Candida species are common members of the microbiota of the perineum but are found in urine in less than 1% of healthy persons.³,⁴ In hospitalized patients, especially those in the intensive care unit, candiduria is very common presumably because of the multitude of risk factors that allow ingress of organisms into the bladder and subsequent growth of Candida species in the urine.⁵,⁶,⁷,⁸,⁹,¹⁰,¹¹ A recent point prevalence survey of positive urine cultures obtained from hospitalized patients in hospitals throughout Europe found that Candida species were the third most common microorganism isolated from urine.⁵ Although it has been thought that candiduria could serve as a prelude to candidemia, this appears to be uncommon. Investigation of candiduric and candidemic isolates by molecular genotyping failed to show a relationship between the two sites in over half of the patients in one study.¹² In a large prospective surveillance study only 7 of 530 (1.3%) candiduric patients followed for 10 weeks developed candidemia.¹³

The risk factors for candiduria have been better defined than those for either bladder or kidney infection with Candida. This is due to the fact that firm diagnostic criteria for infection have not been defined, but candiduria is easily and simply defined as the growth of Candida species from a urine culture. Prospective surveillance studies and casecontrolled studies have shown that increased age, female sex, antibiotic use, urinary drainage devices, prior surgical procedures, and diabetes mellitus are important risk factors for candiduria⁶,⁸,¹¹,¹³ (Table 26.2).

In the largest multicenter surveillance study, which assessed 861 hospitalized patients, urinary drainage devices, consisting mostly of indwelling urethral catheters, were present in 83%, diabetes in 39%, and urinary tract abnormalities in 37% of patients who had candiduria. Only 11% of patients with candiduria had no obvious risk factor identified.¹³ In a multicenter study from Spain assessing candiduria in patients in an intensive care unit (ICU) setting, the independent risk factors associated with candiduria were age over 65 years, female sex, diabetes mellitus, prior antibiotics, mechanical ventilation, parenteral nutrition, and length of hospital stay before admission to the ICU.⁶

Among children, low-birth-weight neonates who are in an ICU are at the highest risk for candiduria and Candida urinary tract infections.¹⁴,¹⁵,¹⁶ Fewer data are available for patients in the community than for hospitalized patients. Risk factors appear to be similar to those in hospitalized patients and include diabetes, indwelling catheters, and the use of antibiotics.¹¹

Several studies, especially those focused on the ICU population, have noted increased mortality rates in patients who have candiduria when compared to similar patients without candiduria.⁶,⁹,¹³,¹⁷,¹⁸ In all of these studies it appeared that Candida urinary tract involvement was not responsible for death but was most likely a marker for seriously ill patients
who died of their underlying illnesses. Treatment of candiduria did not impact mortality rates.¹⁸

Candida species can cause renal infection by either the hematogenous or ascending routes. In contrast, most bacterial upper tract infections are related to ascending infection from the bladder. It is likely that most kidney involvement with Candida occurs by hematogenous seeding from a distant focus but almost all of these infections cause no urinary tract symptoms. Rather, the patient is ill from candidemia or other foci of infection due to Candida. The pathogenesis of hematogenous seeding of Candida to the kidney has been studied extensively in experimental rodents and rabbits given an intravenous bolus of C. albicans.¹⁹ Multiple microabscesses develop throughout the cortex. As the infection progresses, the yeasts penetrate through the glomeruli into the proximal tubules and are shed into the urine. Healthy animals eventually clear the organisms from the kidney, usually within 2 weeks; however, animals given immunosuppressive drugs cannot clear the infection. In agreement with experimental studies, renal microabscesses have been identified at autopsy in most patients who die of invasive candidiasis.

