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Candiduria: Should we treat, when and how?

Candiduria: Should we treat, when and how?. Hail M. Al-Abdely, MD Consultant Infectious Diseases King Faisal Specialist Hospital & Research Center. Presentation Outline. How common is this problem? Who gets it? Why do we get candiduria? Why should we treat it?

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Candiduria: Should we treat, when and how?

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  1. Candiduria: Should we treat, when and how? Hail M. Al-Abdely, MD Consultant Infectious Diseases King Faisal Specialist Hospital & Research Center

  2. Presentation Outline • How common is this problem? • Who gets it? • Why do we get candiduria? • Why should we treat it? • Who should be treated? and who should not? • How to treat candiduria? • What are the current recommendations in the management of candiduria?

  3. Funguria or Candiduria Candiduria = 99% of Funguria

  4. How common is Candiduria?

  5. How common is this problem? • 1910: Raffin was the first to report candiduria • 1946: first well-documented case of candiduria. Moulder MK. J Urol 1946, 56:420-426 • 1957: Cross-sectional study • Candiduria in only 15 of 1500 patients. • More than 50% of these 15 patients had diabetes mellitus and were receiving antibiotics. Guze LB, Harley LD: Yale J Biol Med 1957, 30:292–305 • 1972: In a prospective study of healthy adults • Urine cultures were positive in 10 of 440 • Culture results reverted to negative when clean catch techniques were used Schonebeck J, Ansehn S: Scand J Urol Nephrol 1972, 6:123–128

  6. How common is Candiduria? • From 1980-1990 the nosocomial fungal infection rate for urinary tract infections had risen from 9.0 to 20.5 per 10,000 hospitalized patients • Nosocomial bacteriuria or candiduria develops in up to 25% of patients requiring a urinary catheter for >7 days, with a daily risk of 5% • Candida species are now the commonest organisms isolated from urine specimens in surgical ICU patients. Maki DG, Tambyah PA. 2001 Emerg Infect Dis;7:342-7 Lundstrom T, Sobel J. Clin Infect Dis. 2001 ;32:1602-7

  7. Microbial pathogens causing nosocomial catheter-associated urinary tract infections in U.S. acute-care hospitals, 1990-92 Jarvis WR, Martone WJ. J Antimicrob Chemother 1992;29:19-24.

  8. Who gets Candiduria?

  9. Who gets it? • Diabetes mellitus • Antibiotics • Indwelling urinary catheters • Other risk factors.      • Extremes of age • Female sex • Immunosuppressive agents • Use of iv catheters • Interruption of the flow of urine • Radiation therapy Hamory BH. J Urol1978, 120:444-448 Platt R, et al. Am J Epidemiol1986, 124:977-985 Storfer SP, et al. Infect Dis Clin Pract1994, 3:23-29 Phillips JR. Pediatr Infec Dis1997, 16:190-194

  10. Clin Infect Dis 2000, 30:14–18

  11. Prospective Multicenter Surveillance Study of Funguria in Hospitalized Patients • Study design: • Prospective “observational” multicenter study • No attempt was made to influence physicians' responses to the report of a urine culture yielding yeast. • Patients were followed until their discharge from the hospital or for a maximum of 10 weeks. • Underlying conditions. • Urinary tract instrumentation. • Symptoms and signs of infection. • Urinalysis results. • Organisms isolated. • Treatment. • Outcomes.

  12. Underlying diseases or conditions in 861 patients with funguria. Kauffman CA, et al.Clin Infect Dis 2000, 30:14–18.

  13. Urinary drainage devices in and procedures undergone by 861 patients with funguria Kauffman CA, et al.Clin Infect Dis 2000, 30:14–18.

  14. Initial yeast isolates from urine 861 patients with funguria Kauffman CA, et al.Clin Infect Dis 2000, 30:14–18.

  15. Why do we get candiduria?

  16. Why do we get candiduria? • Defense mechanisms against development of candiduria? • Flushing effect of urine • Normal urinary tract anatomy • Normal urinary tract function • Balanced distribution of perineal flora • Causes of breach of defense mechanisms?

  17. Routes of entry of uro-pathogens to catheterized urinary tract Maki DG, Tambyah PA. 2001 Emerg Infect Dis;7(2):342-7

  18. Scanning electron micrograph of an infected catheter showing dense and complex biofilm on the extraluminal surface Maki DG, Tambyah PA. 2001 Emerg Infect Dis;7(2):342-7

  19. Stark RP, Maki DG. N Engl J Med 1984;311:560-4.

  20. Why should we treat Candiduria?

  21. Why should we treat it? • Symptomatic UTI • Ascending infection. • Invasive cystitis • Pyelonephritis • Fungus ball • Hematogenous spread. • Invasive candidiasis/candidemia • Candiduria as the only sign of invasive candidiasis/candidemia

  22. mycoses 42, 285–289 (1999)

  23. Antifungal therapy for 861 patients with funguria Kauffman CA, et al.Clin Infect Dis 2000, 30:14–18.

  24. Who is at risk of invasive candidiasis from candiduria • Patients with neutropenia • Infants with low birth weight • Patients with renal allograft • ICU patients with multiple site colonization • Patients who will undergo urologic manipulations • Patients with significant urinary tract obstruction

  25. Why should we not treat it?

  26. Why should we not treat it? • Candiduria is discovered, rather than detected by deliberate research • Problems with diagnosis • Contamination: • Urine specimens become contaminated with Candida during the process of obtaining a urine • Vulvo-vestibular colonization with Candida (10% 65%) • Colonization of the drainage device • No reliable method for differentiating colonization from infection. • Asymptomatic adherence and settlement of yeast may result in a high concentration of the organisms on urine culture • Infection • Tissue invasion can not be determined • Pyuria and colony counts • Problems with outcome of Treatment • Benefits versus risks

