , antifungal resistance and disseminated fungal infections predispose individuals to developing fungal UTI.

The astute physician must identify predisposing medical conditions and anatomical defects; then treat them accordingly.

Summary: Before beginning antifungal therapy first

obtain a U/A (rule out contamination).

Urine and blood cultures should be obtained in order to identify the organism and sensitivities.( This helps to prevent overuse of abx and avoids contrubuting to the increasing amount of resistance antifungal agents.)

Summary:

If obstruction or structural abnormalities are suspected then imaging of the urinary system is warranted.

If defects are visualized, only then should surgical management be employed.