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Fungal urinary tract infections in patients at risk
International Journal of Antimicrobial Agents 11 (1999) 289 – 291
Original article
Fungal urinary tract infections in patients at risk S. Krcmery a,*, M. Dubrava a, V. Krcmery Jr. b a
Department of Geriatric Medicine, Comenius Uni6ersity School of Medicine, Dumbierska 3, 831 01 Bratisla6a, Slo6ak Republic b Department of Clinical Pharmacology, St. Elisabeth Cancer Institute, Bratisla6a, Slo6ak Republic
Abstract Fungal urinary tract infection (UTI) represents a high-risk event in severely ill patients. Its increasing incidence in recent years is associated with extensive and prolonged use of broad-spectrum antimicrobial agents, corticosteroids, immunosuppressive and cytotoxic drugs. Other important risk factors comprise higher age, diabetes mellitus, chronic renal failure, hemodialysis, renal transplantation, structural or functional abnormalities of urinary tract with indwelling urinary catheter or nephrostomy. Fifty hospitalized symptomatic patients with funguria of \ 105 CFU/ml and leucocyturia were analysed for etiology, risk factors and outcome. Candida albicans was isolated in 36 patients, non-albicans Candida species (Candida tropicalis, Candida krusei ) and non-Candida yeasts (Blastoschizomyces capitatus) in 14 patients, respectively. All patients were treated with systemic antifungals. In total, 42 patients of 50 (84%) were cured (32/36 with C. albicans and 10/14 with non-C. albicans associated funguria). Systemic antifungal therapy should be considered in high-risk patients with fungal UTI. © 1999 Elsevier Science B.V. All rights reserved. Keywords: Fungal urinary tract infection; Systemic antifungals; High-risk patients
1. Introduction The incidence of candiduria and fungal urinary tract infections (UTI) has increased in recent years. Risk factors comprise the extensive use of broad-spectrum antimicrobial agents, corticosteroids, immunosuppressive agents, cytotoxic chemotherapy complicated by mucositis and neutropenia, elderly age, diabetes mellitus, structural or functional abnormalities of urinary tract with indwelling urinary catheter or nephrostomy. Increased incidence is also observed in chronic renal failure and hemodialysis patients. Renal transplant patients are at high risk for developing funguria and pyelonephritis due to immunosuppressive therapy [1– 3]. The most frequent organism causing fungal UTI is still Candida albicans followed by Candida (Torulopsis) glabrata, Candida tropicalis, and Candida krusei [1,4]. * Corresponding author. Tel.: + 421-7-373628; fax: + 421-7325754.
Non-albicans Candida and non-Candida yeasts are steadily increasing as the ethiological cause of fungal UTI [4]. In comparison with bacterial UTI, the diagnostic criteria of significant funguria and fungal UTI are not well established. Wise et al. [5] concluded that an increased risk of fungal pyelonephritis was associated with counts of greater than 15 000 CFU/ml. Other authors [6,7] defined the cut-off between colonization and infection as the lowest colony count from a single urine specimen to be 105 CFU/ml of fungal pathogen. In 5–15% of patients with symptomatic fungal UTI, funguria is accompanied by fungemia [4].
2. Patients and methods A total of 50 patients hospitalized in the years 1990– 1995 with fungal UTI were analysed. There were 26 males and 24 females with a mean age of 62.4 years. Inclusion criteria were cultural documentation of funguria (\ 105 CFU/ml), leucocyturia (\10/HPF ×400),
0924-8579/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved. PII: S 0 9 2 4 - 8 5 7 9 ( 9 9 ) 0 0 0 3 2 - 1
290
S. Krcmery et al. / International Journal of Antimicrobial Agents 11 (1999) 289–291
fever \38°C and typical symptoms of UTI (dysuria, frequent urination, lumbar pain or tenderness, etc.). Yeasts from urine were identified with API or Mycotube (Roche), and with Vitek Systems since 1993. Systemic antifungals (fluconazole, ketoconazole, itraconazole or amphotericin B) were used in all patients with regard to the type of isolated yeasts and their sensitivity patterns. All patients were analysed for risk factors, age and sex, renal function, presence of UTI complicating factors, spectrum of isolated yeasts, therapy and outcome. All patients were evaluated 3 – 10 days after the end of therapy (early follow-up) and 21 – 28 days after the end of therapy (late follow-up). Therapeutic success (cure) was defined as the resolution of clinical symptoms and sterile urine (funguria B103 CFU/ml). Persistent funguria ( ]103 CFU/ml) was recorded as therapeutic failure, even if no other signs or symptoms of infection were present. The x 2 test was used to check the comparability of patients characteristics. P values B 0.05 were considered significant.
