Confusion often accompanies a laboratory report indicating the presence of Candida or another yeast in the urine (funguria). The vexation that surrounds the detection of funguria is based on the knowledge that the finding may be either inconsequential or of great clinical importance. In fact, a urine culture demonstrating Candida can represent contamination, colonization, cystitis, pyelonephritis, or disseminated infection.
Fewer than 5% of all urine cultures will demonstrate the presence of funguria. However, among some groups of patients, funguria is a common finding; for example, candiduria has been detected in up to 25% of hospitalized nursing home residents who have indwelling bladder catheters and are receiving broad-spectrum antimicrobials. The majority of urine isolates are Candida species, usually C. albicans, C. tropicalis, C. parapsilosis, and on occasion C. (Torulopsis) glabrata; the latter microbe is a small, budding yeast that does not form hyphae or pseudohyphae and is capable of producing urinary tract infections in immunocompromised patients. Rarely, Cryptococcus neoformans, Blastomyces dermatitidis, Histoplasma capsulatum, or Coccidioides immitis will be isolated; the recovery of these fungi from urine always indicates the presence of serious disease, usually disseminated infection.
The first step in evaluation of the patient with a urine culture that reveals funguria is to repeat the test. Candida species are common colonizers of the perineum, and they are frequently associated with vulvovaginitis and balanitis, especially in diabetic patients; indeed, a positive finding on urine culture can be the first clue to the presence of diabetes mellitus. In any case, because a urine culture can become contaminated during collection, another sample should be obtained by a clean-catch technique; if necessary, the specimen can be secured by catheterizing the bladder (“straight cath spec”). If the subsequent sample is sterile and pyuria is absent, the initial result can be ignored; if candiduria is repeatedly demonstrated, attempts should be made to determine if the finding represents colonization or infection (i.e., cystitis, pyelonephritis, or disseminated candidiasis).
A simple method to distinguish urinary tract colonization from infection remains to be developed for Candida species. In the absence of an indwelling bladder catheter, some experts consider a colony count of greater than 10,000/mL to be important in distinguishing infection from colonization; others believe that any number of Candida organisms in a clean-catch urine specimen indicates infection. In the presence of a Foley catheter, large concentrations of yeast are commonly observed, but a role for specific colony counts in differentiating infection from colonization has not been established. Further, the presence or absence of pseudohyphae in the urine sediment is not useful in clarifying the problem. Serologic assays that detect candidal antigens do not yet have the sensitivity or specificity to identify invasive disease reliably.
Insight into the significance of candiduria will usually be gained if the clinician takes into consideration the circumstances in which the finding is made. Colonization of the bladder would be the diagnosis if the patient has risk factors for that problem (indwelling bladder catheter, diabetes mellitus, exposure to broad-spectrum antimicrobials, immunosuppressive therapy, pregnancy) but no symptoms (urgency, frequency, bladder discomfort), signs (suprapubic tenderness), or laboratory evidence (leukocytosis) of infection. Conversely, candidal cystitis would be a likely diagnosis if the patient has risk factors for colonization and clinical or laboratory evidence of locally invasive disease. Cystoscopy in patients with candidal cystitis typically reveals an inflamed mucosa studded with thrushlike plaques.
Candidal infection of the upper urinary tract (renal candidiasis) should be suspected if the patient has risk factors for colonization (indwelling bladder catheter, diabetes mellitus, exposure to broad-spectrum antimicrobials, female sex, immunosuppressive therapy) and symptoms (flank pain, nausea, vomiting), signs (fever, tachycardia, flank tenderness), and laboratory evidence (leukocytosis) of parenchymal disease. It must be emphasized, however, that in some patients, such as debilitated aged persons with diabetes mellitus, the usual clinical manifestations of pyelonephritis can be absent; clues to the presence of renal involvement in such patients include vague constitutional symptoms, a deterioration in kidney function, and persistence of candiduria despite topical antifungal therapy, such as bladder irrigation with amphotericin B. Upper urinary tract infection can be associated with the formation of fungal accretions (“fungus balls”), which can lead to ureteral obstruction and oliguria; thus, the laboratory evaluation may reveal azotemia. In the setting of obstruction by fungus balls, ultrasonography, computed tomography, or IV pyelography may demonstrate the presence of filling defects within the collecting system. Candidal pyelonephritis can also be associated with papillary necrosis. Finally, upper tract infection can lead to fungemia; patients with candidemia arising from the urinary tract usually have anatomic abnormalities causing obstruction and a history of invasive urologic procedures, such as surgery, stent placement, or nephrostomy tube insertion.
Up to 80% of patients with disseminated candidiasis have renal involvement as a complication of the fungemia. Because blood cultures are negative in 40% to 50% of patients with disseminated infection, candiduria can represent a very important clue to the presence of the life-threatening condition. Disseminated candidiasis should be suspected in the patient who has funguria and who has risk factors for blood-borne disease, including malignancy (leukemia, lymphoma), postoperative status, intravascular catheters, immunosuppressive therapy, prior broad-spectrum antimicrobial therapy, and protein-calorie malnutrition. The manifestations of disseminated candidiasis are broad, but most patients exhibit nonspecific symptoms leading to clinical deterioration. The diagnosis should also be considered in hospitalized patients with risk factors for disseminated candidiasis who exhibit enigmatic fever or experience sepsis with sterile blood cultures. Cutaneous lesions (red to pink nodules 0.5 to 1.0 cm in diameter) and retinal abnormalities (iritis, retinal exudates with or without extension into the vitreous) are uncommon but important findings in patients with the problem.
