Assuntos
Antifúngicos/antagonistas & inibidores , Fungos/efeitos dos fármacos , Anfotericina B/antagonistas & inibidores , Antifúngicos/farmacologia , Azóis/antagonistas & inibidores , Relação Dose-Resposta a Droga , Resistência Microbiana a Medicamentos , Flucitosina/antagonistas & inibidores , Testes de Sensibilidade MicrobianaRESUMO
The antifungal activity of amphotericin B (AMB), mepartricin (MEPA), 5-fluorocytosine (5FC) and three imidazoles was tested in combination with each of four quinolones against 60 clinical yeast isolates. The inhibitory activity of AMB and MEPA was marginally enhanced by the azaquinolones, nalidixic acid (NAL) and enoxacin (ENO), but there was antagonism when combined with the fluorinated quinolones ciprofloxacin (CIP) and norfloxacin (NOR). All quinolones except NAL partially antagonised 5FC. Miconazole (MCZ), ketoconazole (KTZ) and itraconazole (ITZ) were each found to be synergistic with low concentrations of the quinolones, and also with high concentrations of NAL and ENO, but were strongly antagonised by high concentrations of CIP and NOR.
Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Quinolinas/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , 4-Quinolonas , Anfotericina B/antagonistas & inibidores , Anfotericina B/farmacologia , Anti-Infecciosos , Antifúngicos/antagonistas & inibidores , Candida albicans/efeitos dos fármacos , Ciprofloxacina/farmacologia , Combinação de Medicamentos , Enoxacino , Flucitosina/antagonistas & inibidores , Flucitosina/farmacologia , Mepartricina/antagonistas & inibidores , Mepartricina/farmacologia , Ácido Nalidíxico/análogos & derivados , Ácido Nalidíxico/farmacologia , Naftiridinas/farmacologia , Norfloxacino/farmacologiaRESUMO
Determination of the MIC of flucytosine for 16 wild isolates of Cryptococcus neoformans and Candida spp. in YNBG medium containing 10 mg/l cytosine demonstrated antagonism of fungistatic activity compared with that determined in YNBG alone. Determination of the MIC in YNBG containing 10 mg/l cytarabine showed no change in activity for 14 of the strains, an increase for one and a decrease for another. Determination of serum flucytosine concentrations in a patient receiving cytarabine simultaneously revealed therapeutic levels. Fluctuations in serum flucytosine concentrations were observed in samples taken before, during and after concurrent cytarabine therapy but these may have resulted from unstable renal function rather than in-vivo inactivation of flucytosine by cytarabine. These data do not support significant antagonism of the fungistatic activity of flucytosine by cytarabine.
Assuntos
Citarabina/farmacologia , Flucitosina/antagonistas & inibidores , Candida/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Citosina/farmacologia , Feminino , Flucitosina/sangue , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-IdadeRESUMO
The in vitro effect of 5-fluorocytosine on human and murine hematopoiesis was studied by means of soft-gel assays for erythroid and myeloid colony-forming cells. The drug consistently inhibited colony formation by granulocyte-monocyte and erythroid precursor cells. Clear effects were observable at concentrations of 5-fluorocytosine of 5 x 10(-5) M (6.5 micrograms/ml), and concentrations of 5 x 10(-4) M (65 micrograms/ml) caused approximately 90% inhibition of cloning of bone marrow myeloid colony-forming cells from mice and normal humans. Greater concentrations of 5-fluorocytosine were required to inhibit erythroid progenitors than to inhibit myeloid precursors. Uracil competitively reversed the toxicity of 5-fluorocytosine. Our data strongly suggest that the hematopoietic toxicity of 5-5-fluorocytosine is mediated through cellular metabolism of the drug. The reversal of mammalian, but not of fungal, cytotoxic effects of 5-fluorocytosine by uracil may have important clinical applications.
