Candida infections of the bladder and kidneys

INTRODUCTION — Funguria is common in hospitalized patients and is generally benign. Invasive infection of the kidney is unusual and is difficult to treat. The vast majority of fungal infections of the kidney and bladder result from Candida albicans and other Candida species. A variety of other fungi can rarely involve the kidney as a result of disseminated infection. These include:

●Aspergillus species

●Fusarium species

●Trichosporon species

●Mucorales (eg, Rhizopus, Mucor species)

●Dematiaceous molds

●Cryptococcus neoformans

●Dimorphic fungi (eg, Histoplasma capsulatum, Coccidioides species, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Sporothrix schenckii, and Penicillium marneffei)

A review of Candida infections of the bladder and kidney will be presented here. Issues related to fungal peritonitis in patients treated with continuous peritoneal dialysis are presented separately. (See "Fungal peritonitis in peritoneal dialysis".)

PATHOPHYSIOLOGY — There are two mechanisms by which Candida spp infect the urinary tract: infections can begin in the lower urinary tract and ascend to the upper urinary tract, and infection can also occur via hematogenous dissemination to the kidneys.

Mice or rabbits infected intravenously with fungi clear these organisms quickly from their bloodstream. Despite this ability, fungal multiplication is commonly found within the kidney, the only organ in which this appears to occur [1]. Whether fungi preferentially localize in the kidney or are cleared from other organs more efficiently by host defense mechanisms is not understood.

In these animal models, the two key steps in the pathogenesis of fungal renal infection are the attachment of fungi to endothelial surfaces and penetration into tissue. Within five minutes of injection, yeast forms are found in the capillary beds of the kidneys. Since this elicits an inflammatory response, yeasts survive only if they penetrate the capillary walls and invade the interstitium. Invasion is expedited by attachment to the capillary walls via adherence mechanisms. Penetration through the capillary walls is facilitated by the formation of pseudohyphal or hyphal forms [2].

Ascending infection of the kidneys is thought to result from vesicoureteral reflux of fungi from the bladder. However, this mechanism is difficult to demonstrate in animal models. The presence of an indwelling bladder catheter is associated with biofilm formation, and this allows persistent colonization by Candida species [3,4].

EPIDEMIOLOGY AND RISK FACTORS — Candiduria is a common event in hospitalized patients [5,6]. A European observational study found that Candida was the third most common organism isolated from urine in hospitalized patients [7].

A prospective multicenter surveillance study evaluated 861 hospitalized patients with candiduria [8]. Candida albicans was found in 52 percent of these patients and Candida glabrata in 16 percent. The following risk factors were noted: urinary tract drainage devices (83 percent), prior antibiotic therapy (90 percent), diabetes (39 percent), urinary tract pathology (38 percent), and malignancy (22 percent). Only 11 percent had no underlying predisposing factors for funguria. Urinary tract infections associated with drainage devices, diabetes, or urinary tract abnormalities are considered complicated. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults and adolescents".)

Candiduria is especially common among patients in intensive care units (ICUs); older age, diabetes mellitus, length of stay, ventilator support, and parenteral nutrition were found to be risk factors in one study [9]. Other studies have noted similar risk factors in ICU patients [10].

Community-based studies have been reported infrequently, but they generally note similar risk factors (eg, diabetes, antimicrobial use, indwelling bladder catheters) as those in hospitalized patients [11].

INFECTION VERSUS COLONIZATION — Most patients with candiduria are asymptomatic, and the yeasts merely represent colonization [12]. However, it is difficult to differentiate between colonization and bladder infection.

●Infected patients may have dysuria, frequency, and suprapubic discomfort, but others have no symptoms [8].

●Pyuria is so common in patients with a chronic indwelling bladder catheter that it cannot be used to indicate infection. (See "Catheter-associated urinary tract infection in adults".)

●Neither the presence of pseudohyphae in the urine nor the number of colonies growing in culture (unlike bacterial urine cultures) help to distinguish colonization from infection.

