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Candiduria
Bushehr university of medical
sciences
Dr. Ghasemi
Pediatric nephrologist
Case
– A 34 –weeks preterm male , wt 1450 gr , NVD ,admit in NICU for
respiratory support
– During hospital course developed sepsis then AB changed as BC
sensitivity, also received TPN . Repeat BC after 2 wk showed C.albicans.
Pt had also rising in BUN , creat, and yeast cells in UA.
– Sono hyperechoic lesion in Lt renal pelvis with mild hydronephrosis
.1
‫ﻧﻭﺯﺍدﺍﻥ‬ ‫دﺭ‬ ‫ﮐﺎﻧدﻳدﻭﺭﻳﺎ‬ ‫ﻓﺎﮐﺗﻭﺭھﺎی‬ ‫ﺭﻳﺳﮏ‬
.2
‫ﺑﺭﺍی‬ ‫ﻣﻧﺎﺳﺏ‬ ‫ﮐﺷت‬ ‫ﻣﺣﻳط‬
‫ﻗﺎﺭچ‬
:
.3
‫ﺑﺭدﺍﺭی‬ ‫ﺗﺻﻭﻳﺭ‬ ‫دﺭ‬ ‫ﻗﺎﺭﭼﯽ‬ ‫ﻋﻔﻭﻧت‬ ‫ھﺎی‬ ‫ﻳﺎﻓﺗﻪ‬
.4
‫دﺭ‬ ‫ﺳﻭﻧﻭﮔﺭﺍﻓﯽ‬ ‫ھﺎی‬ ‫ﻳﺎﻓﺗﻪ‬
C.fungal ball
.5
‫ﺑﺎ‬ ‫ﺗﻭﺍﻧد‬ ‫ﻣﯽ‬ ‫ﮐﻪ‬ ‫ﺍدﺭﺍﺭی‬ ‫ھﺎی‬ ‫ﻳﺎﻓﺗﻪ‬
Yeast cell
‫ﮔﺭدد‬ ‫ﺍﺷﺗﺑﺎﻩ‬
‫ﮐﻭدﮐﺎﻥ‬ ‫ﻧﻔﺭﻭﻟﻭژی‬ ‫ﺍﻧﺟﻣﻥ‬ ‫ﺳﺎﻳت‬ ‫دﺭ‬ ‫ﻭﺑﻳﻧﺎﺭ‬ ‫ﺍﺳﻼﻳدھﺎی‬ ‫ﺑﻪ‬ ‫دﺳﺗﺭﺳﯽ‬ ‫ﻟﻳﻧﮏ‬
:
http://iranspn.com/?page_id=1284
Host defense mechanism
Flushing effect of urine
Nl urinary tract anatomy
Nl urinary tract function
Balanced distribution of perineal flora
Impairment of HDM : ( humoral , cellular ) , damage in
anatomical barrier ( skin maceration , burn , invasive surgery,
underlying disease that cause imbalance in the host defense )
High risk
DM
Catheterization , Stent
Depressed immune system
Prolonged hospital admission (ICU ) ,
prolonged AB therapy
Tumor
AIDS
Chemotherapy
Transplant
Female
Extreme of age
Intravascular catheter in high risk patient is the main source for
candidemia
In transplantation : multiple risk factor
(catheter/stent/antibiotic/obstruction/immune suppressive
therapy and leakage at anastomosis site ) can increased risk of
fungal infection
Candiduria classification :
Asymptomatic :
Healthy out-patient or healthy in patient
Symptomatic : UTI
Clinically unstable patient with candiduria
Candiduria maybe first clue for severe disease
Clinical Presentation
� Frequency , dysuria , urgency , suprapubic pain and hematuria are
common symptoms in cystitis
� Pneumaturia in emphysematous cystitis
� Decreased urination ,toxic condition
� Obstructive symptoms due to fungal ball
� Fever , vomiting
� Ascending infection to upper UT is rare but risk increased with DM
, obstruction , or anomalies of UT
Complications
� Emphysematous cystitis
� Emphysematous pyelonephritis
� Fungal ball (Bezoar)(candidoma) obstruction in upper and lower
urinary tract
� Intrarenal or perinephric abscess and papillary necrosis
� Decreased renal function
� Severe ARF is rare without obstruction ( postrenal )
Pathology fungal ball
Mycelia
Mucoid debris
Fragment from papillary necrosis
Lithiatic debris
Gas
Differential diagnosis
Hematoma
Urolithiasis
Tumor , TCC
Inflammatory debris
Fungal ball = Fungal bezoar
� Aggregation of fungal mycelium without invasion to around
tissue mostly in immune compromised patients
� Fungal ball :
