Overview
Candiduria refers to the presence of Candida spp. in the urine. This finding is for the most part a benign process associated with the use of urinary catheters and antimicrobial therapy [1171]. Nevertheless, candiduria may be one of the most challenging of the candidal infections. The challenge comes from the fact that finding Candida spp. in the urine can be either completely insignificant (e.g., due to contamination or asymptomatic colonization) or be a marker of a very serious entity such as invasive renal parenchymal disease related to disseminated candidiasis or postlaparotomy peritonitis [224, 1171, 1602, 2448]. In between these two extremes are other important clinical possibilities (e.g., candidal cystitis and fungus balls) that also require specific treatment.
Causes of Candiduria
| Category | Condition | Comments |
|---|---|---|
| Benign | Contamination |
|
| Insignificant Candiduria |
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| Urinary Tract-Related | Urethritis |
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| Cystitis |
|
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| Prostatitis |
|
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| Fungus ball formation (bladder, renal pelvis) |
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| Upper urinary tract candidiasis due to ascending infection |
|
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| Hematogenous Candidiasis with Renal Involvement | Upper urinary tract candidiasis as part of the syndrome of Acute Disseminated Candidiasis |
|
Epidemiology
The overwhelming majority of patients with candiduria suffer a completely benign process. Indeed, the largest study ever published on funguria found that only seven patients (1.3%) had documented candidemia among 861 consecutive patients with candiduria [1171]. However, funguria is sometimes a marker of disseminated candidiasis [1602, 1621]. Approximately 10% of cases of candidemia are related to a urinary tract source [77, 1904]. In one study of 104 patients with funguria, ten percent were diagnosed with candidemia either simultaneously or within a few days of the detection of the funguria. Importantly, one-third of these cases had obstructions in the urinary tract. The other two-thirds had classic risk factors for invasive candidiasis [2175]. This study appears to be unusual, as most other studies have found that candiduria is a benign finding [1171, 1933, 2125, 2455].
Risk Factors for Candiduria
| Risk Factor | Reference |
|---|---|
| Age: Elderly | [1108, 1171, 1933] |
| Sex: Women and girls (vaginal colonization) | [859, 1171] |
| Condition: Pregnancy | [1637, 2301] |
| Diseases: |  |
| Diabetes Mellitus | [1171, 1933]] |
| Urinary Tract diseases producing obstruction | |
|
[1696] |
| Malignancies | [77] |
| Procedures | |
| Urinary tract catheterization | [77, 859, 1171] |
| Stenting | [77] |
| Insertion of nephrostomy tubes | [77] |
| Major urinary tract surgeries | [77] |
| Extracorporeal lithotripsy | [1692] |
| Surgical procedures | [1171] |
| Antibiotic exposure | [859, 1171] |
Most cases of candiduria occur in patients that are or have been recently catheterized. The other two most important risk factors are diabetes mellitus and age [1108, 1171].
Candiduria and Candida species
Candida albicans causes ~50% of cases of Candiduria [2125, 2448] Candida glabrata has been consistently responsible for ~25% of cases of candiduria [2125, 2174]. Candida tropicalis is the third most common agent. Around 5% of patients with candiduria will have 2 or more species simultaneously [1171].
Clinical Manifestations
Clinical manifestations are of little help for physicians dealing with funguria. Symptoms like dysuria, frequency and urgency were presented only in 2-4% of patients with candiduria studied by Kauffman et al. [1171]. Patients with urethritis and cystitis, if symptomatic, will present with the same symptomatology as is seen with a bacterial urinary tract infection. However, catheterized patients rarely have these complaints. And, when they do, it is not possible to decide if the symptoms are caused by the catheter itself or are related to lower urinary tract infection.
Even patients with potentially significant candiduria are usually asymptomatic. Further confusing the situation, many patients with candiduria and fever have indeed quite convincing conditions that explain their hyperthermia (e.g., pneumonia, bacteremia, bacterial urinary tract infection) [713].
The one notable exception is that candiduria in the presence of a fungus ball of the urinary collecting system should be taken quite seriously due to the possiblity of urinary obstruction (see Fungus ball in the urinary tract”).
Specific Diagnostic Strategies
Unlike bacteriuria and bacterial urinary tract infections, neither microbiological quantification of Candida colonies or the concomitant presence of pyuria are good guides to identify disease and rule out colonization. It has been said that finding mixed yeast and cellular (red and/or white cells) casts could help in identifying cases of renal candidiasis, but the frequency of this finding is unknown [116, 901, 1625].
