Sustaining Treatment of Coccidioidal Meningitis by Extending the Stability of Amphotericin B

Abstract

Coccidioides immitis is an endemic fungus in California's San Joaquin Valley. The most debilitating and life-threatening manifestation is meningitis. The administration of intrathecal amphotericin B is an effective treatment, without which mortality is almost certain within 1 year. Kern Medical Center currently prepares 600 intrathecal doses annually for patients who have failed treatment with high-dose oral fluconazole. The recent national amphotericin B shortage severely compromised this life-saving therapeutic modality.

Although a vial of amphotericin B reconstituted with sterile water for injection is stable in the refrigerator for 7 days, this extended period of use could subject a single vial to as many as 15 entries. To prevent contamination, our practice has been to discard the remaining amphotericin B after 24 hours. However, if the stability of admixed amphotericin B could be extended and its sterility ensured, our institution would be able to provide care during drug shortages. After reconstitution of a 50 mg amphotericin B vial with 10 mL of sterile water, a 1 mL aliquot was added to each of seven 50 mL bags of 5% dextrose in water, resulting in a concentration of 100 mcg/mL. Five 2 mL samples were obtained from each bag on days 0 and 15. Visual stability, concentration, pH, and sterility were measured. Our results indicate that an amphotericin B concentration of 100 mcg/mL is stable in 5% dextrose for 15 days when stored at 4° Celsius and protected from light.