The diagnostic modalities used to distinguish infection from colonization are discussed below. (See 'Diagnosis' below.)

NATURAL HISTORY — There are several concerns in patients with asymptomatic candiduria: the development of ascending infection of the kidney, the development of candidemia, and the possibility that candiduria is a manifestation of disseminated candidiasis. These complications should be considered in the appropriate host:

●Ascending involvement of the kidneys usually occurs in the setting of urinary tract obstruction, which may be caused by formation of fungus balls [13]. Complications of upper tract infection, such as emphysematous pyelonephritis and papillary necrosis, are rare [14-16].

●Candiduria as a source of candidemia typically occurs in patients who have urinary tract abnormalities, most often urinary tract obstruction, and/or in those who have undergone a urinary tract procedure [17-19]. Candidemia as a consequence of asymptomatic candiduria without obstruction or surgery is uncommon in hospitalized patients, including those in the intensive care unit setting [8,10]. A study assessing the molecular relatedness of strains of Candida found that only 12 of 141 episodes of candidemia had concomitant candiduria. Of these 12, 6 had different species in urine and blood, and 2 had genetically unrelated strains of the same species in urine and blood. Only 4 patients, representing 2.8 percent of all candidemias at this medical center, had related strains of Candida in urine and blood [20].

●The kidneys are the most commonly involved organ in disseminated candidiasis. Although candiduria can be seen in systemic infection, it is usually accompanied by many other signs and symptoms of disseminated infection.

Renal transplantation was previously thought to be a risk factor for ascending infection and candidemia when candiduria was present. A nested case-control study of 192 renal transplant recipients who developed candiduria was performed to assess the epidemiology of candiduria in a large population of 1738 transplant recipients over an eight-year period [21]. The study demonstrated the following results:

●Risk factors for developing candiduria were similar to those described for non-transplant patients in prior studies [8].

●Candidemia occurred in only 5 percent of patients with candiduria.

●Treatment with an antifungal agent did not result in a greater likelihood of clearing Candida from the urine when compared with simple catheter removal.

●Although patients with candiduria had worse survival compared to those without candiduria, treatment of candiduria was not associated with a survival benefit.

A limitation of this study is that it did not address some of the specific questions that arise in kidney transplant recipients who have asymptomatic candiduria early after transplantation when ureteral stents are in place. During this time period, ureteral obstruction from fungus balls and allograft pyelonephritis has been described. Further study is necessary to address the utility of antifungal therapy in this setting.

CLINICAL CHARACTERISTICS — The clinical characteristics of kidney infections depend on whether the disease presents secondary to candidemia or from an ascending bladder infection.

Candidemia-associated infection — Infection of the kidney associated with candidemia is usually bilateral, consisting of multiple microabscesses in the cortex and medulla (picture 1).

The kidney is the most common organ involved in systemic Candida infections. This was illustrated in a review of 45 autopsies of patients with disseminated candidiasis: 40 had histological evidence of renal involvement compared with 26 with evidence of invasion of the heart, the next most commonly involved organ [22].

When present, symptoms and signs referable to renal infection include the following:

●Flank and/or abdominal pain

●Costovertebral angle tenderness

●Abdominal tenderness

Kidney infection in premature neonates may be associated with severe manifestations; polymorphonuclear leukocytes in these hosts may not ingest and kill the yeast normally [23]. (See "Clinical manifestations and diagnosis of Candida infection in neonates", section on 'Urinary tract infection'.)

Renal function is only rarely compromised in adults. In neonates, however, there seems to be a higher propensity for fungus ball formation with resulting obstruction and serious renal impairment [23-25].

Papillary necrosis can occur, and the sloughed papillae may serve as a nidus for fungus ball formation. Although it is uncommon for Candida to invade vascular structures and cause infarction, there are reports of renal infarction secondary to emboli in patients with Candida endocarditis.