� 1-Localized collection
� 2-cluster of pseudo mycelia large size
� In symptomatic candiduria/urosepsis with colicky abd
pain,obstructive problems,increased severity or
pyelonephritis,HTN,postrenal ARF
Diagnosis
U/A
U/C
Evidence of tissue reaction : cystitis – pyelonephritis
Diagnosis
Clinical lab gold standard for diagnosis is U/C
YLCC(yeast like cell count) in urine : good parameter for
(fungal detection in urine) candiduria and more CFU in urine
sample
YLCC>= 200 in 2 consecutive sample (at least)>= 100
Yeast cell particle : ovoid /spherical or elongated with power
400
pale green cells with smooth well defined wall homogenous
nucleus without organelles
Long period at the bench : aboundant pseudohyphae
yeast cast in renal involvement
Squamous epithelial cell in urine : unsuitable sample
Wbc,urothelial,epithelial,transitional cells
Diag …..
Fat droplet /erythrocyte/ca-oxalate crystals/acanthocyte and
deformed bacteria maybe mistake with yeast
Expert person with good quality microscope is needed for
correct diagnosis
Diag continue
Augmented cultures method: for unusual micro - organism
Candida may growth in BA or MacConkey agars
SDA method : select 98% of candida
PDA , CHROM agar , next generation sequencing (DNA sequencing
plat form)
100% sensitivity /97.3% specificity for fungal infect
PCR
Expanded(enhanced) quantitative urine culture
Repeat U/C : 10000 – 100000 (104-105) CFU/ml urine
Imaging
Sono : mobile/rounded heterogen hypoechoic mass
rarely hyperechoic or isoechoic with no evidence of
vascularity in mass by Doppler sono
Plain X-Ray : unremarkable/ unusual loculus of gas or
calcification within urinary system
Fluroscopy / cystography/pyelography: contrast filling
defect
CT : heterogenous soft tissue density without contrast
enhancement with region of gas or calcification rounded non
attached to the wall of UT thin rim of urine around the mass
CT urography : filling defect
MRI : identical to Ct scan
MRU : filling defect
Treatment
Anti fungal drugs :
Polyenes compounds ( AmB with different formulations )
Various azole derivatives (fluconazole-isavuconazole-
posaconazole-voriconazole)
Echinocandin (antidulafungin-caspofangin and micafungin)
flucytosine
Treatment
Fungal colonization of catheter not require treatment
Asymptomatic candiduria (rarely) should be treated in high risk pt:
Neutropenic pt
Neonate
Pt with renal allograft
Pt undergoing urologic manipulation
Increased risk for candidemia
ISDA recommendation
Asymptomatic
Elimination of predisposing factor
Treatment is not recommended unless in high risk for ICD
(neutropenic, VLBW infant<1500 gr , urologic manipulation)
that should be treated candidemia
Pt undergoing urologic procedure should be treated with oral
fluconazole 6mg/kg daily or AmB DC 0.3-0.6 mg/kg several
days before and after procedure
Contin……..