  27. Significance of High Colony Counts and Pyuria Colony counts • 1956: Edward Kass defined significant bacteruria as 100,000 cfu/ml. Kass EH: Trans Assoc Am Physicians 1956, 69:56–64 • 1984: Stamm showed that cases of pyelonephritis and symptomatic cystitis had bacterial counts <100,000. Stamm WE:Eur J Clin Microbiol 1984, 3:279–281. • Problems: • These definitions were conducted with E. coli • Never obtained for patients with urinary catheters • Never done with candida • Ability candida grow fast in urine can give high counts even from contaminated specimen

  28. Significance of High Colony Counts and Pyuria • Indicates “inflammation” along the urinary tract • Coupled with significant colony count indicates “infection”. • Problems: • Catheter irritation can cause pyuria and hematuria • Co-existing bacterial pathogen is common Pyuria

  29. Outcome of funguria in 530 patients for whom outcome was documented Kauffman CA, et al.Clin Infect Dis 2000, 30:14–18

  30. Candidemia in 861 patients with Funguria • Candidemia found in 7 (1.3%) patients • All had intravascular catheters and multiple underlying diseases • Five of 7 patients with candidemia died • Two patients (0.4%) died because of candidiasis Kauffman CA, et al.Clin Infect Dis 2000, 30:14–18.

  31. Sobel JD, et al.: Clin Infect Dis 2000, 31:209–210

  32. Patients have 2 consecutive positive urine cultures for yeast that were performed at least 24 h apart • Candiduria was defined as the presence in both cultures of >1000 cfu/Ml. • Catheterized patients were eligible only if a follow-up culture was positive after removal or replacement of the catheter. • Asymptomatic candiduria was defined as absence of both urinary symptoms and fever • Patients were stratified by catheterization status • Treatment 400mg loading followed by 200mg QD for 13 days • Urine cultures done at days 3, 7 & 14 and 2 wks after the end of Rx

  33. Sobel JD, et al.: Clin Infect Dis 2000, 30:19-24

  34. Sobel JD, et al.: Clin Infect Dis 2000, 30:19-24

  35. Sobel JD, et al.: Clin Infect Dis 2000, 30:19-24

  36. Mortality • 12 in fluconazole group and 14 in placebo group (P=0.69) • No mortality was attributed to fungal infection or treatment • No cases of candidemia Sobel JD, et al.: Clin Infect Dis 2000, 30:19-24

  37. How to treat candiduria?

  38. How to treat candiduria? • Modify risk factors • Medical therapy

  39. Adopted from: Fisher JF. Curr Infect Dis Reports 2000, 2:523-530

  40. Medical Therapy Polyenes Amphotericin B (deoxycholate) - 1958 Liposomal amphotericin B (AmBisome) - 1997 Amphotericin Lipid Complex (ABLC) - 1996 Amphotericin Colloidal Dispersion (ABCD) - 1996 Azoles Miconazole (intravenous) - 1979 Ketoconazole (P.O) - 1981 Fluconazole (P.O, intravenous) - 1990 Itraconazole (capsule, solution, intravenous) – 1992 Voriconazole (P.O, intravenous)-2002 Others Griseofulvin - 1959 5-Flucytosine - 1972 Terbinafine – 1996 Caspofungin- 2001

  41. Common, benign. Fluc safe and effective. Infrequent iv Am B is safe. Rx: FLUC, bladder irrigation Iv Am B Slightly more common but benign, treatment toxic (Am B, 5-FC). No Rx More common but benign in most patients, imidazoles are not effective. Am B toxic, Rx: Bladder irrigation with Am B Candiduria revisited. Era of EBM Rx: Selective therapy candiduria uncommon and benign, NO Rx 1960s 1970s 1980s 1990s 2000 Evolution of Treatment of Candiduria

  42. Medical Therapy of Candiduria (1) • Azoles • Fluconazole • Advantage: Safe, high concentration in urine and effective when compared with other therapies • Disadvantage: Limited spectrum because of resistance. Effect is short-term • Itraconazole: • Advantage: broad-spectrum • Disadvantage: Unfavorable pharmacokinetics, no concentration in urine, limited data showed failures • Ketoconazole: • More or less like itraconazole • Voriconazole: • Advantage: broad-spectrum • Disadvantage: No data on efficacy

  43. Medical Therapy of Candiduria (2) • Amphotericin B-based • Intravenous AmB deoxycholate • Advantage: Broad-spectrum, prolonged concentration in urine • Disadvantage: toxicity • Topical AmB deoxycholate (bladder irrigation): • Advantage: broad-spectrum, low toxicity • Disadvantage: Local therapy of the bladder • Lipid formulations of AmB: • Advantage: broad-spectrum, low toxicity • Disadvantage: No concentration in urine. Reports of many failures

  44. Medical Therapy of Candiduria (3) • Others • 5-Flucytosine • Advantage: High concentration in urine, covers non-albicans Candida • Disadvantage: Resistance and toxicity • Caspofungin: • Advantage: broad-spectrum • Disadvantage: No data • Terbinafine: • No data

  45. Medical Therapy of Candiduria (4) • The main therapeutic modalities • Systemic Fluconazole • Variable duration • Systemic Amphotericin B • Short duration • Topical Amphotericin B (Bladder irrigation) • Short duration • Continuous • Intermittent with catheter clamping

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