3. Results The most frequent risk factors for development of symptomatic fungal UTI were: antibiotic therapy with more than one agent in the previous 7 days (96%), previous therapy with corticosteroids (72%), concomitant fungal infection or colonisation in a localisation other than the urinary tract (48%), indwelling urinary catheter or nephrostomy (46%), hematological malignancies with neutropenia (30%), structural or anatomical abnormalities of the urinary tract (26%), and diabetes mellitus (12%). Nine patients (18%) had significantly impaired renal function (mean serum creatinine 208 mmol/l). Only two of 50 patients did not receive any antimicrobials in the previous 7 days. Eighteen patients were previously treated with one antibiotic, 18 with two, and 12 with three or more antibiotics. Most frequently administered antimicrobial agents were third-generation cephalosporins (40 of 50 patients), and fluoroquinolones (33 of 50 patients). The distribution of yeasts isolated from urine prior to therapy is shown in Table 1. C. albicans was isolated from Table 1 Fungal urinary tract infections—isolated organisms Organism
Number of patients
Candida albicans Candida tropicalis Blastoschizomyces capitatus Candida krusei
36 5 5 4
Total
50
Table 2 Fungal urinary tract infections — antifungal chemotherapy Therapy
Cured
Failed
Total
n
%
n
%
n
%
Fluconazole Ketoconazole Itraconazole Amphotericin B
25 12 3 2
86.2 85.7 100.0 50.0
4 2 0 2
13.8 14.3 0.0 50.0
29 14 3 4
100 100 100 100
Total
42
84.0
8
16.0
50
100
36 patients, C. tropicalis and B. capitatus from five, and C. krusei from four patients, respectively. Only two patients had fungaemia. Simultaneous significant bacteriuria (] 105 CFU/ml) was present from 20 of 50 patients with fungal UTI (40%). Enterobacteriaceae were isolated in 12 patients, Pseudomonas aeruginosa from five and Enterococcus faecalis from three patients. Fluconazole was used in 29 patients (25 cured), ketonazole in 14 patients (12 cured), itraconazole in three patients (all cured) and systemic amphotericin B from four patients (two cured) (Table 2). In total, 42 of 50 patients (84%) were cured (32/36 with C. albicans and 10/14 with non-C. albicans associated funguria). Eight patients with fungal UTI died despite systemic antifungal therapy. There was no statistically significant difference between subgroups with regard to sex, renal function, etiology and treatment. There was no difference in number of deaths between C. albicans and non-C. albicans associated fungurias. All deaths except one were associated with terminal underlying disease and/or multiorgan failure. 4. Discussion It is widely accepted that patients with symptomatic fungal UTI require therapy. Cases of fungal pyelonephritis [8], papillary necrosis [9] and fungal bezoar formation [10] have been reported in the literature. Asymptomatic funguria in high-risk patients (e.g. renal transplant, obstructive uropathy, neutropenia, diabetes mellitus, immunocompromised patients) should also be treated [1,3,11]. If a urinary catheter or nephrostomy cannot be removed, the use of antifungal bladder irrigation should be considered. At present, amphotericin B is the most widely used agent for this type of treatment [12,13]. It appears that the irrigation is well tolerated without any serious adverse effects. Sanford [14] suggests that low amphotericin B concentrations (5–10 mg/l) may be efficacious and less toxic to the bladder mucosa. He recommends the administration of amphotericin B by triple-lumen catheter with cross-clamping for 60–90 min. Two days of irrigation with the above-mentioned concentration of the drug should be sufficient and adequate [1,14].