ICD in neonate: AmB DC : 1 mg/kg/d
Fluconazole : 12 mg/kg/d IV or oral
Lipid formulation AmB : 3-5 mg/kg/d
Echinocandins :should be used with caution
CSF examination? liver , GUT and spleen sono or CT
should be down if BC are persistently positive for Candida
CVC removal strongly suggested
Neutropenic pt
In neutropenic patient
Echinocandin (caspofungin ) loading dose 70 mg/m2 then 50 mg/m2
Micafungin 100 mg/day(2mg/kg) ,Anidulafungin loadinding dose
200 mg then 100 mg daily(2-1.5 mg/kg)
Lipid formulation: AmB 3-5 mg/kg/day
Fluconazole: 800 mg (12 mg/kg) loading dose then (6 mg/kg) 400
mg/day in pt who are not critically ill with no exposure to azole
antifungal drug
Cont……in neutropenic pt
Voriconazole: 6 mg /kg Q12h (400 mg) then 200-300 g(3-4
mg/kg)Q12h for 2 doses for additional mold coverage
C.krusei: echinocandin/lipid formulation AmB or voriconazole
is recommended
Minimum duration therapy for candidemia without metastatic
complication is 2 wk after clearance of candida from blood and
resolution of signs attributable to candidemia
Symptomatic cystitis
Fluconazole susceptible: oral fluconazole 3 mg/kg/day for 2 wks
Fluconazole-resistant C.glabrata AmB DC 0.3-0.6 mg/kg/day for 1-7 days or
oral flucytosine 25 mg/kg/dose Q6h for 7-10 days
C.Krusei recommendation is AmB DC 0.3-0.6 mg/kg/day for 1-7 days
Removal indwelling catheter
AmB DC bladder irrigation 50 mg/lit strill water for 5 days maybe usueful
for treatment of cystitis (fluconazole resistant species such as C.glabrata
C.krusei)
Pyelonephritis
Symptomatic ascending pyelonephritis :
For fluconazole sensitive: oral fluconazole 3-6 mg/kg/day for 2wks
Fluconazole resistant C. glabrata AmB DC o/3-0/6 mg/kg/day for 1-7
days with or without flucytosine 25mg/kg Q6h
C glabrata monotherapy with oral flucytosine (100mg/kg/d) for 2 wk
C krusei :AmB DC 0/3-0/6 mg/kg/d for 1-7 days
Elimination of urinary tract obstruction
Pt with nephrostomy tubes or stents in place, consider removal or
replacement
Corrected doses due to RFT and GFR
Bladder irrigation with amphotericin clear candiduria transiently
Recurrence despite successful systemic and local treatment may
occur
Micafungin sterile urine
Nephrostomy tube+irrigation by amphotericin B for short period
Candida UTI with fungal ball
Surgical intervention
Antifungal treatment (as cystitis or pyelonephritis)
Irrigation through nephrostomy tubes with
AmB DC 25-50 mg in 200-500 cc sterile water is
recommended
Take home message
Candiduria (UTI ) affects mostly patients who have UT obstruction
instrumentation/immune compromise patient
Antifungal drug therapy recommended only in pt will undergo
urologic procedure or in renal allograft transplantation
Generally candiduria is a benign condition that almost associated
with urinary instrumentation and may not warrant therapy
References
1. http://doi.org/10.2217/fmb.2019.0262 future medicine 2020
2. http://doi.org/10.2147/idr.S289885 2021
3. Candidemia from urinary tract source the challenge of candiduria
volume 46 ; 2018
4. Renal fungal ball BJR 2016:2(3)
5. Sanjay G/revankar wayne state university school of medicine
antifungal drugs 2021
6. Radio paedia.org July 19-23 2021
7. Diagnosis a new gold RUSH 2021
– 8.Candidal UTI diagnosis 2011
– 9.DOI:https//doi.org/10.3339/jkspn/.2019
– 10.Journal of fungi Jose Antonio 2020 dec
– 11. Urinary tract infections and candida albicans cent European J.Urol
2015: 68(1): 96-101
– 12. Doi: 10.3934/microbial .2020.017
– 13.doi:10.1007/s40272-o20-00379-2.
