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(1/12) Where is fluconazole resistant yeast MOST difficult to treat?
(2/12) While each present unique issues 
Fluconazole resistant fungal urinary tract infections (UTI) are particularly challenging. The rationale will require an adventure into antifungal PK…
Fluconazole resistant fungal urinary tract infections (UTI) are particularly challenging. The rationale will require an adventure into antifungal PK…
(3/12) Let’s start with the basics 
Most fungal UTIs are caused by C. albicans & other Candida spp.
Yeast in urine usually non-pathogenic.
How do you know if it is pathogenic? ✓ for predisposing factors &
for symptoms.
https://pubmed.ncbi.nlm.nih.gov/21498839/
Most fungal UTIs are caused by C. albicans & other Candida spp.Yeast in urine usually
non-pathogenic. How do you know if it is pathogenic? ✓ for predisposing factors &
for symptoms. https://pubmed.ncbi.nlm.nih.gov/21498839/
(4/12) Symptomatic treat! Due to the PK profile, fluconazole = Candida spp. cystitis DOC if susceptible.
☟study: Fluconazole ↑↑ [tissue]/[plasma] ratio, Fluconazole [urine] >> [plasma]x 10!
https://pubmed.ncbi.nlm.nih.gov/2543281/
![(4/12) Symptomatic treat! Due to the PK profile, fluconazole = Candida spp. cystitis DOC if susceptible. ☟study: Fluconazole ↑↑ [tissue]/[plasma] ratio, Fluconazole [urine] >> [plasma]x 10! https://pubmed.ncbi.nlm.nih.gov/2543281/](https://pbs.twimg.com/media/Eow6A9UW8AYIRAI.png "(4/12) Symptomatic treat! Due to the PK profile, fluconazole = Candida spp. cystitis DOC if susceptible. ☟study: Fluconazole ↑↑ [tissue]/[plasma] ratio, Fluconazole [urine] >> [plasma]x 10! https://pubmed.ncbi.nlm.nih.gov/2543281/")
treat! Due to the PK profile, fluconazole = Candida spp. cystitis DOC if susceptible. ☟study: Fluconazole ↑↑ [tissue]/[plasma] ratio, Fluconazole [urine] >> [plasma]x 10!
https://pubmed.ncbi.nlm.nih.gov/2543281/
(5/12) So what if fluconazole is resistant?
For most infections with C. glabrata or kruseiitra, vori, and posa; BUT, these are 
suitable for cystitis!
For most infections with C. glabrata or krusei
itra, vori, and posa; BUT, these are suitable for cystitis!
(6/12) Let’s review urinary penetration of different antifungals. 
Only flucytosine and IV AmB are widely accepted to have adequate urinary penetration ☟
https://academic.oup.com/cid/article/43/Supplement_1/S28/318707
Only flucytosine and IV AmB are widely accepted to have adequate urinary penetration ☟https://academic.oup.com/cid/article/43/Supplement_1/S28/318707
(7/12) What about Echinocandins? Despite minimal urinary penetration Case reports have demonstrated successful
TX of Candida UTIs w/ mica & caspo… though the use of these agents for cystitis is 
routinely recommended and more evidence is needed 
https://dig.pharmacy.uic.edu/faqs/2019-2/august-2019-faqs/is-there-evidence-to-support-the-use-of-echinocandins-for-urinary-tract-infection/
Case reports have demonstrated successful TX of Candida UTIs w/ mica & caspo… though the use of these agents for cystitis is routinely recommended and more evidence is needed https://dig.pharmacy.uic.edu/faqs/2019-2/august-2019-faqs/is-there-evidence-to-support-the-use-of-echinocandins-for-urinary-tract-infection/
(8/12) Does the formulation of AmB matter? YES!
Lipid AmB << AmB deoxy for nephrotoxicity/infusion rxns but literature suggests liposomal has poor [kidney/urine] penetration… AND… Candida UTI treatment failure with liposomal AmB is reported.
https://pubmed.ncbi.nlm.nih.gov/10530471/
![(8/12) Does the formulation of AmB matter? YES! Lipid AmB << AmB deoxy for nephrotoxicity/infusion rxns but literature suggests liposomal has poor [kidney/urine] penetration… AND… Candida UTI treatment failure with liposomal AmB is reported. https://pubmed.ncbi.nlm.nih.gov/10530471/](https://pbs.twimg.com/media/Eow67kgXYAAFw9y.png "(8/12) Does the formulation of AmB matter? YES! Lipid AmB << AmB deoxy for nephrotoxicity/infusion rxns but literature suggests liposomal has poor [kidney/urine] penetration… AND… Candida UTI treatment failure with liposomal AmB is reported. https://pubmed.ncbi.nlm.nih.gov/10530471/")
Lipid AmB << AmB deoxy for nephrotoxicity/infusion rxns but literature suggests liposomal has poor [kidney/urine] penetration… AND… Candida UTI treatment failure with liposomal AmB is reported.
https://pubmed.ncbi.nlm.nih.gov/10530471/
(9/12) Don’t forget about flucytosine! Not generally our first thought… but a viable option in some Candida cystitis.
Resistance develops quickly with monotherapy so TX for 7-10d only. Renally dosed and for hepatotoxicity 
Resistance develops quickly with monotherapy so TX for 7-10d only. Renally dosed and
for hepatotoxicity
(10/12) Looking for non-standard routes of admin? AmB deoxy can be administered as a bladder irrigation 
Irrigations can be done continuously [50mg/L] for 5-7d and may resolve Candida cystitis in > 90% of patients, however… relapse rates are high! https://pubmed.ncbi.nlm.nih.gov/7109077/
Irrigations can be done continuously [50mg/L] for 5-7d and may resolve Candida cystitis in > 90% of patients, however…
relapse rates are high! https://pubmed.ncbi.nlm.nih.gov/7109077/
(11/12) Short courses of IV AmB deoxy can be considered for cystitis. In fact, single doses of AmB deoxy have produced fungicidal concentrations in urine for days-weeks after x1 IV dose! 
This graph shows AmB urine conc. following x1 IV dose in 3 patients.
This graph shows AmB urine conc. following x1 IV dose in 3 patients.
(12/12)
So… let’s recap!
Fluconazole is DOC in susceptible Candida spp. UTIs
Flucytosine & AmB are 1st line options w/strong evidence for fluconazole R isolates
AmB formulation matters & don't forget to monitor for ADRs!
Echinocandin PK is 
and evidence is limited
So… let’s recap!
Fluconazole is DOC in susceptible Candida spp. UTIsFlucytosine & AmB are 1st line options w/strong evidence for fluconazole R isolatesAmB formulation matters & don't forget to monitor for ADRs!Echinocandin PK is and evidence is limited
