In vitro interactions of micafungin with amphotericin B, itraconazole or fluconazole against the pathogenic phase of Penicillium marneffei.

OBJECTIVES: Penicillium marneffei infection is an important disease among human immunodeficiency virus patients in south-east Asia, including southern China. However, therapeutic strategies are limited. Combination regimens with synergistic drugs could provide additional options for treating penicilliosis. We evaluated the in vitro efficacy of combining micafungin with amphotericin B, itraconazole or fluconazole against the pathogenic yeast form of P. marneffei.

METHODS: Twenty isolates of P. marneffei were assayed. Drug interactions were assessed with the chequerboard technique using the CLSI (formerly the NCCLS) microdilution method (M27-A2) with minor modifications. The fractional inhibitory concentration index (FICI) was used to classify drug interactions. Results were interpreted as follows: synergy, FICI < or =0.5; no interaction, FICI >0.5 and < or =4.0; or antagonism, FICI >4.0.

RESULTS: The in vitro interactions of micafungin combined with itraconazole showed the highest percentage of synergic interaction (65%); for the micafungin/amphotericin B combination, 50% of the isolates had synergic interaction. Micafungin significantly enhanced the antifungal activity of amphotericin B and itraconazole against P. marneffei. Micafungin, however, did not enhance the activity of fluconazole and no synergism was observed with this combination. Antagonism was not detected for any of the antifungal combinations assayed.

CONCLUSIONS: The results of this study suggest that micafungin enhances the efficacy of itraconazole or amphotericin B in vitro and indicate that an echinocandin, such as micafungin, might have a potential role in combination therapy among patients infected with P. marneffei.