The difficulty of interpreting correctly a case of candiduria occurs mostly in the hospital setting. By itself, the presence of an indwelling urethral catheter may permit growth on the surface of the catheter of sufficient fungus to raise the urinary colony counts to a level that is exactly that seen in cases with renal candidiasis [859, 2448].
Further, patients with true disseminated candidiasis can have variable colony counts. In a study of 39 cases of disseminated candidiasis, 38% of them had candiduria. However in 2/3 of these cases the colony count was less than 104/ml. As a further demonstration of this problem, an animal model has shown that rabbits affected with renal candidiasis may have a negative urine culture [1626]. Therefore, clear cut rules that distinguish infection from asymptomatic colonization are lacking.
Considering all that has been discussed above, it should not be surprising that current knowledge of candiduria does not allow a clear differentiation between patients infected from those who are not. Instead, a systematic approach should be followed when dealing with a patient with candiduria.
A Systematic Approach to the Urine Culture Positive for Candida spp.
- Repeat the urine culture – Ensure that the sample is adequately collected! If patient is not catheterized, use the clean-catch method. If the patient is already catheterized, change catheter and take new sample within 30 minutes.
- If the urine culture is persistently positive – Consider the possibility that the patient has Invasive Candidiasis by looking for these risk factors and symptoms:
- Neutropenia,
- Fever of unknown origin,
- Use of broad spectrum antibiotics,
- Central venous catheter in place,
- Receiving hyperalimentation,
- Recent surgery, especially abdominal surgery,
- Colonization with Candida spp. in other sites (wound, peritoneum).
- If one or more of these conditions are present – Obtain blood cultures to look for candidemia. See also our discussion of diagnostic strategies for Invasive Candidiasis. Empirical therapy may be warranted.
- If patient is diabetic or has a history of urinary tract obstruction or recurrent UTI – Rule out fungus ball and pyelonephritis by use of suitable imaging studies, Check the urinary sediment for mixed yeast and cellular casts.
- If patient is catheterized – Reduce the time of urine catheterization to the minimum possible.
Therapies
Treatments for Candiduria
| Drugs | Route | Dosage |
|---|---|---|
| Fluconazole | Oral or Intravenous | 400 mg loading dose, then 200 mg/day for 14 days. Therapy can be PO unless the patient is unable to take oral therapies. |
| Amphotericin B | Bladder Irrigation or Intravenously | Bladder irrigation is classically performed by irrigating with a solution of fifty mg amphotericin B in 1 liter of sterile water over a a 24-48 h period. Intravenous therapy is appropriate for cases of invasive candidiasis. |
As there are no clear data that allow a clean stratification of patients with candiduria, we still cannot predict who will benefit from eradicating Candida from their urinary tract from those who will not. And, even apparently successful therapy is often followed by recurrence unless all of the predisposing factors are eliminated [2125].
Sobel et al. randomized 316 patients with asymptomatic candiduria to receive fluconazole or placebo for 14 days [2125]. The efficacy of fluconazole to erradicate Candida from the urine was clearly demonstrated (50% vs. 29%, p > 0.0001), however, response was notably higher among patients that had the indewelling catheter removed (78%). The most surprising and disappointing finding of this study was the high rate of relapse (about 60%).
Many cases of candiduria resolve spontaneously. Rates of clearance ranging from 28 to 75% have been reported [1171, 2056, 2455]. In catheterized patients, ~40% of cases will resolve with catheter removal [2125]. If chronic catheterization is required, changing the catheter will resolve 20 to 30% of cases. [713, 2125].
Bladder irrigation with amphotericin B is a time-honored therapy of unknown value. Relapse or recurrence occurs in between 20 to 40% of cases treated with amphotericin B bladder irrigation treatments [713, 1074, 2449]. Some authors recommend periodic clamping of the catheter, instead of continuous irrigation, but there is no data supporting the superiority of any one approach. [1075, 2024].
In conclusion, resolution of candiduria is accomplished in about 50% of cases using any of these treatment modalities. Failure rates seem to be higher among patients with diabetes [1171]. Relapses are particularly frequent among patients who remain catheterized [2125].
Difficult Clinical Situations
Candiduria in the apparently well patient
Urinary fungus ball