In-vitro activity of nikkomycin Z alone and in combination with polyenes, triazoles or echinocandins against Aspergillus fumigatus

L. T. Ganesan, E. K. Manavathu, J. L. Cutright, G. J. Alangaden, P. H. Chandrasekar

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

The in-vitro activity of nikkomycin Z was investigated in combination with polyenes, triazoles or echinocandins against 20 clinical isolates of Aspergillus fumigatus with the fractional inhibitory concentration index (FICI) method. The drug interactions were classified as synergic (FICI ≤ 0.5), no interaction (FICI > 0.5, but FICI ≤ 4) or antagonistic (FICI > 4). The fungicidal activity of nikkomycin Z alone and in combination with a representative echinocandin (caspofungin or triazole (voriconazole) was also examined with time-kill experiments and fungal cell viability assays. Two-drug combinations of nikkomycin Z with amphotericin B (FICI 3.59 ± 0.57), amphotericin B lipid complex (FICI 3.95 ± 0.74), liposomal amphotericin B (FICI 3.62 ± 0.98), itraconazole (FICI 2.0 ± 0.0), voriconazole (FICI 1.07 ± 0.37), posaconazole (FICI 2.20 ± 0.44) or ravuconazole (FICI 1.76 ± 0.44) showed no interactions, but the pairwise combination of nikkomycin Z with caspofungin (FICI 0.22 ± 0.19) or micafungin (FICI 0.35 ± 0.27) showed synergic activity against A. fumigatus. Time-kill studies and fungal cell viability assays showed that neither nikkomycin Z nor caspofungin alone possessed fungicidal activity against A. fumigatus, whereas a combination of these two drugs at concentrations ≥2 mg/L (≥ 0.031 × the concentration of drug that produced no visible growth) killed germinated conidia within 24 h in a concentration-dependent manner. These data suggest that two-drug combinations of nikkomycin Z with echinocandins, but not with polyenes and triazoles, have a synergic effect against A. fumigatus.

Original languageEnglish (US)
Pages (from-to)961-966
Number of pages6
JournalClinical Microbiology and Infection
Volume10
Issue number11
DOIs
StatePublished - Nov 2004

Keywords

  • Antifungal combination
  • Echinocandins
  • Fungicidal activity
  • Nikkomycin Z
  • Polyenes
  • Triazoles

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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