Ascending infection — Ascending Candida infection of the kidney usually has a subacute to chronic course. Invasion of the renal parenchyma in such patients tends to involve the renal pelvis and medulla with sparing of the cortex. The kidney is usually the only organ involved and the infection tends to be unilateral. Fungus balls and perinephric abscesses can occur, as can emphysematous pyelonephritis; the latter complication occurs rarely. Emphysematous pyelonephritis is characterized on imaging by air in the collecting system or renal parenchyma [14,15]. (See "Emphysematous urinary tract infections".)

Ascending infections occur mostly in patients with diabetes or anatomic abnormalities of the urinary tract. Among diabetic patients, abnormalities, such as an atonic bladder and glucosuria, promote the chronic presence of fungi in the urinary tract.

Predisposing urinary tract abnormalities include:

●Renal stones causing obstruction

●Renal stone manipulation with percutaneous lithotripsy or ureteroscopy

●Nephrostomy tubes

●Prostatic hypertrophy

●Neurogenic bladder

●Infected penile prosthesis

●Chronic bladder catheterization

Flank pain may be present for days to weeks and costovertebral angle tenderness can be elicited in some patients. Fever or other signs of systemic infection are usually absent.

DIAGNOSIS — When only isolated candiduria is found, it can be difficult to distinguish among contamination of the urine sample, colonization of the bladder, local bladder infection, and upper tract disease involving the renal parenchyma [6,26].

Urine characteristics, such as the number of yeast or the presence of pyuria, do not distinguish fungal colonization from fungal infection. Although uncommonly found, the identification of fungal casts in urine cytology specimens stained with periodic acid-Schiff or silver stains is diagnostic of kidney involvement [27].

Persistent candiduria, especially in diabetics, should prompt radiologic imaging of the kidneys with ultrasound or computed tomography (CT) to evaluate for renal involvement. Abdominal CT scans or sonography may show hydronephrosis, fungus balls, or perinephric abscesses associated with ascending infection [28,29].

Patients with candiduria who have systemic signs or symptoms should be evaluated for disseminated infection with imaging and blood cultures. Among patients with known disseminated candidiasis, the finding of renal involvement has no specific treatment implications unless renal function deteriorates or flank pain develops.

The diagnosis of patients with candidemia and invasive candidiasis is discussed separately. (See "Clinical manifestations and diagnosis of candidemia and invasive candidiasis in adults", section on 'Diagnosis'.)

TREATMENT — Updated Infectious Diseases Society of America (IDSA) guidelines for the treatment of candidiasis were published in 2016 [30], and a literature review summarizing the treatment of Candida urinary tract infections was published in 2011 [31]. These recommendations, along with our treatment suggestions, are summarized in the following discussion.

Asymptomatic candiduria — Asymptomatic candiduria rarely requires antifungal therapy unless it occurs in the setting of a condition that confers high risk of dissemination (neutropenia, very low birthweight infants (<1500 g), or urinary tract manipulation) [30].

Antifungal therapy is not recommended unless the patient belongs to one of the groups listed above.

In contrast, patients who have a risk factor for disseminated infection should be treated as follows:

●Neutropenic patients and very low birthweight infants (<1500 g) with asymptomatic candiduria should be assumed to have disseminated infection and should be treated with an antifungal regimen recommended for candidemia. (See "Management of candidemia and invasive candidiasis in adults".)

●Patients with asymptomatic candiduria who will be undergoing a urologic procedure can be treated with oral fluconazole 400 mg (6 mg/kg) or amphotericin B deoxycholate 0.3 to 0.6 mg/kg intravenously (IV) daily for several days before and after the procedure.

Renal transplantation is no longer an absolute indication for treatment of asymptomatic candiduria, but therapy should be considered on a case-by-case basis [21]. Candiduria is most often treated in renal transplant recipients when there is a high risk for graft or device involvement, such as early after transplant when ureteral stents are in place.

Imaging of the urinary system should be considered in patients who have persistent candiduria and who may be at increased risk for formation of fungus balls. This includes diabetics, those who have other urologic abnormalities that may predispose to fungus ball formation, and neonates [30].

