Combined activity of amphotericin B and 5-fluorocytosine against Cryptococcus neoformans in vitro and in vivo in mice. 1975

J D Hamilton, and D M Elliott

The in vitro and in vivo activities of amphotericin B and 5-fluorocytosine (5-FC) alone and in combination were studied to determine possible drug interactions against two strains of Cryptococcus neoformans, one sensitive to 5-FC and one resistant to 5-FC. In vitro tube dilution studies demonstrated only additive effects with the 5-FC-sensitive organism but antagonism with eth 5-FC-resistant organism. A mouse model of cryptococcal meningitis allowed comparative drug trails in a new model for the detection of drug interactions. Drug combinations were no more effective against meningitis caused by the 5-FC-sensitive organism than the additive effects of the individual drugs. However, meningitis caused by the 5-FC-resistant Cryptococcus responded less to drug combinations than to either drug alone. Serum levels of amphotericin B and 5-FC were comparable in all groups. No evidence of toxicity from the drug combinations was found. No inhibition of development of resistance to 5-FC by the combination with amphotericin B was detected.

UI MeSH Term Description Entries
D008581 Meningitis Inflammation of the coverings of the brain and/or spinal cord, which consist of the PIA MATER; ARACHNOID; and DURA MATER. Infections (viral, bacterial, and fungal) are the most common causes of this condition, but subarachnoid hemorrhage (HEMORRHAGES, SUBARACHNOID), chemical irritation (chemical MENINGITIS), granulomatous conditions, neoplastic conditions (CARCINOMATOUS MENINGITIS), and other inflammatory conditions may produce this syndrome. (From Joynt, Clinical Neurology, 1994, Ch24, p6) Pachymeningitis,Meningitides,Pachymeningitides
D003453 Cryptococcosis Fungal infection caused by genus CRYPTOCOCCUS. C gattii Infection,C neoformans Infection,C. gattii Infection,C. neoformans Infection,Cryptococcus Infection,Cryptococcus Infections,Cryptococcus gattii Infection,Torulosis,Cryptococcus neoformans Infection,C gattii Infections,C neoformans Infections,C. gattii Infections,C. neoformans Infections,Cryptococcoses,Cryptococcus gattii Infections,Cryptococcus neoformans Infections,Infection, C gattii,Infection, C neoformans,Infection, C. gattii,Infection, C. neoformans,Infection, Cryptococcus,Infection, Cryptococcus gattii,Infection, Cryptococcus neoformans,Infections, C gattii,Infections, C. neoformans,Toruloses
D003454 Cryptococcus A mitosporic Tremellales fungal genus whose species usually have a capsule and do not form pseudomycellium. Teleomorphs include Filobasidiella and Fidobasidium. Torula
D003455 Cryptococcus neoformans A species of the fungus CRYPTOCOCCUS. Its teleomorph is Filobasidiella neoformans. Blastomyces neoformans,Debaryomyces neoformans,Filobasidiella neoformans,Lipomyces neoformans,Saccharomyces neoformans,Torula neoformans,Torulopsis neoformans,Cryptococcus neoformans var. grubii
D003596 Cytosine A pyrimidine base that is a fundamental unit of nucleic acids.
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D004352 Drug Resistance, Microbial The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS). Antibiotic Resistance,Antibiotic Resistance, Microbial,Antimicrobial Resistance, Drug,Antimicrobial Drug Resistance,Antimicrobial Drug Resistances,Antimicrobial Resistances, Drug,Drug Antimicrobial Resistance,Drug Antimicrobial Resistances,Drug Resistances, Microbial,Resistance, Antibiotic,Resistance, Drug Antimicrobial,Resistances, Drug Antimicrobial
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D005437 Flucytosine A fluorinated cytosine analog that is used as an antifungal agent. 5-Fluorocytosine,Alcobon,Ancobon,Ancotil

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