Patients who have candiduria as a consequence of colonization can usually be managed by eliminating the predisposing factor, such as withdrawing systemic antimicrobials, removing indwelling catheters, and treating uncontrolled diabetes mellitus; however, intravesicular or systemic antifungals are occasionally necessary. Symptomatic patients with candidal cystitis may also respond to maneuvers that eliminate risk factors, such as removal of an indwelling bladder catheter; however, if there is no response to removal of the catheter or if the latter is not feasible, antifungal therapy should be given. Fluconazole by mouth (200 mg followed by 100 mg daily for 4 to 7 days) represents one effective therapy. Alternatively, amphotericin B can be administered by continuous infusion through a triple-lumen catheter (25 to 50 mg in 1,000 mL of sterile water infused over 24 hours for 2 to 3 days). In selected circumstances, a single IV dose of amphotericin B (0.3 mg/kg) can be given.
Candidal pyelonephritis can result from ascending infection from the lower urinary tract or from hematogenous seeding in the setting of disseminated disease. Patients with primary renal candidiasis or disseminated infection require systemic antifungal therapy. Amphotericin B and fluconazole represent acceptable agents. The usual dose of amphotericin B is 0.4 to 0.6 mg/kg daily administered intravenously, to a total cumulative dose of 5 to 7 mg/kg; the dose of fluconazole is 400 mg given intravenously for 7 days followed by 400 mg by mouth for an additional 14 days. Of note, although fluconazole is active against the great majority of strains of C. albicans, the inhibitory activity of the agent against other candidal species is variable. (A.L.E.)
Ang BS, et al. Candidemia from a urinary tract source: microbiological aspects and clinical significance. Clin Infect Dis 1993;17:662.
In this retrospective review, the authors present 26 cases of candidemia that originated from the urinary tract. They note that 88% of the patients had structural abnormalities of the urinary tract, which often led to obstruction, and they report that 73% of the patients had undergone an invasive urologic procedure before the fungemia.
Bross J, et al. Risk factors for nosocomial candidemia: a case-control study in adults without leukemia. Am J Med 1989;87:614.
The administration of two or more antimicrobials or the presence of a central line, bladder catheter, azotemia, diarrhea, or candiduria were among the factors identified as placing nonleukemic adult patients at risk for candidemia.
Fisher JF, et al. Urinary infections due to Candida albicans. Rev Infect Dis 1982; 4:1107.
This article reviews the epidemiology, pathophysiology, and treatment of the problem and includes an algorithm useful in the management of patients with candiduria.
Fisher JF, et al. Efficacy of a single intravenous dose of amphotericin B in urinary tract infections caused by Candida. J Infect Dis 1987;156:685.
In this letter describing their experience with four diabetic patients who had chronic candiduria, the authors report that a single IV dose of amphotericin B (0.3 mg/kg) was usually effective in eliminating the fungus.
Fisher JF, Newman CL, Sobel JD. Yeast in the urine: solutions for a budding problem. Clin Infect Dis 1995;20:183.
Comprehensive review of the problem, with recommendations for therapy.
Fong IW, Cheng PC, Hinton NA. Fungicidal effect of amphotericin B in urine: in vitro study to assess feasibility of bladder washout for localization of site of candiduria. Antimicrob Agents Chemother 1991;11:7.
The authors describe a modified bladder washout technique for distinguishing candidal infection from colonization and for differentiating between invasive disease of the bladder and kidney.
Frangos DN, Nyberg LM Jr. Genitourinary fungal infections. South Med J 1986;79:455.
The authors review the spectrum of fungi capable of causing invasive disease of the urinary tract.
Hsu CCS, Ukleja B. Clearance of Candida colonizing the urinary bladder by a 2-day amphotericin B irrigation. Infection 1990;18:280.
In this study, 47 of 65 (72%) hospitalized nursing home patients with candiduria had the problem eradicated by a 2-day course of continuous irrigation with amphotericin B (1,000 mL of a 5% dextrose solution containing 50 mg amphotericin B infused during 24 hours).
Sanford JP. The enigma of candiduria: evolution of bladder irrigation with amphotericin B for management—from anecdote to dogma and a lesson from Machiavelli. Clin Infect Dis 1993;16:145.
The lack of a standard therapeutic approach to the patient with candiduria results from the absence of controlled clinical trials; however, rationales for the usual recommended therapies are presented.
Trinh T, et al. Continuous versus intermittent bladder irrigation of amphotericin B for the treatment of candiduria. J Urol 1995;154:2032.
In this prospective trial involving 20 patients with candiduria, the authors found that continuous irrigation was superior to intermittent instillation, with cure rates of 80% and 30%, respectively.
Wise GJ, Silver DA. Fungal infections of the genitourinary system. J Urol 1993; 149:1377.
An in-depth, well-referenced review of a wide range of mycotic infections of the genitourinary tract.