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Efficacy of amphotericin B in combination with flucytosine against flucytosine-susceptible or flucytosine-resistant isolates of Cryptococcus neoformans during disseminated murine cryptococcosis.
Antimicrob Agents Chemother. 2006 Jan; 50(1):113-20.AA

Abstract

Whether or not flucytosine should be administered to patients infected with Cryptococcus neoformans isolates found to be resistant to flucytosine in vitro remains a controversial issue. Thus, the efficacy of amphotericin B and flucytosine in combination was investigated by mortality and fungal burden studies in a murine model of disseminated cryptococcosis using two clinical isolates of Cryptococcus neoformans, one susceptible and one resistant (i.e., 64 microg/ml) to flucytosine. Amphotericin B was given intraperitoneally at 0.25 or 0.5 mg/kg/day, while flucytosine was given at 100 or 250 mg/kg/day orally. Treatment was started 24 h or day 6 after inoculation and continued for 5 days in fungal burden and mortality studies, respectively. The combination of amphotericin B at 0.5 mg/kg/day and flucytosine at 250 mg/kg/day was significantly more effective than monotherapies for reducing fungal burden in brain, spleen, and lungs after infection by the flucytosine-susceptible isolate and in brain and spleen for the flucytosine-resistant isolate. For the flucytosine-resistant isolate, the combination of amphotericin B at 0.5 mg/kg/day with flucytosine at 100 mg/kg/day was significantly better than monotherapies for reducing the fungal burden in the brain. Survival obtained after the combination of amphotericin B at 0.5 mg/kg/day and flucytosine at 250 mg/kg/day increased compared to that obtained with monotherapies for both isolates, but the difference was statistically significant only for the flucytosine-susceptible isolate. Antagonism was never observed. This study demonstrates the beneficial effect of the addition of flucytosine to amphotericin B against experimental disseminated cryptococcal infection even when the C. neoformans isolate is resistant to flucytosine.

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Authors+Show Affiliations

Schwarz P
Centre National de Référence Mycologie et Antifongiques, Unité de Mycologie Moléculaire, Institut Pasteur, CNRS FRE2849, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
Dromer F
No affiliation info available
Lortholary O
No affiliation info available
Dannaoui E
No affiliation info available

MeSH

Amphotericin BAnimalsAntifungal AgentsBrainCryptococcosisCryptococcus neoformansDisease Models, AnimalDrug CombinationsDrug Therapy, CombinationFlucytosineLung

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16377675

Citation

Schwarz, Patrick, et al. "Efficacy of Amphotericin B in Combination With Flucytosine Against Flucytosine-susceptible or Flucytosine-resistant Isolates of Cryptococcus Neoformans During Disseminated Murine Cryptococcosis." Antimicrobial Agents and Chemotherapy, vol. 50, no. 1, 2006, pp. 113-20.
Schwarz P, Dromer F, Lortholary O, et al. Efficacy of amphotericin B in combination with flucytosine against flucytosine-susceptible or flucytosine-resistant isolates of Cryptococcus neoformans during disseminated murine cryptococcosis. Antimicrob Agents Chemother. 2006;50(1):113-20.
Schwarz, P., Dromer, F., Lortholary, O., & Dannaoui, E. (2006). Efficacy of amphotericin B in combination with flucytosine against flucytosine-susceptible or flucytosine-resistant isolates of Cryptococcus neoformans during disseminated murine cryptococcosis. Antimicrobial Agents and Chemotherapy, 50(1), 113-20.
Schwarz P, et al. Efficacy of Amphotericin B in Combination With Flucytosine Against Flucytosine-susceptible or Flucytosine-resistant Isolates of Cryptococcus Neoformans During Disseminated Murine Cryptococcosis. Antimicrob Agents Chemother. 2006;50(1):113-20. PubMed PMID: 16377675.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy of amphotericin B in combination with flucytosine against flucytosine-susceptible or flucytosine-resistant isolates of Cryptococcus neoformans during disseminated murine cryptococcosis. AU - Schwarz,Patrick, AU - Dromer,Françoise, AU - Lortholary,Olivier, AU - Dannaoui,Eric, PY - 2005/12/27/pubmed PY - 2006/4/1/medline PY - 2005/12/27/entrez SP - 113 EP - 20 JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 50 IS - 1 N2 - Whether or not flucytosine should be administered to patients infected with Cryptococcus neoformans isolates found to be resistant to flucytosine in vitro remains a controversial issue. Thus, the efficacy of amphotericin B and flucytosine in combination was investigated by mortality and fungal burden studies in a murine model of disseminated cryptococcosis using two clinical isolates of Cryptococcus neoformans, one susceptible and one resistant (i.e., 64 microg/ml) to flucytosine. Amphotericin B was given intraperitoneally at 0.25 or 0.5 mg/kg/day, while flucytosine was given at 100 or 250 mg/kg/day orally. Treatment was started 24 h or day 6 after inoculation and continued for 5 days in fungal burden and mortality studies, respectively. The combination of amphotericin B at 0.5 mg/kg/day and flucytosine at 250 mg/kg/day was significantly more effective than monotherapies for reducing fungal burden in brain, spleen, and lungs after infection by the flucytosine-susceptible isolate and in brain and spleen for the flucytosine-resistant isolate. For the flucytosine-resistant isolate, the combination of amphotericin B at 0.5 mg/kg/day with flucytosine at 100 mg/kg/day was significantly better than monotherapies for reducing the fungal burden in the brain. Survival obtained after the combination of amphotericin B at 0.5 mg/kg/day and flucytosine at 250 mg/kg/day increased compared to that obtained with monotherapies for both isolates, but the difference was statistically significant only for the flucytosine-susceptible isolate. Antagonism was never observed. This study demonstrates the beneficial effect of the addition of flucytosine to amphotericin B against experimental disseminated cryptococcal infection even when the C. neoformans isolate is resistant to flucytosine. SN - 0066-4804 UR - https://www.unboundmedicine.com/medline/citation/16377675/Efficacy_of_amphotericin_B_in_combination_with_flucytosine_against_flucytosine_susceptible_or_flucytosine_resistant_isolates_of_Cryptococcus_neoformans_during_disseminated_murine_cryptococcosis_ DB - PRIME DP - Unbound Medicine ER -