Candiduria – bystander or t(h)reat

One of the great pleasures of being an infectious disease specialist is that you are often confronted with basic questions that have very complicated and nuanced answers. Recently, I was called to give advice if treatment was indicated in the following case: a middle-aged man with chronic kidney diseases who had complaints of dysuria and an urinary sample positive for Candida glabrata. A good example of a simple question with a quite complicated answer.

What the guidelines say

For any question in medicine, guidelines always are a solid starting point. Both IDSA and ESCMID have published recommendations for treating candiduria, although the most recent ones date already back from 2016 (1,2). In general, both guidelines agree that candiduria in adults should only be treated if symptomatic, when an urologic procedure is planned or in the case of neutropenia. These recommendations haven’t changed the last 20 years and it might seem to you like what is the fuss about. However, treating infectious diseases are never that black and white. As hardly any studies exist in this matter, it is interesting to take a more detailed look at what evidence there is to come to a more nuanced answer.

In my opinion, there are four situations candiduria is often treated:              

              1. Symptomatic candiduria

              2. Neutropenic patients

              3. Urologic manipulation

              4. ICU patients

1. Symptomatic candiduria

Both guidelines agree that all patients with symptomatic Candida cystitis should be treated.

Before initiating treatment, there are some key facts you should consider:

• Symptomatic candida cystitis (defined as candiduria and lower urinary tract symptoms) is quite uncommon. In a prospective multicenter surveillance study of 861 patients, only 4% had such symptoms (3). This number is most likely itself an overestimation, considering the fact that 85% of patients had also a non-fungal infection.

  
  

• In the same study 83% had an indwelling urinary tract device (3). As a consequence, pyuria and the number of candida colonies become useless (5). This makes it even harder to distinguish true infection from colonization of the urinary tract.

• 25% to 30% of patients have co-existent bacteriuria, which is still a more likely source of infection (3).

• Catheter replacement can clear candiduria in 20% of the cases (4).

My viewpoint: How to manage ‘symptomatic candiduria’?

1. Exclude urinary tract obstruction by ultrasound. Combination of urinary tract obstruction and candiduria is definitively a reason to immediately start anti-fungal treatment (5).

2. Repeat the urine sample, preferably after changing the urinary catheter. Cystitis, however annoying it is, is not an emergency and candida is not part of the empiric for cystitis anyway. When the result of the urine sample comes back and is positive for a candida species, this should ideally be checked by a new sterile sample (also since a bacterial source remains quite likely).

3. If repeat urine sample turns out positive again for candida, treat with fluconazole (as long as Candida species is susceptible

2. Candiduria in neutropenia

Due to the fear of invasive candidemia and the associated mortality risk, both guidelines state that all neutropenic patients with candiduria should be treated (1,2) .

• As a reason, IDSA guidelines bring up that many physicians feel that candiduria indicates invasive candidiasis.

• Observational studies show a mixed picture although there is anecdotal evidence that candiduria precedes candidemia (6,7). Prophylactic treatment of candiduria in order to prevent invasive candidiasis hasn’t been tested in a trial however.

• The IDSA guidelines of 2016 refer to a small, retrospective study with 24 patients with hematologic malignancies and candiduria. In this study no association was seen between candiduria and candidemia (6).

• Neutropenia is a very heterogeneous condition; therefore not all patients have the same risk for invasive candidiasis. For instance, the risk is much lower in a patient undergoing chemotherapy and consequently becoming neutropenic for a few days than someone who is chronic neutropenic due to myelodysplasia.

My viewpoint: The threshold to treat candiduria in neutropenic patients should be low, although even here not all patients should probably be treated.

3. Candiduria in urologic manipulation

IDSA recommendation in case of asymptomatic candiduria:

Patients undergoing urologic procedures should be treated with oral fluconazole, 400 mg (6 mg/kg) daily, OR AmB deox- ycholate, 0.3–0.6 mg/kg daily, for several days before and after the procedure (strong recommendation; low-quality evidence).

• In the evidence summary of the IDSA guidelines, two articles are cited to support this claim. One reference is a case series in which two patients develop invasive candidiasis and candiduria after an urologic procedure although they had a negative urine sample beforehand. This is a situation in which IDSA doesn’t recommend to treat.

• In a best practice statement of 2019, the American Urological Association deviates from this recommendation, stating that a single-dose antifungal prophylaxis should be given in case of asymptomatic funguria in case of intermediate- and high-risk genitourinary procedures (9).

• A limited update of the European guidelines on urologic infections in 2024 doesn’t mention candida specifically but recommends antibiotic prophylaxis in the following situations (supported by often quite strong evidence) (8).

              - Ureteroscopy

              - Percutaneous nephrolithotomy

              - Transurethral resection of the prostate or bladder

              - Transrectal prostate biopsy

My viewpoint: Although there is definitively lack of data in case of candiduria and urologic manipulation, it seems quite logic to give a single-dose of fluconazole in the same indications when antibiotic prophylaxis is indicated if candiduria is present.

4. Candiduria in ICU patients

Probably this is the population with the highest incidence of candiduria due to their many risk factors (previous use of antibiotics, urinary catheter, immunosuppression)(5). Although asymptomatic candiduria is often treated in this population (10), there is pretty good evidence that this is not helpful (5). All guidelines also agree that asymptomatic candiduria shouldn’t be treated (1,2). Probably, by following the guidelines, 30 to 65% of anti-fungal treatment for candiduria can be avoided (10).

Note: fever is no sign of cystitis, especially when the patient has an urinary catheter. Candiduria should therefore not be treated in an ICU patient with fever, unless an ultrasound shows an obstruction in the urinary tract.

References:

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 Feb 15;62(4):e1-50.

2. Cornely OA, Bassetti M, Calandra T, et al; ESCMID Fungal Infection Study Group. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect. 2012 Dec;18 Suppl 7:19-37.

3. Kauffman CA, Vazquez JA, Sobel JD, et al. Prospective multicenter surveillance study of funguria in hospitalized patients. The National Institute for Allergy and Infectious Diseases (NIAID) Mycoses Study Group. Clin Infect Dis. 2000 Jan;30(1):14-8.

4. Sobel JD, Kauffman CA, McKinsey D, et al. Candiduria: a randomized, double-blind study of treatment with fluconazole and placebo. The National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group. Clin Infect Dis. 2000 Jan;30(1):19-24.

5. Hollenbach E. To treat or not to treat--critically ill patients with candiduria. Mycoses. 2008 Sep;51 Suppl 2:12-24.

6. Georgiadou SP, Tarrand J, Sipsas NV, Kontoyiannis DP. Candiduria in haematologic malignancy patients without a urinary catheter: nothing more than a frailty marker? Mycoses. 2013 May;56(3):311-4.

7. Candidemia: A Clinical and Molecular Analysis of Cases. Mycopathologia. 2017 Dec;182(11-12):1045-1052.

8. Kranz J, Bartoletti R, Bruyère F,et al. European Association of Urology Guidelines on Urological Infections: Summary of the 2024 Guidelines. Eur Urol. 2024 Jul;86(1):27-41.

9. Lightner DJ, Wymer K, Sanchez J et al: Best practice statement on urologic procedures and antimicrobial prophylaxis. J Urol 2020; 203: 351.

10. Jacobs DM, Dilworth TJ, Beyda ND, et al. Overtreatment of Asymptomatic Candiduria among Hospitalized Patients: a Multi-institutional Study. Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01464-17.