Is terbinafine a good antifungal drug to combine with voriconazole or caspofungin? Study of the activity of double combinations against invasive clinical isolates of A. fumigatus

Ref ID: 5572

Author:

J. Guinea, T. Peláez, P. Muñoz, í“. Cuevas-Lobato, E. Bouza

Author address:

Madrid, ES

Full conference title:

16th European Congress of Clinical Microbiology and Infectious Diseases

Abstract:

Objectives: Treatment of invasive aspergillosis is complicated by high toxicity and poor response.
Double-drug combinations are promising, but in vitro studies are necessary. We studied the activities of
voriconazole (VCZ, Pfizer), caspofungin (CAS, MSD) and terbinafine (TERB, Novartis) alone and
combined against clinical isolates of A. fumigatus in order to evaluate the potential of the combination of
TERB with the other two antifungal drugs.
Methods: We studied 10 strains of Aspergillus fumigatus from 10 hospitalized patients with proven
invasive aspergillosis (Ascioglu, CID 2002). Drug combinations were tested by using the guidelines
presented in document NCCLS M-38A, as modified for a broth microdilution checkerboard procedure. The
MIC for each drug was defined as the lowest concentration of antifungal drug that produced a complete
visual inhibition of fungal growth. Interactions between the drugs were studied by calculating the fractional
inhibitory concentration index (FICI) and interpreted as synergy (FICI < 0.5), antagonism (FICI > 4) and
indifference (FICI between 0.5 and 4). We calculated the MIC instead of the MEC for CAS in order to
compare the results with VCZ and TERB.
Results: The MIC90s and ranges of VCZ, CAS and TERB, in microg/ml, were: 1 (0.25-1), >4 and 4 (2- >
4) respectively. VCZ was the most active antifungal drug presenting the lowest MICs. The combination
VCZ-TERB proved to be synergistic in 90% of the strains (FICIs between 0.031 and 0.122). The
combination VCZ-CAS presented synergy in 10% of the strains (FICI 0.251), and the combination CASTERB
was indifferent for all strains. Antagonism was not present in any strain or combination. The strain
that showed indifference in the combination VCZ-TERB, also presented indifference in the other two
combinations.
Conclusions: The in vitro combination of terbinafine with voriconazole is synergistic against clinical
strains of Aspergillus fumigatus. In vivo studies are warranted.

Abstract Number: P744

Slides: y

Conference Year: 2006

Link to conference website: NULL

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