Is It Time for Systematic Voriconazole Pharmacogenomic Investigation for Central Nervous System Aspergillosis?

Abstract

Voriconazole is the standard treatment for invasive aspergillosis but requires therapeutic drug monitoring to optimize therapy. We report two cases of central nervous system aspergillosis treated with voriconazole. Because of low trough plasma concentrations, we identified gain-of-function mutations in CYP2C19 that were partially responsible for the therapeutic failure of voriconazole. We suggest that systematic voriconazole pharmacogenomic investigation of cerebral aspergillosis be performed to avoid effective therapy delay in this life-threatening disease.

• Authors: François Danion, Vincent Jullien, Claire Rouzaud, Manal Abdel Fattah, Simona Lapusan, Romain Guéry, Naïke Bigé, Marjolaine Morgand, Nicolas Pallet, Fanny Lanternier, Olivier Lortholary
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 62 Issue 9 (09 2018) ISSN: 1098-6596 [Electronic] United States
• PMID: 29967027 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2018 American Society for Microbiology.

Chemical References

• Antifungal Agents
• Cytochrome P-450 CYP2C19
• Voriconazole

Topics

• Adult
• