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Frequently Asked Questions

Use of bladder irrigations for treatment of superficial bladder infections

Introduction

Use of irrigations for treatment of bladder infections has been a practice for many years. One of the earliest reports, published in 1960, described the use of amphotericin B as a bladder irrigation for monilial cystitis.1 Since that time, a variety of antimicrobial agents have been used as bladder irrigations. There are, however, few randomized, controlled trials available to document the efficacy, as well as safety, of this practice. The following provides a brief review of antimicrobial, antifungal, and antiviral agents used topically for treatment of superficial bladder infections or cystitis.

Literature review

Antivirals

Cidofovir is an antiviral agent indicated for treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome. 2 Cidofovir is usually given by intravenous infusion, at a dose of 5 mg/kg for induction and maintenance therapy. However, several case reports have described the use of cidofovir in the treatment of BK virus-associated interstitial and hemorrhagic cystitis. Bridges and colleagues reported the outcomes of a patient treated with cidofovir bladder irrigation for treatment of hemorrhagic cystitis following allogeneic stem cell transplant.3 On day 22 after transplantation, the patient developed asymptomatic hematuria; urine cultures were positive for BK virus. Hematuria worsened by day 49 and did not respond to a reduction in immunosuppressive therapy, continuous bladder irrigation, and hyperhydration. Cidofovir 5 mg/kg in 60 mL of normal saline was instilled over 15 minutes, and the catheter clamped for 1 hour. Improvement was seen within 3 days of cidofovir. A second dose of cidofovir was given 1 week later, with further improvement seen 1 week after the second cidofovir dose.

Cidofovir was also used to treat chronic interstitial cystitis.4 A patient with a 4-year history of symptoms of cystitis and evidence of polyomavirus infection was treated unsuccessfully with ciprofloxacin and leflunomide. Intravesical cidofovir, 375 mg per week, was given for 3 doses. Improvement was seen after the first 2 doses. Decreases in viral load for both BK virus and JC virus were noted. No information was given on the method of administration.

In a third report, 6 patients who received allogeneic stem cell transplants developed symptoms of cystitis with a positive urinalysis for BK virus. 5 Cidofovir was given at a dose of 5 mg/kg in 60 mL of normal saline and instilled for 1 hour. Cidofovir was repeated daily for 2 days for patients with an indwelling catheter. Otherwise the doses were repeated weekly. All 6 patients had some degree of response, ranging from resolution of symptoms after a single dose to resolution after 2 weekly doses.

Antibacterial agents

Gentamicin bladder irrigations have been used for prevention or treatment of bladder infections in children, adolescents, and adults with neuropathic bladder.6 Patients ranged in age from 4 months to 36 years, with a median age of 10 years. Gentamicin 14 mg in 30 mL of normal saline was instilled via a urinary catheter once or twice daily and allowed to remain in the bladder overnight or until the next scheduled catheterization. Gentamicin was dispensed in 30 mL unit dose syringes and stored frozen for up to 1 month. A 4-day stability was given when stored under refrigeration. Treatment was continued for a median of 90 days (range, 3 to 1095 days). Twenty-six percent of patients had breakthrough urinary tract infection during therapy. Serum gentamicin levels were low, not more than 0.4 mcg/mL in any patient.

Wood and colleagues described the use of a tobramycin continuous bladder irrigation for treatment of a urinary tract infection due to Enterobacter cloacae in a patient with acute renal failure (urine output approximately 100 mL/day).7 Tobramycin 40 mg in 1000 mL of sterile water was instilled at 42 mL/h. The serum tobramycin level was undetectable after 3 days. However, tobramycin was discontinued and the urinary catheter removed following a positive urine culture for Candida and mild bladder erosion.

Vancomycin was used as a continuous infusion to treat a urinary tract infection with methicillin-resistant Staphylococcus aureus (MRSA) in a 90-year-old nursing home resident.8 Vancomycin 1000 mg in 1000 mL of normal saline was instilled at 42 mL/h for 5 days. Urine cultures were repeated 2 days after vancomycin therapy ended and were negative for MRSA. Vancomycin serum levels were described as 'negligible'; however, the author recommended monitoring of serum levels in the event of enhanced absorption due to mucosal inflammation or increased bladder pressure.

A case report by Curtis and Biundo described the use of piperacillin as an irrigation for treatment of recurrent bladder infections.9 Previous oral therapies had failed due to intolerability by the patient. Piperacillin 500 mg in 50 mL of normal saline was given as an intermittent irrigation (instilled for 30 minutes) twice daily for 5 days. Treatment was considered successful based on resolution of symptoms.

Antifungals

A number of studies and reports have described the use of amphotericin as a bladder irrigation, however, there appears to be limited evidence for its efficacy.10 Tuon and colleagues conducted a meta-analysis of published trials with amphotericin B bladder irrigation. 11 Nine prospective trials were included in the analysis. The concentration of amphotericin ranged from 0.005 to 0.3 mg/mL, given as a continuous infusion (primarily as 50 mg per 1000 mL over 24 hours) or intermittently (primarily as 10 to 40 mg in 100 to 200 mL 3 times per 24 hours). For continuous infusions, rate of clearance of candiduria at 24 hours ranged from 70% to 100% for 50 mg per 1000 mL, with one report of 62% with a dose of 10 mg per 1000 mL. Longer durations were not always associated with a higher percentage of clearance. A 3-day irrigation resulted in 100% clearance of candiduria, while the rate of clearance reported with 7 days of treatment was 94%. Clearance rates were similar for intermittent therapy, ranging from 81% to 87%; one study reported a 30% clearance with 10 mg of amphotericin per100 mL.