S. Krcmery et al. / International Journal of Antimicrobial Agents 11 (1999) 289–291
For systemic antifungal therapy, flucytosin nowadays plays a limited role in the treatment of fungal UTI due to its toxicity and marginal efficacy. The dose reduction in patients with compromised renal function is inevitable [2]. Ketoconazole is primarily eliminated via hepatic metabolism and only a small percentage of the drug is excreted in urine [1,3]. For the treatment of candiduria, recommended daily oral doses are 200 – 400 mg. Nevertheless, the eradication rates reported for the treatment of candiduria are approximately 60 – 65% [15,16]. Ketoconazole is associated with occasional gastrointestinal side-effects, hepatotoxicity and gynecomastia. It downregulates the P450 cytochrome enzyme system and interacts with drugs (including cyclosporine) metabolised through this system [3]. Fluconazole, a triazole antifungal agent, has a high oral bioavailability (\ 90%), long half-life (\ 30 h) and is primarily excreted unchanged in urine (80%), resulting in adequate urinary drug concentrations to treat candiduria [1,2]. It is effective against C. albicans and against the most common non-albicans Candida species, although higher doses may be required for infections caused by C. glabrata [17]. Infections caused by C. krusei should not be treated with fluconazole. Recommended daily doses are 200 – 400 mg (orally or i.v.) with the dosing interval of 24 h. Fluconazole is generally well tolerated and dose reduction should be considered in patients with chronic renal failure [1,17]. Systemic administration of amphotericin B should be reserved for severe systemic fungal infections caused by resistant yeasts. Only about 3% of an i.v. dose of the drug is excreted unchanged in the urine; however, it is associated with an extensive tissue distribution [1]. Liposomal amphotericin is an effective alternative in patients who are at risk for nephrotoxic side-effects, although it is unlikely that patients with renal insufficiency would achieve sufficient urinary levels of amphotericin B to treat funguria effectively [1,3]. Itraconazole, a new antifungal agent, is renally excreted only in about 35% and has practically no advantages over fluconazole in the treatment of fungal UTI [2]. The usual daily oral dose is 200 – 400 mg. Itraconazole is not dialysable and there is no need to change the dosing in renal failure.
5. Conclusions Fungal UTIs in severely ill patients represent a highrisk event. Yeast isolation and sensitivity testing in these patients is helpful in finding the optimal antifungal chemotherapy. Our results confirmed good efficacy of systemic antifungal chemotherapy in high-risk patients with fungal UTI. Patients with documented candiduria
291
should have their urinary catheters removed, if possible. Treatment of asymptomatic and low-risk patients is not required. These patients should be re-cultured and observed after the urinary catheter has been removed. The preferred therapy for symptomatic and high-risk patients without catheter or after its removal, is fluconazole. If the urinary catheter cannot be removed, amphotericin B bladder irrigation for 2–3 days should be considered. In patients with persistent funguria after treatment, complicating factors (obstructive uropathy, stones, etc.) have to be ruled out. Future studies should evaluate the efficacy of new antifungal agents and long-term antifungal prophylaxis in high-risk patients.