14.https://doi.org/10.1093/afid250.2021
15.https://doi.org/10.1016/jpurol.2021.07.022
16.Clinical practice guide line for management of candidiasis ISDA 2016
17.Practical guide line and atlas for diagnosis of fungal infection 2017
18.Candiduria a review article turk urol.2018 Nov,44(6):445-452
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Candiduria

  • 1. Candiduria Bushehr university of medical sciences Dr. Ghasemi Pediatric nephrologist
  • 2. Case – A 34 –weeks preterm male , wt 1450 gr , NVD ,admit in NICU for respiratory support – During hospital course developed sepsis then AB changed as BC sensitivity, also received TPN . Repeat BC after 2 wk showed C.albicans. Pt had also rising in BUN , creat, and yeast cells in UA. – Sono hyperechoic lesion in Lt renal pelvis with mild hydronephrosis
  • 3. .1 ‫ﻧﻭﺯﺍدﺍﻥ‬ ‫دﺭ‬ ‫ﮐﺎﻧدﻳدﻭﺭﻳﺎ‬ ‫ﻓﺎﮐﺗﻭﺭھﺎی‬ ‫ﺭﻳﺳﮏ‬ .2 ‫ﺑﺭﺍی‬ ‫ﻣﻧﺎﺳﺏ‬ ‫ﮐﺷت‬ ‫ﻣﺣﻳط‬ ‫ﻗﺎﺭچ‬ : .3 ‫ﺑﺭدﺍﺭی‬ ‫ﺗﺻﻭﻳﺭ‬ ‫دﺭ‬ ‫ﻗﺎﺭﭼﯽ‬ ‫ﻋﻔﻭﻧت‬ ‫ھﺎی‬ ‫ﻳﺎﻓﺗﻪ‬ .4 ‫دﺭ‬ ‫ﺳﻭﻧﻭﮔﺭﺍﻓﯽ‬ ‫ھﺎی‬ ‫ﻳﺎﻓﺗﻪ‬ C.fungal ball .5 ‫ﺑﺎ‬ ‫ﺗﻭﺍﻧد‬ ‫ﻣﯽ‬ ‫ﮐﻪ‬ ‫ﺍدﺭﺍﺭی‬ ‫ھﺎی‬ ‫ﻳﺎﻓﺗﻪ‬ Yeast cell ‫ﮔﺭدد‬ ‫ﺍﺷﺗﺑﺎﻩ‬ ‫ﮐﻭدﮐﺎﻥ‬ ‫ﻧﻔﺭﻭﻟﻭژی‬ ‫ﺍﻧﺟﻣﻥ‬ ‫ﺳﺎﻳت‬ ‫دﺭ‬ ‫ﻭﺑﻳﻧﺎﺭ‬ ‫ﺍﺳﻼﻳدھﺎی‬ ‫ﺑﻪ‬ ‫دﺳﺗﺭﺳﯽ‬ ‫ﻟﻳﻧﮏ‬ : http://iranspn.com/?page_id=1284
  • 4. Host defense mechanism Flushing effect of urine Nl urinary tract anatomy Nl urinary tract function Balanced distribution of perineal flora Impairment of HDM : ( humoral , cellular ) , damage in anatomical barrier ( skin maceration , burn , invasive surgery, underlying disease that cause imbalance in the host defense )
  • 5. High risk DM Catheterization , Stent Depressed immune system Prolonged hospital admission (ICU ) , prolonged AB therapy Tumor AIDS Chemotherapy Transplant Female Extreme of age
  • 6. Intravascular catheter in high risk patient is the main source for candidemia In transplantation : multiple risk factor (catheter/stent/antibiotic/obstruction/immune suppressive therapy and leakage at anastomosis site ) can increased risk of fungal infection
  • 7. Candiduria classification : Asymptomatic : Healthy out-patient or healthy in patient Symptomatic : UTI Clinically unstable patient with candiduria Candiduria maybe first clue for severe disease
  • 8. Clinical Presentation � Frequency , dysuria , urgency , suprapubic pain and hematuria are common symptoms in cystitis � Pneumaturia in emphysematous cystitis � Decreased urination ,toxic condition � Obstructive symptoms due to fungal ball � Fever , vomiting � Ascending infection to upper UT is rare but risk increased with DM , obstruction , or anomalies of UT
  • 9. Complications � Emphysematous cystitis � Emphysematous pyelonephritis � Fungal ball (Bezoar)(candidoma) obstruction in upper and lower urinary tract � Intrarenal or perinephric abscess and papillary necrosis � Decreased renal function � Severe ARF is rare without obstruction ( postrenal )
  • 10. Pathology fungal ball Mycelia Mucoid debris Fragment from papillary necrosis Lithiatic debris Gas Differential diagnosis Hematoma Urolithiasis Tumor , TCC Inflammatory debris
  • 11. Fungal ball = Fungal bezoar � Aggregation of fungal mycelium without invasion to around tissue mostly in immune compromised patients � Fungal ball : � 1-Localized collection � 2-cluster of pseudo mycelia large size � In symptomatic candiduria/urosepsis with colicky abd pain,obstructive problems,increased severity or pyelonephritis,HTN,postrenal ARF