Among asymptomatic patients without these risk factors, antifungal therapy has not been proven to be of value because rapid recurrence is common, selection of resistant Candida species is possible, and clinical outcomes do not appear to be improved [8,32-34]. The following observations illustrate the range of findings:

●A randomized, double-blind trial compared fluconazole to placebo in 316 patients with candiduria and minimal or no symptoms [32]. Fluconazole therapy resulted in a significantly higher rate of eradication of the organism (50 versus 29 percent overall), especially for those who received 14 days of therapy and did not have a urinary catheter in place (78 versus 47 percent). However, cultures obtained 14 days after completion of treatment showed no difference between the groups; candiduria was present in 32 percent of those who had received fluconazole and 35 percent of placebo recipients.

●A rapid recurrence of funguria after antifungal therapy is discontinued (82 percent at 30 days) was also noted in another randomized trial in which oral fluconazole was compared to bladder irrigation with amphotericin B [33].

●A prospective, multicenter observational study cited above evaluated 861 hospitalized patients with funguria, almost all due to Candida species and almost all with asymptomatic funguria [8]. Clinical outcome data were available for 530 patients. Resolution of funguria occurred in 76 percent of patients who received no specific antifungal therapy, 35 percent of patients who were treated with urinary catheter removal alone, and 50 percent of patients treated with fluconazole or amphotericin B bladder wash.

The overall mortality was 20 percent, but only seven patients (1.3 percent) developed candidemia. Thus, mortality reflected the underlying disease rather than fungal infection. This conclusion is consistent with the findings in a retrospective review of 149 hospitalized patients with asymptomatic funguria in which neither risk reduction nor antifungal therapy affected morbidity and mortality [34].

Given the lack of efficacy of antifungal therapy for asymptomatic candiduria, attention should be focused upon reducing risk factors for acquisition of candiduria, such as removal of bladder catheters or urologic stents and discontinuation of antibiotics [8,34]. If complete removal of bladder catheters or urologic stents is not possible, placement of new devices or intermittent bladder catheterization may decrease colonization.

A review of 243 patients with asymptomatic candiduria at four United States medical centers found that 43 percent were treated inappropriately with antifungal agents that were not indicated, a third were given an antifungal agent, almost always fluconazole, for more than 7 days, and 5 percent received more than 14 days of an antifungal agent [35].

Symptomatic candiduria — Symptomatic candiduria should be treated [6,30]. Only a few agents are available for antifungal therapy for localized bladder or kidney infections (table 1). While awaiting species identification and susceptibility results, we give an antifungal agent that will target the most likely species (which will depend on the patient's medical history and past microbiology data) and that will achieve adequate concentrations in the urine. For patients who are not at risk for fluconazole-resistant Candida infection, we give fluconazole. For patients at risk for fluconazole-resistant Candida infection, we give amphotericin B deoxycholate. Dosing is discussed below. (See 'Fluconazole-susceptible Candida' below and 'Fluconazole-resistant Candida' below and "Candidemia in adults: Epidemiology, microbiology, and pathogenesis".)

Treatment of candiduria should be tailored according to the identified Candida species and according to whether localized or disseminated infection is present. For patients with candiduria with suspected disseminated candidiasis, treatment should be chosen according to the recommendations for systemic infection. (See "Management of candidemia and invasive candidiasis in adults".)

The treatment of fungus balls is discussed below. (See 'Fungus balls' below.)

Fluconazole-susceptible Candida — For cystitis due to fluconazole-susceptible Candida spp, we recommend fluconazole (200 mg [3 mg/kg] orally daily). For pyelonephritis due to fluconazole-susceptible Candida, we recommend fluconazole (200 to 400 mg [3 to 6 mg/kg] orally daily) (table 1). Therapy should be continued for 14 days for both cystitis and pyelonephritis.