In a small prospective study, Nesbit and colleagues compared 10 mg and 50 mg of amphotericin per 1000 mL of sterile water as a continuous infusion (42 mL/hr) for 72 hours.12 The study was stopped early due to a higher failure rate in the 10 mg amphotericin group. The authors reported 100% fungal eradication with 50 mg amphotericin compared with 67% in the 10 mg group.

Finally, Jacobs and colleagues compared oral fluconazole with amphotericin bladder irrigation in the treatment of fungal urinary tract infections in elderly patients.13 Amphotericin 25 mg per 500 mL of dextrose 5% was instilled continuously at 42 mL/h for 5 days; fluconazole was given orally as a 200 mg loading dose followed by 100 mg per day, or 50 mg per day for patients with reduced renal function. Rates of eradication of funguria were higher with amphotericin-96% versus 73% (p<0.05) at 2 days after treatment.

Summary

Although described in the literature, data on the efficacy of bladder irrigations for superficial bladder infections or cystitis are limited. The Infectious Diseases Society of America (IDSA) has published guidelines on the treatment of bacterial and fungal infections of the bladder, and do not recommend bladder irrigations as first-line therapy (see Table).14,15 Although local application of agents to avoid systemic exposure may be desirable, there are little data on effective concentrations, optimal duration of therapy, and best manner of administration (continuous vs. intermittent).

Table. IDSA recommendations for bladder irrigations.14,15

Guideline

Indication

Therapy

Irrigation

Concentration

IDSA treatment guidelines for candidiasis

Symptomatic candiduria

Oral fluconazole

Alternatives: Intravenous Amphotericin,

Oral flucytosine

Amphotericin bladder irrigation not routinely recommended (>90% response but high relapse rate), except for fluconazole-resistant Candida species (eg, C. glabrata or C. krusei) or treatment of urinary fungal mass (as adjunctive therapy).

Amphotericin 50 mg/1000 mL sterile water

IDSA treatment of catheter-associated urinary tract infections in adults

Catheter-associated infections-prevention or treatment

Povidone-iodine

Chlorhexidine

Neomycin/ polymyxin

Data insufficient regarding bladder irrigations with antimicrobial agents in patients with indwelling catheters.

Some efficacy has been seen in preventing catheter-associated bacteriuria in patients with short-term catheterization undergoing surgical procedures.

NA

IDSA = Infectious Diseases Society of America; NA = not available.

References

1. Goldman H, Littman H, Oppenheimer G, Glickman S. Monilial cystitis-effective treatment with instillations of amphotericin B. JAMA. 1960;174:359-362.

2. Vistide [package insert]. Foster City, CA: Gilead Sciences; 2000.

3. Bridges B, Donegan S, Badros A. Cidofovir bladder instillation for the treatment of BK hemorrhagic cystitis after allogeneic stem cell transplantation. Am J Hematol. 2006;81(7):535-537.

4. Eisen D, Fraser I, Sung L, Finlay M, Bowden S, OConnell H. Decreased viral load and symptoms of polyomavirus-associated chronic interstitial cystitis after intravesicular cidofovir treatment. Clin Infect Dis. 2009;48(9):e86-88.

5. Rao K, Shea T. Intravesicular cidofovir for the management of BK virus-associated cystitis. Biol Blood Marrow Transplant. 2009;15(5):391-392.

6. Defoor W, Ferguson D, Mashni S, et al. Safety of gentamicin bladder irrigations in complex urological cases. J Urol. 2006;175(5):1861-1864.

7. Wood G, Chapman J, Boucher B, et al. Tobramycin bladder irrigation for treating a urinary tract infection in a critically ill patient. Ann Pharmacother. 2004;38(7-8):1318-1319.

8. Hajjar R, Philpot C, Morley J. Continuous bladder irrigation with vancomycin for the treatment of methicillin-resistant Staphylococcus aureus. J Am Geriatr Soc. 1996;44(7):886-887.

9. Curtis L, Biundo B. Irrigation with piperacillin for the treatment of bladder infection. Int J Pharm Comp. 2001;5(3):195.

10. Drew R, Arthur R, Perfect J. Is it time to abandon the use of amphotericin B bladder irrigation? Clin Infect Dis. 2005;40(10):1465-1470.

11. Tuon F, Amato V, Filho S. Bladder irrigation with amphotericin B and fungal urinary tract infection-systematic review with meta-analysis. Int J Infect Dis. 2009;13(6):701-706.

12. Nesbit S, Katz L, McClain B, Murphy D. Comparison of two concentrations of amphotericin B bladder irrigation in the treatment of funguria in patients with indwelling urinary catheters. Am J Health-Syst Pharm. 1999;56(9):872-875.

13. Jacobs L, Skidmore E, Freeman K, Lipschultz D, Fox N. Oral fluconazole compared with bladder irrigation with amphotericin B for treatment of fungal urinary tract infections in elderly patients. Clin Infect Dis. 1996;22(1):30-35.

14. Hooton T, Bradley S, Cardenas D, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(5):625-663.

15. Nicolle L, Bradley S, Colgan R, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40(5):643-654.