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

L. T. Ganesan, Elias Kurian Manavathu, J. L. Cutright, G. J. Alangaden, P. H. Chandrasekar

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 - Jan 1 2004

Fingerprint

Echinocandins
Polyenes
Triazoles
Aspergillus fumigatus
caspofungin
Drug Combinations
Cell Survival
Itraconazole
Fungal Spores
Amphotericin B
Drug Interactions
In Vitro Techniques
nikkomycin
Growth
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

In-vitro activity of nikkomycin Z alone and in combination with polyenes, triazoles or echinocandins against Aspergillus fumigatus. / Ganesan, L. T.; Manavathu, Elias Kurian; Cutright, J. L.; Alangaden, G. J.; Chandrasekar, P. H.

In: Clinical Microbiology and Infection, Vol. 10, No. 11, 01.01.2004, p. 961-966.

Research output: Contribution to journalArticle

Ganesan, L. T. ; Manavathu, Elias Kurian ; Cutright, J. L. ; Alangaden, G. J. ; Chandrasekar, P. H. / In-vitro activity of nikkomycin Z alone and in combination with polyenes, triazoles or echinocandins against Aspergillus fumigatus. In: Clinical Microbiology and Infection. 2004 ; Vol. 10, No. 11. pp. 961-966.
@article{4e03151e2eb44dcfbeb96fa831a5e877,
title = "In-vitro activity of nikkomycin Z alone and in combination with polyenes, triazoles or echinocandins against Aspergillus fumigatus",
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.",
keywords = "Antifungal combination, Echinocandins, Fungicidal activity, Nikkomycin Z, Polyenes, Triazoles",
author = "Ganesan, {L. T.} and Manavathu, {Elias Kurian} and Cutright, {J. L.} and Alangaden, {G. J.} and Chandrasekar, {P. H.}",
year = "2004",
month = "1",
day = "1",
doi = "10.1111/j.1469-0691.2004.00996.x",
language = "English (US)",
volume = "10",
pages = "961--966",
journal = "Clinical Microbiology and Infection",
issn = "1198-743X",
publisher = "Elsevier Limited",
number = "11",

}

TY - JOUR

T1 - In-vitro activity of nikkomycin Z alone and in combination with polyenes, triazoles or echinocandins against Aspergillus fumigatus

AU - Ganesan, L. T.

AU - Manavathu, Elias Kurian

AU - Cutright, J. L.

AU - Alangaden, G. J.

AU - Chandrasekar, P. H.

PY - 2004/1/1

Y1 - 2004/1/1

N2 - 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.

AB - 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.

KW - Antifungal combination

KW - Echinocandins

KW - Fungicidal activity

KW - Nikkomycin Z

KW - Polyenes

KW - Triazoles

UR - http://www.scopus.com/inward/record.url?scp=9444248159&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9444248159&partnerID=8YFLogxK

U2 - 10.1111/j.1469-0691.2004.00996.x

DO - 10.1111/j.1469-0691.2004.00996.x

M3 - Article

C2 - 15521997

AN - SCOPUS:9444248159

VL - 10

SP - 961

EP - 966

JO - Clinical Microbiology and Infection

JF - Clinical Microbiology and Infection

SN - 1198-743X

IS - 11

ER -