Desde 1953, anfotericina B (AnB) tem sido usada como droga de escolha no tratamento de micoses profundas. No entanto, a alta capacidade desta droga de provocar graves reações adversas, especialmente nefrotoxicidade, fez com que pesquisadores procurassem outros regimes de terapia na busca da cura destas infecções. Estudos prévios demonstraram sinergismo na combinação das drogas AnB e um derivado nitroimidazóico ativo contra bactérias anaeróbias e protozoários, metronidazol (Me) no tratamento de candidíase sistêmica experimental. O intuito deste experimento foi estudar a ação da AnB, utilizando-se metade da dose usual, associada a Me para tratar infecção por Candida albicans, em camundongos da espécie BALB/c, analisando os seguintes parâmetros: alteração do aspecto tisico dos animais, como perda de peso; tempo de sobrevida, aspecto tecidual dos rins e recuperação de leveduras a partir deste órgão. Os animais foram inoculados com 4,2 X 10⁶ células/ml de C. albicans. Os camundongos não tratados tiveram morte, em média, no 10° dia após inoculação. Os camundongos que tiveram tratamento convencional com AnB (0,5mg/kg) apresentaram sérias lesões no tecido renal observadas por análise histopatológica, em que foram evidenciadas nefrose tóxica. Os animais tratados com a metade da dose (0,25 mg/kg) não apresentaram cura total da enfermidade, obtendo sobrevida média de 23 dias. O tratamento com a associação de AnB na metade da dose usual (0,25mg/kg) com Me nas doses 22,5 mg/kg ou 11,25 mg/kg, mostrou ser mais eficaz que a monoterapia com AnB 0,25 mg/kg, promovendo aumento do tempo de sobrevida dos animais, como também diminuindo o número de colônias da levedura isoladas a partir dos rins desses camundongos. Foram observadas também que as lesões renais ocorridas no tratamento com a associação foram menores quando comparadas aos achados relativos à monoterapia. Devido a alta toxicidade da AnB, estes achados sugerem que a combinação entre as duas drogas pode ser um caminho na utilização de AnB de forma segura e eficaz.

Since 1953, amphotericin B (AnB) has been used as the drug of choice for the treatment of disseminated mycosis. However, its ability to cause serious side effects such as nephrotoxicity, has made researchers find other therapeutic regimes in order to treat these infections. Previous study has shown synergistic and additive interactions of amphotericin B and Metronidazole (Me), a nitroimidazole antiprotozoal agent in the treatment of disseminated candidiasis. The antifungal efficacy of the combination of these two drugs was evaluated in a mouse model of disseminated candidiasis caused by Candida albicans. Infection was achieved by intravenous inoculation with 4,2X10⁶ of yeast cells per ml via the lateral tail vein to 3 months old Balb/c mice. Deaths occurred in the 10^th day for untreated control group. Therapy schedule was divided into 3 doses with 24 h dosing interval, started on the 2^nd day following inoculation, and was continued on the 4^th and 6^th days. Groups of mice were treated with AmB alone at 0,5mg/kg and 0,25mg/kg of body weight, and in combination of AmB at 0,25mg/kg with Me at 22,5 and 11,25mg/kg of body weight. Efficacy were evaluated on the basis of comparison among the treatment groups with monotherapy and combined therapy, taking as parameter the viable counts of yeast cells from the right kidneys, in vivo outcomes, weight recovery and histopathologic analysis of kidneys. The group which was treated with monotherapy of AmB at conventional dose, 0,5mg/kg of body weight, has showed serious kidney lesions through histopathologic analysis. Mice treated with monotherapy of AmB at 0,25mg/kg of body weight couldn't recover from illness, and deaths occurred at day 23 on average. Treatment with the combination of the two drugs has showed to be more effective in comparison to AmB alone. AnB at 0,25mg/kg of body weight in combination with Me at 22,5 or 11,25mg/kg of body weight prolonged survival, and reduced tissue yeast counts from kidneys. The combination therapy also promoted an increase in extension of kidney lesion showed by histopathologic analysis. Given to the high toxicity of Amb, these findings suggest that the combination of these two drugs may be a way of using Amb safely and effectively.