Fluconazole is excreted into the urine in its active form and achieves urine levels exceeding the minimum inhibitory concentration for most Candida isolates [30]. Dosing of fluconazole should be reduced in patients with renal insufficiency. Most patients will respond to these regimens; however, recurrence of funguria is common after antifungal therapy is discontinued [32,33].

Fluconazole-resistant Candida — Patients with cystitis or pyelonephritis caused by fluconazole-resistant Candida spp can be treated with intravenous amphotericin B deoxycholate (0.3 to 0.6 mg/kg per day) for one to seven days (table 1). For patients with pyelonephritis, flucytosine may be added to amphotericin B deoxycholate. Lipid formulations of amphotericin B should not be used to treat urinary tract infections because they do not penetrate the kidney or achieve adequate concentrations in the urine [30].

Bladder irrigation with amphotericin B will clear funguria, but the effect is transient, and this treatment is not recommended for cystitis; it will clearly not be effective for pyelonephritis [30,33,36].

In patients with urinary tract infection caused by fluconazole-resistant Candida spp, such as C. glabrata, monotherapy with flucytosine (25 mg/kg four times per day, with appropriate dose reduction in patients with renal insufficiency) can be used as an alternative to IV amphotericin B deoxycholate (table 1) [30]. Flucytosine should be continued for 7 to 10 days for cystitis and for 14 days for pyelonephritis. However, the development of resistance to flucytosine is common, particularly when used as the sole antifungal agent. Flucytosine monotherapy can be tried prior to giving IV amphotericin B deoxycholate for patients who are not hospitalized and for those who have renal insufficiency. Flucytosine should not be used for patients who have C. krusei infection because this species is resistant to flucytosine.

Careful laboratory monitoring of patients receiving flucytosine is necessary, given its potential for hematologic and hepatic toxicity, particularly in the setting of renal insufficiency. (See "Pharmacology of flucytosine (5-FC)".)

The efficacy of echinocandins has been addressed in series with small numbers of patients and in individual case reports [37-44]. Most of these studies were retrospective assessments of eradication of Candida from the urine of patients who received either caspofungin or micafungin. Caspofungin was noted to successfully eradicate candiduria in six patients with candiduria who participated in phase II-III clinical studies of this agent [37], but others have reported failure of caspofungin for treating Candida glabrata urinary tract infection [38,39]. One report of five patients noted clearance of C. glabrata in four patients and C. albicans in one patient treated with micafungin [40]. Another study noted symptom resolution in 8 of 12 patients with symptomatic candiduria treated with micafungin and sterilization of urine in the 6 patients who had follow-up cultures performed [43]. In a multicenter retrospective study that evaluated 128 cases of candidemia with a presumed urinary tract source, echinocandin use did not appear to alter the risk of clinical failure; clinical failure occurred in 7 (20 percent) patients treated with an echinocandin and 15 (17 percent) of patients treated with fluconazole [44].

Because of the retrospective nature of these reports, follow-up cultures after initial eradication were often not performed and factors, such as catheter removal, could not be controlled. One study noted that although urine levels of micafungin were low (0.04 to 0.61 ug/mL), they appeared to be adequate to eradicate Candida from the urine in four of six patients [42]. Thus, the evidence that echinocandins, especially micafungin, might be effective in treating Candida urinary tract infections is not firm, but the data are intriguing and could offer the possibility of salvage therapy for patients who have urinary tract infections with fluconazole-resistant Candida species, such as C. glabrata.

Experience with other agents — There is little clinical experience in treating Candida infections of the kidney or bladder with voriconazole, posaconazole, or isavuconazole, none of which achieve adequate concentrations in the urine for treating infection. However, these drugs perhaps could achieve appropriate levels in patients with invasive infections involving the renal or bladder parenchyma. Their use should only be considered in the absence of alternative therapies.

COMPLICATIONS — Complications associated with fungal infections of the kidneys include perinephric abscess and fungus ball formation. Additional complications, such as renal arteritis with aneurysm formation, have been observed in renal transplant recipients who have acquired Candida infections at the time of transplantation [45].

