Failure of a lipid based preparation of amphotericin B in the treatment of cryptococcus neoformans infection

Siddiqui J, Chang D, Jhatakia S, Sallenave C, Fitzgerald F

Author address: 

University of California Davis, Sacramento USA

Abstract: 

Introduction: Cryptococcus neoformans is encapsulated yeast that causes life threatening opportunistic infections in immunocompromised hosts. Currently, meningeal infection with Cryptococcus neoformans in patients with the human immunodeficiency virus / acquired immuno-deficiency syndrome [HIV/AIDS] is treated with either a triazole or a polyene in combination with flucytosine. With the advent of lipid based amphotericin B preparations, providers commonly use these drugs in order to minimize the drugs inherent toxicity. We report a case in which the use of a lipid based preparation likely resulted in poor penetration into the patient’s ascetic fluid resulting in a persistent nidus of infection. Clinical Problem: An HIV/AIDS patient with Cryptococcus neoformans fungemia, meningitis and peritonitis. Clinical Approach: In order to limit drug-induced toxicity the patient was treated with a lipid based amphotericin B preparation [Ambisome] in combination with flucytosine. Patient outcome: A 33-year-old man with HIV/AIDS was admitted for the evaluation of a new onset of fever, ascites and anasarca. On hospital day five the patient’s blood, cerebral spinal fluid and ascites fluid indicated the presence of yeast later identified as Cryptococcus neoformans. Treatment was initiated with Ambisome [3mg/kg/day] in combination with Flucytosine [100mg/kg/day]. Despite combination anti-fungal therapy, the patient’s clinical condition continued to deteriorate with blood and ascitic fluid cultures persistently growing Cryptococcus neoformans. Do to a worsening clinical condition and a lack of response to therapy, the patient was placed on comfort care by his family and died on hospital day 21. Conclusion: The failure of combination antifungal therapy against a susceptible organism has led us to the conclusion that the patient harbored a nidus of infection that was untreated by the lipid based preparation of amphotericin B. We believe that due to the lack of penetration of Ambisome into acetic fluid, the patient maintained an untreated focus of infection that continued to seed his blood and was a cause for his failure to respond to therapy. Our conclusions are tempered by our inability to measure drug concentrations in both serum and ascites fluid. However, in our attempts to limit toxicity, we chose an agent that may have lacked effective penetration into ascites fluid. In an era of wide spread use of lipid based polyene products; we believe that clinicians should remain acutely aware of the possible variability in drug concentrations into various body compartments.
2005

abstract No: 

6

Full conference title: 

15th Annual Focus on Fungal Infections
    • FFI 15th (2005)