References [1] Guglielmo BJ, Stoller ML, Jacobs RA. Management of candiuria. Int J Antimicrob Agents 1994;4:135 – 9. [2] Kraatz G. Therapie der Pilzinfektion. Nieren- Hochdruckkr 1996;25:572 – 4. [3] Krcmery S. Urinary tract infections in renal transplant patients. In: Bergan T, editor. Urinary tract infections. Basel: Karger, 1997:48 – 52. [4] Oravcova E, Lacka J, Drgona L, et al. Funguria in cancer patients: analysis of risk factors, clinical presentation and outcome. Infection 1996;24:319 – 23. [5] Wise GJ, Goldberg P, Kozinn PJ. Genitourinary candidosis: diagnosis and treatment. J Urol 1976;116:778 – 80. [6] Gubbins PO, Piscitelli SC, Danzinger LH. Candidal UTI: A comprehensive review of their diagnosis and management. Pharmacotherapy 1993;13:110 – 6. [7] Ang BSP, Telenti A, King B, Sheckelberg MJ, Wilson WR. Candidemia from a urinary tract source. Clin Inf Dis 1993;17:662– 5. [8] Kauffman CA, Tan JS. Torulopsis glabrata renal infection. Am J Med 1974;57:217 – 24. [9] Knepshield JH, Feller HA, Leb DE. Papillary necrosis due to Candida albicans in renal allograft. Arch Intern Med 1968;122:441 – 4. [10] Irby PB, Stoller ML, McAninch JW. Fungal bezoars of the upper urinary tract. J Urol 1990;143:447 – 51. [11] Rubin RH. Infectious disease complications of renal transplantation. Kidney Int 1993;44:221 – 36. [12] Wise GJ, Kozinn PJ, Goldberg P. Amphotericin B as a urologic irrigant in the management of noninvasive candiduria. J Urol 1982;128:82 – 4. [13] Hsu CCS, Ukleja B. Clearance of Candida colonizing the urinary bladder by a two-day amphotericin B irrigation. Infection 1990;18:280 – 2. [14] 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 – 50. [15] Heel RC. Systemic candidosis and candiduria. In: Levine HB, editor. Ketoconazole in the management of fungal disease. New York: ADIS Press, 1981:115 – 8. [16] Graybill JR, Galgiani JN, Jorgensen JH, Strandberg DA. Ketoconazole therapy for fungal urinary tract infections. J Urol 1983;129:68 – 70. [17] Van’t Wout JW. Fluconazole treatment of candidal infections caused by non-albicans Candida species. Eur J Clin Microbiol Infect Dis 1996;15:238 – 42.
Original article
Fungal urinary tract infections in patients at risk S. Krcmery a,*, M. Dubrava a, V. Krcmery Jr. b a
Department of Geriatric Medicine, Comenius Uni6ersity School of Medicine, Dumbierska 3, 831 01 Bratisla6a, Slo6ak Republic b Department of Clinical Pharmacology, St. Elisabeth Cancer Institute, Bratisla6a, Slo6ak Republic
Abstract Fungal urinary tract infection (UTI) represents a high-risk event in severely ill patients. Its increasing incidence in recent years is associated with extensive and prolonged use of broad-spectrum antimicrobial agents, corticosteroids, immunosuppressive and cytotoxic drugs. Other important risk factors comprise higher age, diabetes mellitus, chronic renal failure, hemodialysis, renal transplantation, structural or functional abnormalities of urinary tract with indwelling urinary catheter or nephrostomy. Fifty hospitalized symptomatic patients with funguria of \ 105 CFU/ml and leucocyturia were analysed for etiology, risk factors and outcome. Candida albicans was isolated in 36 patients, non-albicans Candida species (Candida tropicalis, Candida krusei ) and non-Candida yeasts (Blastoschizomyces capitatus) in 14 patients, respectively. All patients were treated with systemic antifungals. In total, 42 patients of 50 (84%) were cured (32/36 with C. albicans and 10/14 with non-C. albicans associated funguria). Systemic antifungal therapy should be considered in high-risk patients with fungal UTI. © 1999 Elsevier Science B.V. All rights reserved. Keywords: Fungal urinary tract infection; Systemic antifungals; High-risk patients
1. Introduction The incidence of candiduria and fungal urinary tract infections (UTI) has increased in recent years. Risk factors comprise the extensive use of broad-spectrum antimicrobial agents, corticosteroids, immunosuppressive agents, cytotoxic chemotherapy complicated by mucositis and neutropenia, elderly age, diabetes mellitus, structural or functional abnormalities of urinary tract with indwelling urinary catheter or nephrostomy. Increased incidence is also observed in chronic renal failure and hemodialysis patients. Renal transplant patients are at high risk for developing funguria and pyelonephritis due to immunosuppressive therapy [1– 3]. The most frequent organism causing fungal UTI is still Candida albicans followed by Candida (Torulopsis) glabrata, Candida tropicalis, and Candida krusei [1,4]. * Corresponding author. Tel.: + 421-7-373628; fax: + 421-7325754.
