Abstract
Objectives: Zygomycosis is an uncommon but devastating disease with few therapeutic options. Calcineurin inhibitors and sirolimus (mTOR inhibitor), commonly used in transplant patients as immunosuppressives, have antifungal activity. They are known to demonstrate synergy with triazoles against certain fungi, though limited data exist about their activity against zygomycetes. Our aim was to study the in vitro interaction of posaconazole with calcineurin inhibitors and sirolimus against zygomycetes. Methods: Drug interactions were assessed with chequerboard dilution for posaconazole with calcineurin inhibitors and sirolimus according to the CLSI M38-A2 method for filamentous fungi. Twenty-eight clinical isolates were studied, including Rhizopus arrhizus, Rhizopus microsporus, Rhizomucor pusillus, Mucor sp., Cunninghamella bertholletiae, Myocladus corymbifera and Apophysomyces elegans. Combinations of posaconazole with tacrolimus, cyclosporin A or sirolimus were used. Experiments were performed in duplicate. Mean fractional inhibitory concentration indices were calculated. Results: Posaconazole with calcineurin inhibitors demonstrated consistent synergy against C. bertholletiae, M. corymbifera and A. elegans, whereas synergy or no interaction was primarily observed against R. arrhizus, R. microsporus, R. pusillus and Mucor. Antagonism was seen with the combination of posaconazole and sirolimus. Strain variability was noted among the same species. Conclusions: The clinical significance of these findings is unclear, but further studies are warranted given the potential for concomitant use of these agents in transplant patients treated for zygomycosis.
| Original language | English (US) |
|---|---|
| Article number | dkq020 |
| Pages (from-to) | 701-703 |
| Number of pages | 3 |
| Journal | Journal of Antimicrobial Chemotherapy |
| Volume | 65 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 3 2010 |
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Keywords
- Azole antifungals
- Fungal susceptibility
- Mucormycosis
ASJC Scopus subject areas
- Pharmacology
- Microbiology (medical)
- Infectious Diseases
- Pharmacology (medical)
Cite this
In vitro interaction of posaconazole with calcineurin inhibitors and sirolimus against zygomycetes. / Narreddy, S.; Manavathu, E.; Chandrasekar, P. H.; Alangaden, G. J.; Revankar, S. G.
In: Journal of Antimicrobial Chemotherapy, Vol. 65, No. 4, dkq020, 03.02.2010, p. 701-703.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - In vitro interaction of posaconazole with calcineurin inhibitors and sirolimus against zygomycetes
AU - Narreddy, S.
AU - Manavathu, E.
AU - Chandrasekar, P. H.
AU - Alangaden, G. J.
AU - Revankar, S. G.
PY - 2010/2/3
Y1 - 2010/2/3
N2 - Objectives: Zygomycosis is an uncommon but devastating disease with few therapeutic options. Calcineurin inhibitors and sirolimus (mTOR inhibitor), commonly used in transplant patients as immunosuppressives, have antifungal activity. They are known to demonstrate synergy with triazoles against certain fungi, though limited data exist about their activity against zygomycetes. Our aim was to study the in vitro interaction of posaconazole with calcineurin inhibitors and sirolimus against zygomycetes. Methods: Drug interactions were assessed with chequerboard dilution for posaconazole with calcineurin inhibitors and sirolimus according to the CLSI M38-A2 method for filamentous fungi. Twenty-eight clinical isolates were studied, including Rhizopus arrhizus, Rhizopus microsporus, Rhizomucor pusillus, Mucor sp., Cunninghamella bertholletiae, Myocladus corymbifera and Apophysomyces elegans. Combinations of posaconazole with tacrolimus, cyclosporin A or sirolimus were used. Experiments were performed in duplicate. Mean fractional inhibitory concentration indices were calculated. Results: Posaconazole with calcineurin inhibitors demonstrated consistent synergy against C. bertholletiae, M. corymbifera and A. elegans, whereas synergy or no interaction was primarily observed against R. arrhizus, R. microsporus, R. pusillus and Mucor. Antagonism was seen with the combination of posaconazole and sirolimus. Strain variability was noted among the same species. Conclusions: The clinical significance of these findings is unclear, but further studies are warranted given the potential for concomitant use of these agents in transplant patients treated for zygomycosis.
AB - Objectives: Zygomycosis is an uncommon but devastating disease with few therapeutic options. Calcineurin inhibitors and sirolimus (mTOR inhibitor), commonly used in transplant patients as immunosuppressives, have antifungal activity. They are known to demonstrate synergy with triazoles against certain fungi, though limited data exist about their activity against zygomycetes. Our aim was to study the in vitro interaction of posaconazole with calcineurin inhibitors and sirolimus against zygomycetes. Methods: Drug interactions were assessed with chequerboard dilution for posaconazole with calcineurin inhibitors and sirolimus according to the CLSI M38-A2 method for filamentous fungi. Twenty-eight clinical isolates were studied, including Rhizopus arrhizus, Rhizopus microsporus, Rhizomucor pusillus, Mucor sp., Cunninghamella bertholletiae, Myocladus corymbifera and Apophysomyces elegans. Combinations of posaconazole with tacrolimus, cyclosporin A or sirolimus were used. Experiments were performed in duplicate. Mean fractional inhibitory concentration indices were calculated. Results: Posaconazole with calcineurin inhibitors demonstrated consistent synergy against C. bertholletiae, M. corymbifera and A. elegans, whereas synergy or no interaction was primarily observed against R. arrhizus, R. microsporus, R. pusillus and Mucor. Antagonism was seen with the combination of posaconazole and sirolimus. Strain variability was noted among the same species. Conclusions: The clinical significance of these findings is unclear, but further studies are warranted given the potential for concomitant use of these agents in transplant patients treated for zygomycosis.
KW - Azole antifungals
KW - Fungal susceptibility
KW - Mucormycosis
UR - http://www.scopus.com/inward/record.url?scp=77952572377&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952572377&partnerID=8YFLogxK
U2 - 10.1093/jac/dkq020
DO - 10.1093/jac/dkq020
M3 - Article
C2 - 20130026
AN - SCOPUS:77952572377
VL - 65
SP - 701
EP - 703
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
SN - 0305-7453
IS - 4
M1 - dkq020
ER -