In Vivo and in Vitro Antifungal Effects of Chlorhexidine in Combination with Posaconazole, Itraconazole or Voriconazole against Scedosporium/Lomentospora

Abstract

Background: Scedosporium/Lomentospora species are filamentous fungi that can cause a wide range of infections, but it is resistant to many clinical antifungal drugs. Therefore, alternative antifungal drugs need to be found. Objective: The present investigation endeavored to ascertain the in vitro and in vivo efficacy of chlorhexidine (CHX) and azoles against fungi. Methods: The checkerboard method was used to determine the sensitivity of drugs against 16 Scedosporium/Lomentospora strains in in vitro experiments. The combined antifungal effect of CHX with itraconazole (ITR), voriconazole (VOR), and posaconazole (POS) against Scedosporium/Lomentospora species was tested in vivo with Galleria mellonella larvae. Results: In vivo tests showed that none of the examined strains was significantly affected by CHXs antifungal properties, but satisfactory synergistic effect was observed in vitro when CHX was combined with ITR, VOR, or POS against 13 (81.25%), 11 (68.75%), and 13 (81.25%) strains, respectively. Moreover, the minimum inhibitory concentration (MIC) ranges of CHX combined with azoles against Scedosporium and Lomentospora decreased significantly (p < 0.05). No antagonism was observed in any combination. Experiments in vivo showed that CHX combined with an azole (except for ITR) significantly increased the survival rate of G. mellonella larvae and considerably reduced the number of fungal clusters in infected tissues. Conclusions: The combinations of CHX and azoles enhanced the antimicrobial activity of these agents against Scedosporium/Lomentospora species, indicating potential for preventing azole resistance. However, the in vivo antimicrobial effect of the combination of CHX and ITR did not achieve ideal effects.