  • 12. Diagnosis U/A U/C Evidence of tissue reaction : cystitis – pyelonephritis
  • 13. Diagnosis Clinical lab gold standard for diagnosis is U/C YLCC(yeast like cell count) in urine : good parameter for (fungal detection in urine) candiduria and more CFU in urine sample YLCC>= 200 in 2 consecutive sample (at least)>= 100
  • 14. Yeast cell particle : ovoid /spherical or elongated with power 400 pale green cells with smooth well defined wall homogenous nucleus without organelles Long period at the bench : aboundant pseudohyphae yeast cast in renal involvement Squamous epithelial cell in urine : unsuitable sample Wbc,urothelial,epithelial,transitional cells
  • 15. Diag ….. Fat droplet /erythrocyte/ca-oxalate crystals/acanthocyte and deformed bacteria maybe mistake with yeast Expert person with good quality microscope is needed for correct diagnosis
  • 16.
  • 17. Diag continue Augmented cultures method: for unusual micro - organism Candida may growth in BA or MacConkey agars SDA method : select 98% of candida PDA , CHROM agar , next generation sequencing (DNA sequencing plat form) 100% sensitivity /97.3% specificity for fungal infect PCR Expanded(enhanced) quantitative urine culture Repeat U/C : 10000 – 100000 (104-105) CFU/ml urine
  • 18.
  • 19. Imaging Sono : mobile/rounded heterogen hypoechoic mass rarely hyperechoic or isoechoic with no evidence of vascularity in mass by Doppler sono
  • 20.
  • 21. Plain X-Ray : unremarkable/ unusual loculus of gas or calcification within urinary system Fluroscopy / cystography/pyelography: contrast filling defect
  • 22.
  • 23.
  • 24. CT : heterogenous soft tissue density without contrast enhancement with region of gas or calcification rounded non attached to the wall of UT thin rim of urine around the mass CT urography : filling defect MRI : identical to Ct scan MRU : filling defect
  • 25.
  • 26.
  • 27. Treatment Anti fungal drugs : Polyenes compounds ( AmB with different formulations ) Various azole derivatives (fluconazole-isavuconazole- posaconazole-voriconazole) Echinocandin (antidulafungin-caspofangin and micafungin) flucytosine
  • 28. Treatment Fungal colonization of catheter not require treatment Asymptomatic candiduria (rarely) should be treated in high risk pt: Neutropenic pt Neonate Pt with renal allograft Pt undergoing urologic manipulation Increased risk for candidemia
  • 29. ISDA recommendation Asymptomatic Elimination of predisposing factor Treatment is not recommended unless in high risk for ICD (neutropenic, VLBW infant<1500 gr , urologic manipulation) that should be treated candidemia Pt undergoing urologic procedure should be treated with oral fluconazole 6mg/kg daily or AmB DC 0.3-0.6 mg/kg several days before and after procedure
  • 30. Contin…….. ICD in neonate: AmB DC : 1 mg/kg/d Fluconazole : 12 mg/kg/d IV or oral Lipid formulation AmB : 3-5 mg/kg/d Echinocandins :should be used with caution CSF examination? liver , GUT and spleen sono or CT should be down if BC are persistently positive for Candida CVC removal strongly suggested
  • 31. Neutropenic pt In neutropenic patient Echinocandin (caspofungin ) loading dose 70 mg/m2 then 50 mg/m2 Micafungin 100 mg/day(2mg/kg) ,Anidulafungin loadinding dose 200 mg then 100 mg daily(2-1.5 mg/kg) Lipid formulation: AmB 3-5 mg/kg/day Fluconazole: 800 mg (12 mg/kg) loading dose then (6 mg/kg) 400 mg/day in pt who are not critically ill with no exposure to azole antifungal drug