Non-albicans Candida and non-Candida yeasts are steadily increasing as the ethiological cause of fungal UTI [4]. In comparison with bacterial UTI, the diagnostic criteria of significant funguria and fungal UTI are not well established. Wise et al. [5] concluded that an increased risk of fungal pyelonephritis was associated with counts of greater than 15 000 CFU/ml. Other authors [6,7] defined the cut-off between colonization and infection as the lowest colony count from a single urine specimen to be 105 CFU/ml of fungal pathogen. In 5–15% of patients with symptomatic fungal UTI, funguria is accompanied by fungemia [4].
2. Patients and methods A total of 50 patients hospitalized in the years 1990– 1995 with fungal UTI were analysed. There were 26 males and 24 females with a mean age of 62.4 years. Inclusion criteria were cultural documentation of funguria (\ 105 CFU/ml), leucocyturia (\10/HPF ×400),
0924-8579/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved. PII: S 0 9 2 4 - 8 5 7 9 ( 9 9 ) 0 0 0 3 2 - 1
290
S. Krcmery et al. / International Journal of Antimicrobial Agents 11 (1999) 289–291
fever \38°C and typical symptoms of UTI (dysuria, frequent urination, lumbar pain or tenderness, etc.). Yeasts from urine were identified with API or Mycotube (Roche), and with Vitek Systems since 1993. Systemic antifungals (fluconazole, ketoconazole, itraconazole or amphotericin B) were used in all patients with regard to the type of isolated yeasts and their sensitivity patterns. All patients were analysed for risk factors, age and sex, renal function, presence of UTI complicating factors, spectrum of isolated yeasts, therapy and outcome. All patients were evaluated 3 – 10 days after the end of therapy (early follow-up) and 21 – 28 days after the end of therapy (late follow-up). Therapeutic success (cure) was defined as the resolution of clinical symptoms and sterile urine (funguria B103 CFU/ml). Persistent funguria ( ]103 CFU/ml) was recorded as therapeutic failure, even if no other signs or symptoms of infection were present. The x 2 test was used to check the comparability of patients characteristics. P values B 0.05 were considered significant.
3. Results The most frequent risk factors for development of symptomatic fungal UTI were: antibiotic therapy with more than one agent in the previous 7 days (96%), previous therapy with corticosteroids (72%), concomitant fungal infection or colonisation in a localisation other than the urinary tract (48%), indwelling urinary catheter or nephrostomy (46%), hematological malignancies with neutropenia (30%), structural or anatomical abnormalities of the urinary tract (26%), and diabetes mellitus (12%). Nine patients (18%) had significantly impaired renal function (mean serum creatinine 208 mmol/l). Only two of 50 patients did not receive any antimicrobials in the previous 7 days. Eighteen patients were previously treated with one antibiotic, 18 with two, and 12 with three or more antibiotics. Most frequently administered antimicrobial agents were third-generation cephalosporins (40 of 50 patients), and fluoroquinolones (33 of 50 patients). The distribution of yeasts isolated from urine prior to therapy is shown in Table 1. C. albicans was isolated from Table 1 Fungal urinary tract infections—isolated organisms Organism
Number of patients
Candida albicans Candida tropicalis Blastoschizomyces capitatus Candida krusei
36 5 5 4
Total
50
Table 2 Fungal urinary tract infections — antifungal chemotherapy Therapy
Cured
Failed
Total
n
%
n
%
n
%
Fluconazole Ketoconazole Itraconazole Amphotericin B
25 12 3 2
86.2 85.7 100.0 50.0
4 2 0 2
13.8 14.3 0.0 50.0
29 14 3 4
100 100 100 100
Total
42
84.0
8
16.0
50
100