The pathogenesis of ascending infection with Candida has not been studied as extensively as that of hematogenous spread. Not surprisingly, it has been shown that those Candida strains found in the vagina are genetically related to the strains that cause candiduria in women who have indwelling bladder catheters while in the ICU.²⁰ There is no animal model that replicates the mode of spread that occurs in humans, which is presumably from the perineum into the bladder and then retrograde to the collecting system of the kidney.²¹ Creating the milieu in which Candida persist in the bladder has been difficult in experimental animals. Studies from the 1970s showed that rats made diabetic were unable to clear C. albicans inoculated into the bladder, and also that the presence of a concomitant Escherichia coli urinary tract infection allowed retrograde spread of Candida to the kidney.¹⁹ Unfortunately, these experiments have not been repeated nor has use of this model continued. Another model using bladder tissue explants from rabbits confirmed the essential role of adherence to the epithelial cells in colonization of the explants, but could not further explore the pathogenesis of retrograde spread.²²

C. albicans is the yeast most commonly isolated from urine, accounting for 50% to 70% of isolates. C. glabrata is the second most common yeast found in urine, accounting for about 20% of isolates.²,¹³ However, the proportion of urine isolates that are C. glabrata varies with different risk groups. Older adults frequently have C. glabrata isolated from urine, but neonates rarely are colonized or infected with C. glabrata. In patients who have hematologic malignancies, and in kidney transplant recipients, C. glabrata is more commonly isolated, possibly because of increased use of fluconazole in units that care for these patients. In one series of kidney transplant recipients, over half of all urine isolates were C. glabrata and only one third were C. albicans.²³ A study among hospitalized patients who had indwelling bladder catheters found that independent risk factors for C. glabrata candiduria were diabetes, ICU admission, and prior treatment with antibiotics and with fluconazole.²⁴

C. parapsilosis, C. tropicalis, and C. krusei are less commonly found in urine although some centers have reported C. tropicalis more often than C. glabrata.⁸ In general, there are no distinguishing characteristics of urinary tract infections due to the different Candida species.

Many laboratories do not identify yeast isolates to species level. This is reasonable because most yeasts that are
isolated are merely colonizing the urinary tract. However, knowledge of the species is needed if treatment of infection is required. Almost all isolates of C. albicans, C. tropicalis, and C. parapsilosis are susceptible to fluconazole, the antifungal agent of choice for treating Candida urinary tract infections. However, many isolates of C. glabrata and all isolates of C. krusei are resistant to fluconazole. Additional benefit is obtained when the laboratory performs susceptibility studies for fluconazole by helping the clinician to tailor therapy to the specific infecting organism.

Most patients with candiduria are asymptomatic, reflecting the fact that most do not have infection. In one large prospective surveillance study of patients with candiduria, fewer than 5% had symptoms suggestive of urinary tract infection.¹³ Patients who have had hematogenous spread to the renal parenchyma in the course of candidemia may have fever, hypotension, and other manifestations of sepsis associated with invasive candidiasis. They do not have symptoms suggesting urinary tract infection. In these patients candiduria is a clue to the presence of invasive candidiasis, but the urinary tract is not the primary site of infection or the source of candidemia.

In those patients who do have symptomatic urinary tract infection, symptoms are indistinguishable from those noted with bacterial infections. Cystitis is manifested by dysuria, frequency, urgency, and suprapubic discomfort. Rarely pneumaturia and the passage of particulate matter may be present. Fever is uncommon. Patients who have an indwelling bladder catheter rarely complain of symptoms other than suprapubic discomfort, and if they are in the ICU they often are unable to communicate about symptoms that they might have.

Patients who have pyelonephritis usually have chills, fever, and flank pain. Some patients are afebrile whereas others have predominantly lower tract symptoms, but upper tract infection is noted on imaging studies.²⁵ Pyelonephritis is more common in diabetics, women, and older adults. Complications of pyelonephritis are uncommon but include emphysematous pyelonephritis, perinephric abscess, and papillary necrosis—all of which are associated with increased morbidity and usually require surgical intervention.²⁶ Formation of a fungus ball composed of a mass of hyphae and yeast cells in the collecting system is frequently found with pyelonephritis and causes obstruction.²⁵,²⁷,²⁸,²⁹,³⁰ Neonates and infants are especially prone to develop fungus balls.²⁷,³⁰ If obstruction is present oliguria may occur and candidemia is common. Fungus balls can also form in the bladder and obstruct one or both ureters, causing hydronephrosis.²⁸