  • 32. Cont……in neutropenic pt Voriconazole: 6 mg /kg Q12h (400 mg) then 200-300 g(3-4 mg/kg)Q12h for 2 doses for additional mold coverage C.krusei: echinocandin/lipid formulation AmB or voriconazole is recommended Minimum duration therapy for candidemia without metastatic complication is 2 wk after clearance of candida from blood and resolution of signs attributable to candidemia
  • 33. Symptomatic cystitis Fluconazole susceptible: oral fluconazole 3 mg/kg/day for 2 wks Fluconazole-resistant C.glabrata AmB DC 0.3-0.6 mg/kg/day for 1-7 days or oral flucytosine 25 mg/kg/dose Q6h for 7-10 days C.Krusei recommendation is AmB DC 0.3-0.6 mg/kg/day for 1-7 days Removal indwelling catheter AmB DC bladder irrigation 50 mg/lit strill water for 5 days maybe usueful for treatment of cystitis (fluconazole resistant species such as C.glabrata C.krusei)
  • 34. Pyelonephritis Symptomatic ascending pyelonephritis : For fluconazole sensitive: oral fluconazole 3-6 mg/kg/day for 2wks Fluconazole resistant C. glabrata AmB DC o/3-0/6 mg/kg/day for 1-7 days with or without flucytosine 25mg/kg Q6h C glabrata monotherapy with oral flucytosine (100mg/kg/d) for 2 wk C krusei :AmB DC 0/3-0/6 mg/kg/d for 1-7 days Elimination of urinary tract obstruction Pt with nephrostomy tubes or stents in place, consider removal or replacement
  • 35. Corrected doses due to RFT and GFR Bladder irrigation with amphotericin clear candiduria transiently Recurrence despite successful systemic and local treatment may occur Micafungin sterile urine Nephrostomy tube+irrigation by amphotericin B for short period
  • 36. Candida UTI with fungal ball Surgical intervention Antifungal treatment (as cystitis or pyelonephritis) Irrigation through nephrostomy tubes with AmB DC 25-50 mg in 200-500 cc sterile water is recommended
  • 37.
  • 38.
  • 39. Take home message Candiduria (UTI ) affects mostly patients who have UT obstruction instrumentation/immune compromise patient Antifungal drug therapy recommended only in pt will undergo urologic procedure or in renal allograft transplantation Generally candiduria is a benign condition that almost associated with urinary instrumentation and may not warrant therapy
  • 40. References 1. http://doi.org/10.2217/fmb.2019.0262 future medicine 2020 2. http://doi.org/10.2147/idr.S289885 2021 3. Candidemia from urinary tract source the challenge of candiduria volume 46 ; 2018 4. Renal fungal ball BJR 2016:2(3) 5. Sanjay G/revankar wayne state university school of medicine antifungal drugs 2021 6. Radio paedia.org July 19-23 2021 7. Diagnosis a new gold RUSH 2021
  • 41. – 8.Candidal UTI diagnosis 2011 – 9.DOI:https//doi.org/10.3339/jkspn/.2019 – 10.Journal of fungi Jose Antonio 2020 dec – 11. Urinary tract infections and candida albicans cent European J.Urol 2015: 68(1): 96-101 – 12. Doi: 10.3934/microbial .2020.017 – 13.doi:10.1007/s40272-o20-00379-2.
  • 42. 14.https://doi.org/10.1093/afid250.2021 15.https://doi.org/10.1016/jpurol.2021.07.022 16.Clinical practice guide line for management of candidiasis ISDA 2016 17.Practical guide line and atlas for diagnosis of fungal infection 2017 18.Candiduria a review article turk urol.2018 Nov,44(6):445-452
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