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

  1. L. T. Ganesan,
  2. E. K. Manavathu,
  3. J. L. Cutright,
  4. G. J. Alangaden,
  5. P. H. Chandrasekar

Article first published online: 21 OCT 2004

DOI: 10.1111/j.1469-0691.2004.00996.x

Issue

Clinical Microbiology and Infection

Clinical Microbiology and Infection

Volume 10, Issue 11, pages 961–966, November 2004

Additional Information

How to Cite

Ganesan, L. T., Manavathu, E. K., Cutright, J. L., Alangaden, G. J. and Chandrasekar, P. H. (2004), In-vitro activity of nikkomycin Z alone and in combination with polyenes, triazoles or echinocandins against Aspergillus fumigatus. Clinical Microbiology and Infection, 10: 961–966. doi: 10.1111/j.1469-0691.2004.00996.x

Author Information

  1. Division of Infectious Diseases, Department of Medicine, Wayne State University, Detroit, MI, USA

*E. K. Manavathu, Division of Infectious Diseases, Department of Medicine, Wayne State University, 427 Lande Building, 550 E. Canfield, Detroit, MI 48201, USA E-mail: aa1388@wayne.edu

Publication History

  1. Issue published online: 21 OCT 2004
  2. Article first published online: 21 OCT 2004
  3. Original Submission: 21 April 2003; Revised Submission: 17 March 2004; Accepted: 16 April 2004

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Keywords:

  • Antifungal combination;
  • echinocandins;
  • fungicidal activity;
  • nikkomycin Z;
  • polyenes;
  • triazoles

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.

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