36 patients, C. tropicalis and B. capitatus from five, and C. krusei from four patients, respectively. Only two patients had fungaemia. Simultaneous significant bacteriuria (] 105 CFU/ml) was present from 20 of 50 patients with fungal UTI (40%). Enterobacteriaceae were isolated in 12 patients, Pseudomonas aeruginosa from five and Enterococcus faecalis from three patients. Fluconazole was used in 29 patients (25 cured), ketonazole in 14 patients (12 cured), itraconazole in three patients (all cured) and systemic amphotericin B from four patients (two cured) (Table 2). In total, 42 of 50 patients (84%) were cured (32/36 with C. albicans and 10/14 with non-C. albicans associated funguria). Eight patients with fungal UTI died despite systemic antifungal therapy. There was no statistically significant difference between subgroups with regard to sex, renal function, etiology and treatment. There was no difference in number of deaths between C. albicans and non-C. albicans associated fungurias. All deaths except one were associated with terminal underlying disease and/or multiorgan failure. 4. Discussion It is widely accepted that patients with symptomatic fungal UTI require therapy. Cases of fungal pyelonephritis [8], papillary necrosis [9] and fungal bezoar formation [10] have been reported in the literature. Asymptomatic funguria in high-risk patients (e.g. renal transplant, obstructive uropathy, neutropenia, diabetes mellitus, immunocompromised patients) should also be treated [1,3,11]. If a urinary catheter or nephrostomy cannot be removed, the use of antifungal bladder irrigation should be considered. At present, amphotericin B is the most widely used agent for this type of treatment [12,13]. It appears that the irrigation is well tolerated without any serious adverse effects. Sanford [14] suggests that low amphotericin B concentrations (5–10 mg/l) may be efficacious and less toxic to the bladder mucosa. He recommends the administration of amphotericin B by triple-lumen catheter with cross-clamping for 60–90 min. Two days of irrigation with the above-mentioned concentration of the drug should be sufficient and adequate [1,14].
S. Krcmery et al. / International Journal of Antimicrobial Agents 11 (1999) 289–291
For systemic antifungal therapy, flucytosin nowadays plays a limited role in the treatment of fungal UTI due to its toxicity and marginal efficacy. The dose reduction in patients with compromised renal function is inevitable [2]. Ketoconazole is primarily eliminated via hepatic metabolism and only a small percentage of the drug is excreted in urine [1,3]. For the treatment of candiduria, recommended daily oral doses are 200 – 400 mg. Nevertheless, the eradication rates reported for the treatment of candiduria are approximately 60 – 65% [15,16]. Ketoconazole is associated with occasional gastrointestinal side-effects, hepatotoxicity and gynecomastia. It downregulates the P450 cytochrome enzyme system and interacts with drugs (including cyclosporine) metabolised through this system [3]. Fluconazole, a triazole antifungal agent, has a high oral bioavailability (\ 90%), long half-life (\ 30 h) and is primarily excreted unchanged in urine (80%), resulting in adequate urinary drug concentrations to treat candiduria [1,2]. It is effective against C. albicans and against the most common non-albicans Candida species, although higher doses may be required for infections caused by C. glabrata [17]. Infections caused by C. krusei should not be treated with fluconazole. Recommended daily doses are 200 – 400 mg (orally or i.v.) with the dosing interval of 24 h. Fluconazole is generally well tolerated and dose reduction should be considered in patients with chronic renal failure [1,17]. Systemic administration of amphotericin B should be reserved for severe systemic fungal infections caused by resistant yeasts. Only about 3% of an i.v. dose of the drug is excreted unchanged in the urine; however, it is associated with an extensive tissue distribution [1]. Liposomal amphotericin is an effective alternative in patients who are at risk for nephrotoxic side-effects, although it is unlikely that patients with renal insufficiency would achieve sufficient urinary levels of amphotericin B to treat funguria effectively [1,3]. Itraconazole, a new antifungal agent, is renally excreted only in about 35% and has practically no advantages over fluconazole in the treatment of fungal UTI [2]. The usual daily oral dose is 200 – 400 mg. Itraconazole is not dialysable and there is no need to change the dosing in renal failure.