Perinephric abscess — With fungal perinephric abscesses, drainage is preferred and can often be performed with percutaneous catheters. Large bore catheters and irrigation may be required since the abscess material can be especially thick and tenacious. Patients with multiple loculations or fistulae may require open drainage for complete evacuation.

Although some patients have been cured with drainage alone, it is recommended that systemic antifungal drugs should be given to all patients with perinephric abscesses [16].

Fungus balls — Fungus balls (sometimes called fungal bezoars) should be managed with a combination of surgical and medical therapy [30].

We recommend fluconazole (200 to 400 mg [3 to 6 mg/kg] orally once daily). We suggest amphotericin B deoxycholate (0.3 to 0.6 mg/kg intravenously daily) with or without flucytosine (100 mg orally per day divided into four doses) as an alternative regimen. Therapy should be continued until a surgical or endoscopic procedure to remove the fungus ball has been accomplished, symptoms have resolved, and urine cultures are negative.

The following represents a sequential approach to the surgical management of fungus balls [13]:

●Systemic therapy with an antifungal agent is imperative during any manipulation of the urinary tract to prevent hematogenous dissemination.

●The first step is obtaining access to the involved upper tract with either percutaneous nephrostomy tubes or retrograde catheters passed through the ureter.

●If a nephrostomy tube is present, irrigation of the involved upper tract with amphotericin B deoxycholate (25 to 50 mg in 200 to 500 mL sterile water) should be performed [30].

●Debulking by extraction of the fungus ball through the catheters and lavage should be attempted.

●After debulking, some authorities suggest irrigation via the catheters until urine cultures are negative and there is no radiologic evidence of persistent disease.

●Balloon dilatation of inflammatory strictures may be required to reestablish drainage through the ureters; some infections will need open pyelotomy for debridement.

Prostate abscess — Prostate abscess due to Candida species is an unusual complication of candiduria [46-48]. Cases typically occur in older men with diabetes mellitus. Presenting symptoms are variable; usually patients have pelvic discomfort and urinary retention. Urine cultures usually grow Candida, and imaging with transrectal ultrasound or computed tomography may demonstrate the collection within the prostate. We favor drainage of such collections by an interventional radiologist; this is helpful for mycologic diagnosis as well as treatment.

In addition, treatment should consist of antifungal therapy; fluconazole is preferred given the greatest clinical experience with this agent. In the setting of azole-resistant organisms, echinocandins or amphotericin B may be used [49]. The concentration of various antifungal agents achieved in the prostate has not been well studied, but likely are above the minimum inhibitory concentration of the organism in the face of active inflammation and tissue necrosis seen with prostatic abscess.

The duration of therapy should be individualized based on clinical response to drainage and underlying comorbidities; we favor antifungal therapy for at least four weeks following adequate drainage. For highly loculated collections that cannot be drained adequately, we would extend the duration of antifungal therapy. For patients with infection limited to the prostate gland who fail to respond to drainage and antifungal therapy, transurethral resection of the prostate may be considered.

Renal transplant infection — A retrospective study suggested that organ contamination at the time of renal transplantation can lead to Candida infection of the allograft, although this occurred rarely [45]. Among 18 renal transplant recipients who developed graft site candidiasis, 14 had renal arteritis (13 with aneurysm formation). Less frequent findings were urinoma, graft site abscesses, and surgical site infections. Other reports have described pseudoaneurysm formation [50].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Candidiasis".)

SUMMARY AND RECOMMENDATIONS

●Epidemiology and risk factors – Candiduria is common in hospitalized patients and is generally benign, whereas invasive infection of the kidney is unusual. Risk factors for candiduria include urinary tract drainage devices, prior antibiotic therapy, diabetes, urinary tract pathology, and malignancy. (See 'Epidemiology and risk factors' above.)

●Clinical manifestations – Most patients with candiduria are asymptomatic, and the yeast merely represents colonization. In patients with true infection, symptoms and signs may include dysuria, frequency, suprapubic discomfort, flank and/or abdominal pain, costovertebral angle tenderness, and abdominal tenderness. (See 'Clinical characteristics' above.)

