Clinical decision support for the practicing hospitalist
by Karen Clarke, MD, MSc, MPH, FACP, and Behzad Razavi, MD, FACP, FIDSA
A previously healthy 74-year-old female was admitted to the ICU nine days ago for treatment of severe streptococcal pneumonia. Her initial urine culture, which was collected on hospital day one, showed no growth; however, Candida albicans was isolated from a urine culture collected seven days later. Her second urinalysis revealed mild pyuria. What is the appropriate evaluation and treatment of funguria?
Funguria is a relatively common clinical finding, and it is considerably more prevalent in patients with severe illnesses compared with healthy individuals. One study found that 2.2% of healthy, community-dwelling patients have Candida species (spp) in their urine.1 Candida spp are opportunistic organisms, which is implied by the fact that they can be isolated from 22% of patients admitted to an ICU.2
Despite the frequent isolation of Candida spp from urine cultures, the clinical significance is often unclear. It is difficult to determine if the funguria is caused by contamination, colonization, or a true urinary tract infection (UTI)—there is no test to reliably differentiate between these three possibilities. This is in contrast to bacterial UTIs, in which the findings of pyuria, bacteriuria, and a defined number of colony-forming units strongly support this diagnosis.3
Since it often is difficult to determine the true importance of funguria, its treatment has been controversial.3 The presence of a chronically indwelling urinary catheter often results in the funguria development, and, in many instances, simply removing the catheter will lead to its resolution.4 Furthermore, it has been demonstrated that for most patients with asymptomatic funguria, treatment with antifungal therapy has no effect on morbidity or mortality.5,6 Also, the propensity for funguria recurrence after completion of a course of antifungal therapy often discourages clinicians from ordering pharmacologic therapy.7,8
The prevalence of funguria is increasing worldwide, primarily due to the increased use of antibiotics and immunosuppressive therapy, as well as the more frequent utilization of invasive procedures.1,7 Candida spp cause as many as 30% of all nosocomial UTIs, and they are most commonly isolated from patients who require ICU treatment.9 In fact, in one large study, only 10.9% of 861 patients with funguria had no underlying illnesses.10
Common risk factors for funguria development include the use of urinary tract drainage devices, hyperalimentation, steroids, recent antibiotic therapy, diabetes mellitus, increased age, urinary tract abnormalities, female sex, malignancy, and a previous surgical procedure.1,2,3,7,10,11,12,13,14
By far, the most common cause of funguria is Candida spp. C. albicans is responsible for at least 50% of all cases of funguria.1,10 Other yeasts that cause funguria include C. glabrata (15.6%), C. tropicalis (7.9%), C. parapsilosis (4.1%), and C. krusei (1%).10
C. glabrata most often is isolated from individuals who have been treated with fluconazole, while C. parapsilos is seen most frequently in neonates. It is noteworthy that for approximately 10% of patients with candiduria, at least two types of Candida spp are isolated from the same urine culture.6,7,14 Other types of fungi that are infrequently isolated from the urine include Aspergillus, Cryptococcus, Fusarium, Trichosporon, and such dimorphic fungi as Histoplasma capsulatum and Coccidioides immitis.6 The latter organisms tend to cause funguria in individuals who have a disseminated fungal infection.
Although funguria is a relatively common finding in some patient populations, there is uncertainty about its importance. This is because funguria might be present for one of several reasons, and differentiating colonization from true infection is difficult. Unfortunately, there are no established criteria that reliably differentiate the two entities.3 Most patients with funguria have no symptoms suggestive of a UTI (e.g., dysuria, suprapubic tenderness, or hematuria).1,6,7,10
For bacterial UTIs, the presence of pyuria, and a defined minimum number of colony-forming units (CFUs), is helpful in establishing this diagnosis.1,2,3,6 However, with funguria, neither of these parameters is helpful in distinguishing between colonization, contamination, or a true UTI. The reason is that pyuria commonly develops as a result of either coexistent bacteriuria or local irritation caused by the presence of an indwelling urinary catheter.1,7 Large numbers of fungal CFUs might indicate colonization only, which has no clinical significance.6,14
Candida spp often live as saprophytes on the skin in the genital and perineal areas.13 Women have a 10% to 65% rate of colonization of the vulvovestibular area with Candida spp.7 This readily allows for contamination of urine specimens during the collection process, and facilitates the introduction of organisms into the urinary bladder, particularly through the use of indwelling urinary catheters.6
Colonization of indwelling urinary devices universally occurs, as long as they remain inserted for substantial periods of time.6 Funguria is commonly observed with the use of either urethral or suprapubic catheters.4,7 Fortunately, intermittent urinary catheterization rarely is associated with the development of funguria.15 Additional substrates for the development of colonization include ureteral stents and nephrostomy tubes.7,14
