In vitro activity of amphotericin B with fluconazole or voriconazole combinations against Candida albicans isolates

ÖZ Y., Aksit F., Kiraz N., Kiremitci A.

MIKROBIYOLOJI BULTENI, vol.42, no.1, pp.149-155, 2008 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 42 Issue: 1
  • Publication Date: 2008
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.149-155
  • Eskisehir Osmangazi University Affiliated: Yes


The aim of this study was to investigate the in vitro interaction of amphotericin B in combination with fluconazole or voriconazole against Candida albicans clinical isolates by using a broth microdilution checkerboard assay and E-test. A total of 30 C.albicans strains isolated from blood, urine, sputum and pus samples were included to the study and the minimum inhibitory concentrations (MICs) of amphotericin B (AMB), fluconazole (FLU) and voriconazole (VOR) were determined by broth microdilution method and E-test. All strains tested for susceptibility were interpreted as susceptible by both methods (FLU MICs < 8 mu g/ml, VOR and AMB MICs < 1 mu g/ml). The rates of MIC agreement between two methods were as follows: AMB, 83%; FLU, 97%; VOR, 97%. AMB+FLU and AMB+VOR combinations were tested by checkerboard broth microdilution and E-test methods. The combination test results were determined by using the fractional inhibitory concentration (FIC) index as synergistic, indifferent or antagonistic. AMB+FLU combination tested by checkerboard broth microdilution revealed synergy in one strain (3.3%) and antagonism in none, while the same combination tested by E-test revealed synergy in two (6.6%) and antagonism in four (13.3%) strains. The strains which exhibited synergy were different from eachother in two assays. This combination led to indifferent results in 23 (76.6%) of the strains. On the other hand AMB+VOR combination yielded synergistic results in two (6.6%) strains by both of the methods, however, these two strains were again different from eachother. No antagonism was detected by AMB+VOR combination while the combination was indifferent in 26 (86.6%) of the strains. Agreement between the checkerboard and E-test results was 87%. Although significant synergy was not detected in AMB+azole combinations, it was yet hopeful to obtain no antagonism. However, multi-center, large-scale, well standardized in-vitro and clinical studies about AMB and azole interaction which is a matter of debate, are necessary.