●Diagnostic evaluation – In patients with isolated candiduria and no localizing symptoms, it can be difficult to distinguish among colonization, local bladder infection, and upper tract disease involving the renal parenchyma. Urine characteristics, such as the number of yeast or the presence of pyuria, do not distinguish fungal colonization from fungal infection. (See 'Infection versus colonization' above and 'Diagnosis' above.)

Persistent candiduria, especially in diabetics, should prompt radiologic imaging of the kidneys with ultrasound or computed tomography (CT) to evaluate for renal involvement. Abdominal CT scans or sonography may show hydronephrosis, fungus balls, or perinephric abscesses associated with ascending infection. (See 'Diagnosis' above.)

Patients with candiduria who have systemic signs or symptoms should be evaluated for disseminated infection with imaging and blood cultures. (See 'Diagnosis' above.)

●Management of asymptomatic candiduria – Asymptomatic candiduria rarely requires antifungal therapy, unless it occurs in the setting of neutropenia, in very low birthweight infants (<1500 g), or in patients who will undergo urinary tract manipulation. Imaging of the urinary system should be considered in patients who have persistent candiduria and who may be at increased risk of formation of fungus balls, such as diabetics, those who have other urologic abnormalities that may predispose to fungus ball or abscess formation, and neonates. (See 'Asymptomatic candiduria' above.)

●Management of symptomatic candiduria – Symptomatic candiduria should be treated. Empiric antifungal therapy should target the most likely species as determined by the patient's medical history and past microbiology data (table 1). Once a species is identified, treatment should be tailored. If disseminated candidiasis is suspected, treatment should be chosen according to the recommendations for systemic infection. (See 'Symptomatic candiduria' above and "Management of candidemia and invasive candidiasis in adults".)

•Fluconazole-susceptible Candida – For cystitis due to fluconazole-susceptible Candida spp, we recommend fluconazole (200 mg [3 mg/kg] orally daily) (table 1) (Grade 1B). For pyelonephritis due to fluconazole-susceptible Candida, we recommend fluconazole (200 to 400 mg [3 to 6 mg/kg] orally daily) (Grade 1B). Therapy should be continued for 14 days for both cystitis and pyelonephritis. (See 'Fluconazole-susceptible Candida' above.)

•Fluconazole-resistant Candida – For cystitis or pyelonephritis caused by fluconazole-resistant Candida spp, we recommend intravenous amphotericin B deoxycholate (0.3 to 0.6 mg/kg per day) (table 1) (Grade 1C). Therapy should be continued for one to seven days. For pyelonephritis, flucytosine (25 mg/kg four times per day, with appropriate dose reduction in patients with renal insufficiency) may be added to amphotericin B deoxycholate. Flucytosine monotherapy (25 mg/kg four times per day) can be tried for patients who are not hospitalized and for those who have renal insufficiency. For recalcitrant cases of fluconazole-resistant Candida infection, or if amphotericin B deoxycholate or flucytosine cannot be used, we suggest salvage therapy with micafungin (Grade 2C).

Lipid formulations of amphotericin B should not be used to treat urinary tract infections because they do not penetrate the kidney or achieve adequate concentrations in the urine. There is little clinical experience in treating Candida infections of the kidney or bladder with voriconazole, posaconazole, or isavuconazole, none of which achieve adequate concentrations in the urine for treating infection. (See 'Fluconazole-resistant Candida' above and 'Experience with other agents' above.)

●Management of complications (eg, fungus balls, perinephric abscess, prostate abscess) – Fungus balls, perinephric abscess, and prostate abscesses are typically managed with a combination of surgical intervention (or drainage) and antifungal therapy. Renal transplant infections are associated with complications that often require surgical or other intervention. (See 'Fungus balls' above and 'Perinephric abscess' above and 'Prostate abscess' above and 'Renal transplant infection' above.)