UTIs due to fungi can present in several ways, including asymptomatic funguria, lower-tract UTIs, upper-tract UTIs, and renal candidiasis.7 Asymptomatic funguria is most commonly found in hospitalized patients who have indwelling urinary catheterization devices. Fungal lower-tract UTIs (i.e., cystitis) resulting in symptoms are uncommon in both catheterized and noncatheterized patients.15 Fungal upper-tract UTIs, which usually manifest as pyelonephritis or sepsis due to a UTI, cannot be distinguished from those with a bacterial etiology because their clinical presentations are similar.7 Upper-tract UTIs tend to occur in patients who have either urinary obstruction or a disorder that results in urinary stasis.7 Fungal balls (bezoars) might develop as a serious complication of an upper UTI, and can result in obstruction. Renal candidiasis usually develops as a result of hematogenous dissemination of a fungal infection.7,14
Funguria generally does not predispose to the development of fungemia, but when it does occur, it usually is due to the presence of an upper-urinary-tract obstruction.3,4,6,8,12,14
It has been estimated that disseminated infection can be expected to occur in 1.3% to 10.5% of immunosuppressed patients with funguria.1,3,6,10,15
Until fairly recently, it was thought that renal transplant patients with funguria were at increased risk for developing fungemia, but this assertion is now known to be false.5
In deciding whether to treat funguria, it is important to consider the clinical setting in which it occurs. For example, when funguria occurs in asymptomatic patients with an indwelling urinary catheter, it often is due to colonization of the catheter. In such instances, simply removing the catheter will result in the resolution of between 33% and 40% of funguria cases.1,12 For most patients with asymptomatic funguria, it has been shown that the administration of antifungal therapy has no significant effect on morbidity or mortality.6,16
However, for certain patient populations who are at increased risk for developing a disseminated fungal infection, the treatment of asymptomatic funguria is indicated. This includes neutropenic patients, those with a known urologic obstruction, and those who will undergo a urologic procedure.7 It also is important to recognize that for oncology patients, or those with sepsis, funguria might be the only manifestation of a disseminated fungal infection.6
All patients with symptomatic funguria require treatment with antifungal therapy.6 Septic patients who have funguria require blood cultures and radiologic imaging studies; the latter are obtained in order to localize the anatomic source of infection, and also to evaluate for urinary obstruction.6 Such patients require the prompt administration of appropriate systemic antifungal therapy; failure to do so doubles the risk of in-hospital mortality.2
Fluconazole is the most utilized medication for funguria treatment. Unlike itraconazole, ketoconazole, and voriconazole, it achieves high concentrations in the urine.7,12 The efficacy of Capsofungin for the treatment of funguria has not been established firmly.14,17 Flucytosine has a limited role in the treatment of funguria, but it is very useful in the treatment of non-C. albicans species, which are increasing in frequency and often are resistant to fluconazole.6,14
Amphotericin B bladder irrigation no longer is recognized as a first-line treatment for candiduria, although some investigators still support its use, particularly in special circumstances.15 With the ready availability of an oral agent, IV amphotericin B is not commonly utilized for the treatment of asymptomatic funguria. However, either IV amphotericin B or IV fluconazole are options for the treatment of renal candidiasis.3,7 Unfortunately, the recurrence of funguria after the completion of an appropriate course of antifungal therapy commonly occurs.3,6,8,14,15
The patient’s initial blood and sputum cultures grew Streptococcus pneumoniae, which was adequately covered by the initial treatments of piperacillin/tazobactam and levofloxacin at the time of admission. Although the patient’s clinical condition improved gradually, she required ICU management throughout her hospital stay. Due to her poor mobility, an indwelling urinary catheter was inserted. The placement of this catheter, along with her age, sex, current antibiotic therapy, and debility, all increased her likelihood of developing funguria.
It is noteworthy that the patient had no suprapubic tenderness, and she had been afebrile for the preceeding 48 hours.
The finding of funguria in this patient should not create undue concern. The true source of her acute illness (Streptococcus pneumoniae) was identified. In this instance, there would be no expected benefit from the initiation of antifungal therapy. Instead, removal of the indwelling urinary drainage device would be advisable.
Asymptomatic funguria is a common clinical finding, one in which further workups or the administration of antifungal therapy is not necessary in most cases. Symptomatic funguria always requires treatment. TH
Dr. Clarke is a clinical instructor in the section of hospital medicine at Emory University Medical Center in Atlanta. Dr. Razavi is an assistant professor in the section of hospital medicine at Emory.
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