Fungal Urinary Tract Infections Diagnosis and Management

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Fungal Urinary Tract Infections Diagnosis and
Management

• Tristan T. Berry, M4
• Medical College of Virginia

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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

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History

• 1890 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.

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Epidemiology and Predisposing Factors
Fungal pathogens are the cause of increasing
nosocomial infections in hospital communities.

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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.

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Epidemiology and Predisposing Factors
Three distinct groups of pathogens are noted
for causing fungal UTIs

• 1) Opportunistic organisms
• 2) Environmental
• 3) Rare and unusual

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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.

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Environmental

• include Blastomyces, Histoplasmosis, Coccidoides.
  
• found primarily in soil,environment and guano.
  inhabit human flora or environment.

Rare and unusual

• Mucormycosis and others

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Opportunistic Fungi
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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.

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C. Albicans
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Pathogenesis

• Most common opportunistic fungi.
• Causes thrush, vaginitis, chronic mucocutaneous
  candidiasis
• When local or systemic host defenses are
  impaired, disease may result.

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Pathogenesis

• may disseminate to multiple organs esp. in IVDA
  and right sided endocarditis.
• kidney is the most commonly involved organ with
  systemic fungal infection. gt85
• Accounts for 6.9 of nosocomial infections

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Pathogenesis

• Candida Spp are the most common organisms causing
  fungal UTI.
• Candida albicans accounts for 74
• Glabrata 8
• Parapsolosis7
• Tropicalis 3

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Predisposing Conditions

• 1) Diabetes (impaired phagocytic and fungacidal
  function of neutrophils)
• 2) Protracted course of antibiotics

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Predisposing Conditions

• 4) Neoplasm
• 5) Oral contraceptives
• 6) Elderly Population
• 7) Infants- due to immature T-Cell defense
• 8) Chronic indwelling catheter

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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.

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Diagnostic Features

• microscopic urine studies
• urine culture can be helpful for species
  identification and sensitivities
• Urine colony counts (significant if gt105 without
  indwelling urinary catheter)

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Simple vs. Complex UTI
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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

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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.
  

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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.

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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

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Imaging

• U/S, Excretory urography,
• Retro pyelogram
• CT
• Renal Scintigraphy
• Imaging studies typically exhibit filling
• defects of the urinary system

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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

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CASE

• HPI56 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 txd
  with abx.

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CASE

• Exam- pt. was febrile appeared acutely ill.
• Dry mucous membranes
• Diffusely tender abdomen
• Bilateral CVAT
• LABS
• Leu 25x109 with 82 pmns
• BUN 82, Creat 7.9 Glu 280

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CASE

• U/A Numerous leukocytes per hpf
• Many yeast forms.
• Pt was initially treated with Ampicillin and
  Ciprofloxacin. IVF and IV insulin.
• Symptoms persisted.

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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.

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CASE

• Urine culture- C.Tropicalis 104 - 105
• 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.

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CASE

• Therapy cont.for 3 weeks until U/C were negative.
• Dcd with Creatinine of 2.1mg/dL.
• No evidence of hydronephrosis at 6 month follow
  up.

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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.

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Cryptococosis

• Predisposition HIV, DM, lymphoma, ETOH abuse
• GU involvement
• Adrenal-infarction
• Renal- pyelonephritis,abscess
• Prostate- bladder outlet obstruction or
  prostatitis
• Penis- ulcers of glans

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Cryptococosis

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

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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.

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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
• DXIsolation from urine,semen or tissue.

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Apergillosis-Treatment

• Systemic Amphotericin B for 3 months
  Kidney-Percutaneous aspiration, nephrostomy J-
  stents
• Very little data to support use of itraconazole

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Environmental Fungi
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Coccidioidomycosis

• Organism Coccidioides immitus
• Propertiesdimorphic 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

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Coccidioidomycosis

• Clinical manifestations mild influenza or flu
  like illness Valley fever.
• Predisposition Age gt65 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

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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

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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.

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Histoplasmosis

• Majority of involvement is spleen and liver.
  Pulmonary involvement results in cavitary
  lesions.
• Clinical manifestations pneumonia
• Predisposition HIV, transplant pts children.

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Histoplasmosis

• GU involvement
• Kidneys- noncaseating granulomas,cutaneous
  fistulas.
• Adrenal-Addisons dz- will require hormone
  replacement.
• Prostate- Abscesses

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Histoplasmosis

• Dx- Identification of organism in urine,semen or
  tissue. Culture or skin test.
• Tx- IV Amphotericin B(gt2g) total dose followed by
  long term Itraconazole 200mg/d x12 wks
• Surgical management- Surgical excision or
  drainage of prostate abscess.

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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.

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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

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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

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Rare Fungi
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Mucormycosis

• Organism- Mucor
• Properties-mold
• Epidemiology-widely in nature
• Transmission- Inhalation of airborne spores
• Predisposition- DKA,AIDS, liver abnormalities

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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 gt1gram for 1 month

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Rare Fungi

• Geotrichum candidum
• Paecilomyces
• Paracoccidioides brasilensis
• Penicillim glaucum
• Penicillium citrinum
• Trichosporon

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Rare Fungi

• 7) Fusarium
• 8) Pseudallescheria boydii
• 9) Cunninghamella
• 10) Rhinosporidium seeberi
• 11) Sporothrix schenckii

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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.

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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.

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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.)

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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.