Emergence of resistance to amphotericin B during therapy for Candida glabrata infection in an immunocompetent host.

Resistance in Candida species to amphotericin B, a polyene macrolide antimicrobial agent, is rare [1]. Almost all described cases of resistance to amphotericin B have occurred in immunocompromised hosts [1-4]. Additional risk factors include extensive chemotherapy with cytotoxic agents, granulocytopenia, and long-term treatment with both antibacterial and polyene antibiotics [1]. Primary resistance to amphotericin B has been described in immunocompetent patients who developed fungemia due to Candida lusitaniae [4] and Candida albicans [5] after receiving prolonged antibiotic therapy. Emergence of resistance to amphotericin B during therapy for infection due to C. albicans [1], C. lusitaniae [3], and Candida guilliermondii [6] has been documented in immunocompromised hosts. We report the in vivo development of amphotericin B resistance in an immunocompetent host infected with Candida glabrata. A 79-year-old woman with a 4-year history of calcium oxalate kidney stones developed recurrent urinary tract infections. She had a history of glucose intolerance (diet controlled) and stage I endometrial cancer for which she had undergone total abdominal hysterectomy; there was no history of chemotherapy or cirrhosis. She was seronegative for antibodies to HIV. After 1 year of recurrent urinary tract infections, the patient underwent retrograde ureterography and cystoscopy, which showed a left ureteral stricture and pus draining from the ureterovesical junction. A ureteral stent was placed. Within hours, she developed sepsis. Two cultures of blood and a culture of urine all yielded C. glabrata. She was treated with intravenous fluconazole (400 mg daily) for 7 days, and her condition clinically improved; therapy was then switched to oral fluconazole (100 mg daily). Fluconazole therapy was discontinued after several weeks, and her dysuria quickly recurred. Cultures of urine again yielded C. glabrata, and a study of the left renal pelvis with contrast medium given via nephrostomy showed multiple filling defects in the pelvis, which were consistent with mycetomas. Fluconazole therapy was restarted. Within days, amphotericin B (0.5 mg/[kg· d]) was substituted for fluconazole. However, the level of serum creatinine rose above 3.3 mg/dL after 10 days of therapy, so amphotericin B was discontinued and fluconazole therapy (l00 mg/d) was restarted. Her symptoms resolved, the mycetomas cleared, urine cultures became negative, and the patient's level of serum creatinine dropped to 0.8 mg/dL. Fluconazole was stopped after 6 weeks. Within 8 days, urine cultures yielded C. glabrata, and fluconazole therapy was immediately resumed. Seven weeks later, she developed