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Which Drugs Can Be Used To Treat Candida Urinary Tract Infection (UTI)?

 

Question

Which drugs can be used to treat Candida urinary tract infection (UTI)?

Answer

Yeasts are a major category of fungi and Candida sp. are one of the big categories of yeasts. The most common Candida sp. seen in clinical practice is C. albicans, but there are many other species. When a specimen in the microbiology lab is flagged as positive for a Candida sp. it can mean a variety of things. On one hand Candida sp. in a blood culture almost always requires treatment, since Candida should not be normally found in your bloodstream and blood culture contamination with yeasts is not very common. On the other hand, Candida sp. in a respiratory or urinary culture may often not require treatment, as Candida sp. colonize the GI tract and this can lead to culture contamination/ detection of colonization.

When a urine culture is positive for Candida sp., the clinician must investigate the circumstances that led to the Candida sp. recovery. This includes considering the likelihood of (a) urine culture contamination/ detection of colonization vs. (b) asymptomatic candiduria (i.e., Candida sp. in the urine in the absence of symptoms) vs. (c) lower Candida sp. UTI vs. (d) upper Candida sp. UTI (i.e., pyelonephritis). Clinicians must weigh the risks and benefits of prescribing an antifungal. Recognizing limitations of the available antifungal options is important when making this assessment. Actions such as removing indwelling catheters should also be considered, when applicable. 

As many as 80% of candiduria cases in hospitalized patients may be asymptomatic, for which treatment is usually inappropriate. Unnecessary treatment exposes patients to avoidable risks associated with antifungals which may include hepatotoxicity, drug-drug interaction, and arrhythmias. According to IDSA guidelines, high-risk patients may require treatment of asymptomatic candiduria. This includes neutropenic patients, very low-birth-weight infants (<1.5 kg), and patients who will undergo urologic manipulation.

As outlined in the IDSA candidiasis guidelines, a Candida sp. UTI can manifest in one of two ways: ascending or hematogenous spread. Most develop as an ascending infection with symptoms of cystitis or pyelonephritis. Hematogenous seeding from the blood to the kidneys is less common. 

Antifungals for urinary tract infection caused by Candida species
Potential Options Consider Avoiding
Fluconazole Azoles other than Fluconazole
Amphotericin (Conventional Formulation) Amphotericin (Lipid Formulations)
Flucytosine Echinocandins

Similar to managing drug-resistant UTIs caused by bacteria, there are limited antifungal drugs available to treat UTI caused by Candida sp. Existing options for fungal infections may also be subject to issues with drug resistance (e.g., Candida krusei is intrinsically resistant to fluconazole). Pharmacokinetics (i.e., drug excretion into the urine and renal tissues) must be observed when picking any drug for a UTI. Of antifungals, only fluconazole, amphotericin B deoxycholate and flucytosine concentrate well in the urinary tract. Per package inserts, the urinary concentrations of active drug for itraconzaole is <1%, voriconazole is <5%, posaconazole is <1%, and isavuconazole is <1%. While fluconazole is excreted in urine, the other azoles are hepatically excreted. Approximately 80% of fluconazole appears in the urine as unchanged drug. Per package inserts, the urinary concentrations of active drug for micafungin is not listed (but is primarily fecal), anidulafungin is <1%, caspofungin is <2%, and rezafungin is not listed (but is primarily fecal elimination or inactive metabolites in urine).  Lipid amphotericin B is listed as <1% and liposomal amphotericin B is listed as not studied. Since echinocandins and lipid-based formulations of amphotericin do NOT concentrate well in the urine / lack clinical data supporting their use, they should generally be avoided for Candida sp. UTI.

Interestingly, despite poor urinary concentrations obtained with echinocandins, it remains unknown how much antifungal needs to get to the urinary tract to have a successful outcome. Small retrospective studies have reported positive outcomes using echinocandins for Candida sp. UTI, but more data are needed to endorse this as a routine practice. We should also consider the type of UTI and the drug concentration at the site of infection, as low urine concentrations with reasonable tissue concentrations may allow use in certain circumstances.

The recovery of the Candida sp. in the urine should not be immediately dismissed nor always receive antifungal therapy. Assess for why Candida sp. appeared in the urine and correlate to the presence of symptoms before deciding on prescribing an antifungal. If there are no accompanying symptoms, most Candida sp. recovered in the urinary tract may reasonably be considered as a colonizer. Use guidelines and clinical judgement to help determine a reasonable course of action for each unique clinical scenario.

REFERENCES & READINGS

  1. Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1-e50. doi:10.1093/cid/civ933
  2. Jacobs DM, Dilworth TJ, Beyda ND, Casapao AM, Bowers DR. Overtreatment of Asymptomatic Candiduria among Hospitalized Patients: a Multi-institutional Study. Antimicrob Agents Chemother. 2017;62(1):e01464-17. Published 2017 Dec 21. doi:10.1128/AAC.01464-17
  3. Fischer JF, et al. Candida Urinary Tract Infections—Treatment. CID; 2011: S457-6. 
  4. Miceli MH et al. Isavuconazole: A New Broad-Spectrum Triazole Antifungal Agent. CID; 2015: 1558-1565.
  5. Gabardi S, Martin S, Sura M, Mohammed A, Golan Y. Micafungin treatment and eradication of candiduria among hospitalized patients. Int Urol Nephrol. 2016;48(11):1881-1885. doi:10.1007/s11255-016-1410-0
  6. Grau S, Luque S, Echeverría-Esnal D, et al. Urinary micafungin levels are sufficient to treat urinary tract infections caused by Candida spp. Int J Antimicrob Agents. 2016;48(2):212-214. doi:10.1016/j.ijantimicag.2016.05.010
  7. Sriskandan, S. (2010). Management of candiduria in the ICU. In Infectious diseases. (pp. 759–760). Mosby/Elsevier,. https://doi.org/10.1016/B978-0-323-04579-7.00232-X
  8. Sobel JD, LundstromT. Management of candiduria. Currently Urol Rep. 2001; 2(4): 321-5. 
  9. Augustin J, Raffalli J, Aguerro-Rosenfeld M, Wormser GP. Failure of a lipid amphotericin B preparation to eradicate candiduria: preliminary findings based on three cases, Clin Infect Dis, 1999, vol. 29: pg. 686-7.
  10. Sobel JD. When and how to treat candiduria, Infect Dis Clin Pract, 2006, vol. 14 (pg. 125-6).
  11. Felton T, et al. Tissue Penetration of Antifungal Agents. CMR. 2014.

ANSWERED BY

Hunter O. Rondeau, Pharm.D. & Timothy P. Gauthier, Pharm.D., BCPS, BCIDP – December 2023

Q&A DISCLAIMER

The ID PharmD Q&A pages attempt to answer common pharmacy questions by providing the perspective and opinion of a trained expert with knowledge relevant to the question. That noted, these answers are not provided as all-inclusive comprehensive responses. This is not provided for direct patient care purposes.

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