use of fluconazole as a local irrigant for nephrostomy tubes, The

Military Medicine, Mar 1999 by Clark, Max A, Gaunt, Tina, Czachor, John S

Objectives: Few data exist concerning the combined use of fluconazole systemically and as an irrigant for nephrostomy tubes in a patient with renal candidiasis. The patient described here presented with renal fungal balls obstructing the drainage of urine from her nephrostomy tubes. Methods: Twelve months after chemoradiation for a stage IIB squamous cell carcinoma of the uterine cervix, a 35-year-old woman presented with renal obstruction necessitating insertion of ureteral stents. After 6 months of chemotherapy, the patient developed uremia. After nephrostomy tubes were placed, renal candidiasis was noted, and fluconazole was begun systemically. When the renal candidiasis failed to clear, nephrostomy tube irrigations were begun. Results: Fourteen days of therapy with fluconazole resulted in the resolution of the uremia. The patient died 6 months later with her nephrostomy tubes in situ and without evidence of candidiasis in her urinary tract. Conclusions: The patient described was successfully treated without having to remove her nephrostomy tubes. Two other authors have reported the successful use of fluconazole irrigation to treat candidiasis in nephrostomy tubes that was unresponsive to systemic fluconazole. Before the appearance of these reports, the best results were obtained with removal of the catheter in renal candidiasis.

Introduction

Candida albicans is most commonly found in the gastrointestinal tract and the vagina as a nonpathogen. However, in certain circumstances, Candida can be the origin of systemic disease. Predisposing factors include instances in which the patient's immune system is altered. These include malignancy, chemotherapy, immunosuppressive states, diabetes, and prolonged antibiotic therapy, all of which place patients at an increased risk of developing fungal infections. In some cases, these can be life-threatening. The urinary tract is a common site of involvement, especially in disseminated candidiasis. Infection can occur as primary renal candidiasis, refractory cystitis, or acute ureteral obstruction as a result of C. albicans fungal balls. 1-3

Kayla and Ahern have shown that yeast cells can become adherent to silicone tubing.4 They used silicone urethral catheters that were incubated for 24 hours with a known culture of Candida. The catheters were then flushed five times with 100 ml of saline and incubated a second time for 24 hours. They were flushed again and incubated a third time for 24 hours. Cells of C. albicans, C. tropicalis, and C. parapsilosis were noted to adhere to the catheters. The authors further noted that the adherent yeast cells were able to survive at median inhibitory concentrations of antifungal agents that exceeded those of nonadherent cells. This mechanism may explain why patients with long-term indwelling urinary devices may develop recalcitrant candidiasis.

Fluconazole is a bis triazole derivative that was developed for the treatment of localized and systemic fungal infections.5-7 Initially, it was developed for use in immunocompromised individuals.5,8 It has well established efficacy and has been found to be as effective as amphotericin B against C. albicans.6

Fluconazole is more effective than ketoconazole against Candida and Cryptococcus in vivo.6 It has been generally well tolerated, with only minor side effects, most commonly mild nausea, occasional vomiting, and elevated liver function tests. This is in contrast to amphotericin B, which can have major side effects, including chills, seizures, and severe nephrotoxicity. Fluconazole achieves rapid tissue levels regardless of the route of administration. Levels in the urinary tract can be 10 to 30 times the plasma concentration, whereas concentrations in the spinal fluid, joint fluid, saliva, blister fluid, and vaginal secretions are approximately the same as serum levels.3 There are reported cases in the literature of disseminated candidiasis in patients with ureteral obstruction secondary to fungal balls. In a report by Walzer and Bear, amphotericin B irrigation along with 5-flucytosine and parenteral amphotericin B were used to treat a patient who had undergone renal transplantation.9 These authors demonstrated that the combination of systemic and local antifungal therapy could result in the rapid clearing of obstructive uropathy secondary to fungal infections.9 Simsek et al. reported 20 cases of catheter-associated candiduria treated with fluconazole irrigation.10 Four of the patients were women and 16 were men. Four of the patients had disseminated cancer. Twelve patients had suprapubic catheters, and 8 patients had nephrostomy tubes. Using 10 mg of fluconazole in 50 ml of normal saline, all tubes were irrigated twice daily, clamping the tubes for 15 minutes with each flush. By the 6th day of treatment, 85% [17/20) of patients were free of Candida. Three patients (15%) died with positive cultures. Oliver et al. reported a single case of recalcitrant candiduria in a nephrostomy tube treated with catheter irrigation.11 The authors treated a 76-yearold female in renal failure who had renal-tract candidiasis with systemic fluconazole, administering 200 mg/d for 3 days, then reducing the dose to 100 mg/d because of renal failure. After 9 days, the patient still had Candida in the urine from the nephrostomy tube. On day 9, nephrostomy tube irrigation was begun by placing 10 mg of fluconazole in 100 ml of normal saline and infusing the solution into the nephrostomy tube over 12 hours for a period of 3 days. Subsequent cultures were negative for Candida The authors placed a ureteral stent and removed the nephrostomy tube and continued the patient on oral fluconazole at 100 mg/d for an additional 40 days. Six months after discharge, the patient was alive and well.