5. Conclusions Fungal UTIs in severely ill patients represent a highrisk event. Yeast isolation and sensitivity testing in these patients is helpful in finding the optimal antifungal chemotherapy. Our results confirmed good efficacy of systemic antifungal chemotherapy in high-risk patients with fungal UTI. Patients with documented candiduria
291
should have their urinary catheters removed, if possible. Treatment of asymptomatic and low-risk patients is not required. These patients should be re-cultured and observed after the urinary catheter has been removed. The preferred therapy for symptomatic and high-risk patients without catheter or after its removal, is fluconazole. If the urinary catheter cannot be removed, amphotericin B bladder irrigation for 2–3 days should be considered. In patients with persistent funguria after treatment, complicating factors (obstructive uropathy, stones, etc.) have to be ruled out. Future studies should evaluate the efficacy of new antifungal agents and long-term antifungal prophylaxis in high-risk patients.
References [1] Guglielmo BJ, Stoller ML, Jacobs RA. Management of candiuria. Int J Antimicrob Agents 1994;4:135 – 9. [2] Kraatz G. Therapie der Pilzinfektion. Nieren- Hochdruckkr 1996;25:572 – 4. [3] Krcmery S. Urinary tract infections in renal transplant patients. In: Bergan T, editor. Urinary tract infections. Basel: Karger, 1997:48 – 52. [4] Oravcova E, Lacka J, Drgona L, et al. Funguria in cancer patients: analysis of risk factors, clinical presentation and outcome. Infection 1996;24:319 – 23. [5] Wise GJ, Goldberg P, Kozinn PJ. Genitourinary candidosis: diagnosis and treatment. J Urol 1976;116:778 – 80. [6] Gubbins PO, Piscitelli SC, Danzinger LH. Candidal UTI: A comprehensive review of their diagnosis and management. Pharmacotherapy 1993;13:110 – 6. [7] Ang BSP, Telenti A, King B, Sheckelberg MJ, Wilson WR. Candidemia from a urinary tract source. Clin Inf Dis 1993;17:662– 5. [8] Kauffman CA, Tan JS. Torulopsis glabrata renal infection. Am J Med 1974;57:217 – 24. [9] Knepshield JH, Feller HA, Leb DE. Papillary necrosis due to Candida albicans in renal allograft. Arch Intern Med 1968;122:441 – 4. [10] Irby PB, Stoller ML, McAninch JW. Fungal bezoars of the upper urinary tract. J Urol 1990;143:447 – 51. [11] Rubin RH. Infectious disease complications of renal transplantation. Kidney Int 1993;44:221 – 36. [12] Wise GJ, Kozinn PJ, Goldberg P. Amphotericin B as a urologic irrigant in the management of noninvasive candiduria. J Urol 1982;128:82 – 4. [13] Hsu CCS, Ukleja B. Clearance of Candida colonizing the urinary bladder by a two-day amphotericin B irrigation. Infection 1990;18:280 – 2. [14] 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 – 50. [15] Heel RC. Systemic candidosis and candiduria. In: Levine HB, editor. Ketoconazole in the management of fungal disease. New York: ADIS Press, 1981:115 – 8. [16] Graybill JR, Galgiani JN, Jorgensen JH, Strandberg DA. Ketoconazole therapy for fungal urinary tract infections. J Urol 1983;129:68 – 70. [17] Van’t Wout JW. Fluconazole treatment of candidal infections caused by non-albicans Candida species. Eur J Clin Microbiol Infect Dis 1996;15:238 – 42.