Figure. Management of fungiuria. Fungiuria in most healthy, immunocompetent individuals is of minimal clinical significance and likely to resolve spontaneously. In those with predisposing risk factors, treatment should attempt to resolve what factors can be reasonably addressed. In high-risk individuals and those in whom atypical fungal pathogens are identified, infectious disease consultation may be appropriate. GU indicates genitourinary; IV, intravenous; QID, 4 times daily. Data were derived from Pappas et al.²

In the past 10 years, we have faced the realization that humans host a “microbiome”—abundant, polymicrobial communities that exist on body surfaces and in viscera. In a healthy state, these communities are diverse, environment-specific, and carefully balanced, serving an important role in maintaining organ homeostasis.¹ But in the urinary tract, as in other organ systems, the microbiome is not just bacteria, it is an ecosystem of interacting microbes, including fungi. Yet our dogma is still that the presence of urinary fungi is pathologic—an abnormal “infection” that places individuals at risk of complications. But now that we understand that urinary fungi are physiologic, what do we really know about fungal infections of the urinary tract?

There are 2 mechanisms by which fungi can infect the urinary tract; one is as a result of ascending infection, in which infections begin in the bladder and ascend to the kidney, and the other is via hematogenous dissemination to the kidneys. Interestingly, at least in animal models, the kidneys are the most susceptible of all organs to hematogenous spread. Distinguishing between these clinical scenarios can be challenging. The vast majority of fungal infections of the kidney and bladder involve Candida albicans or other Candida species. While a variety of other fungi have been reported as genitourinary pathogens, typically these reports involve the kidneys as a result of disseminated infection from other sites.

How are fungal infections managed? The Infectious Disease Society of America has comprehensive guidelines on the treatment of fungal infections,² the pharmacologic management of which is simplified here (see Figure). If there is no fungiuria, there should be no treatment. If the culture demonstrates atypical fungi (any non-Candida species), it is wise to consult an infectious disease colleague. For Candidal infections, the mainstay of treatment is fluconazole, but as Candida can rapidly develop resistance to fluconazole, obtaining fungal susceptibilities is recommended to ensure early recognition of azole resistance and appropriate tailoring of antifungals. Nonazole antifungals have significant side effects and require intensive monitoring, so it is wise to involve physicians with experience prescribing these medications. These challenges and side effects have prompted attempts to manage fungiuria with intravesical amphotericin. However, fungiuria usually recurs immediately upon discontinuation of treatment.

These treatment pathways are helpful if the treating physician has a high suspicion for a urinary fungal infection confirmed by culture. But it is not always clear when to suspect urinary fungi as the causative agent in a patient’s illness. As with urinary bacteria, detection of urinary fungi does not necessarily mean infection. It is much more commonly a sign of colonization; the challenge is in knowing when to treat and who is at risk for more serious complications.

Instinctively, we worry about fungiuria causing ascending infection, fungal balls, or abscesses, but outside of hospitalized patients, these sequelae are extremely uncommon. Even in high-risk patients, such as immunocompromised individuals, ascending infection is rare. In one study of chronically immunosuppressed transplant patients, only 1 in 100 subjects with candiduria progressed to candidemia. In contrast, candiduria after candidemia from other sources was common.^3,4 At a single medical center, only 0.2% of all urine samples were positive for fungi, almost all of which were Candida. Of that group, only 14 people in more than 100,000 (0.001%) received treatment with antifungals.^4,5

Combine those statistics with molecular genetics studies examining fungal strains in patients with both fungiuria and fungemia. Only one-third of these infections had matching strains of Candida in blood and urine, suggesting that the poor condition of the patient may drive fungal overgrowth systemically. The mortality rate amongst patients with candiduria is high at almost 20%, but less than half of a percent of those deaths could be attributed to candidemia, signifying how fundamentally sick most of these patients are to begin with.

In support of this concept is the substantial documentation of patient risk factors for the progression of fungal urinary infections. Progressive or ascending fungal urinary infections almost always occur in patients who are already sick with some combination of immune system impairment (other illness, diabetes, malignancy) and a urinary tract abnormality, most commonly an obstruction (such as a stone or benign prostatic hyperplasia) or an indwelling urinary device, such as a Foley catheter or nephrostomy tube.

Thus, as urologists, we have a specific role in the management of fungal infection: improving the management of urologic predisposing risk factors. We must relieve obstructions, remove indwelling devices, if possible, exchange them if not possible, and do so using the least invasive approach possible. If there is suspicion of systemic fungal infection, imaging to look for fungal balls, hydronephrosis, or abscesses may be indicated as these could benefit from procedural intervention. This focus on modifying these risk factors comes from the fact that antifungals are often limited in their efficacy. Eradication of urinary fungi in patients treated with antifungals is less than 50%, which is not significantly different than the rates of resolution of fungiuria after removal of indwelling devices.³

As a contributing factor, 85% of patients with fungiuria had some other nonfungal infection treated with antibiotics in the month prior, the most common of which was urinary tract infection in 44%. Fungal populations can expand >1,000-fold after antibiotic treatment, promoting fungiuria, and increasing the risk of later fungemia. This might suggest that ongoing efforts at antibiotic stewardship are even more critical than we might expect; recent increases in pathogenic fungal infections may represent an additional aspect of the global “collateral damage” associated with antibiotic overuse.

In summary, while candiduria is common in some populations, invasive candidemia is rare and primarily restricted to patients who are already very ill. Thus, the decision to proceed with antifungals should be based on the patient’s relative risk and the likelihood they will benefit from therapy. If there is suspicion of a systemic infection, every attempt should be made to resolve underlying risk factors—control the diabetes, remove indwelling devices, relieve urinary tract obstruction—as these interventions alone can be as effective as antifungals.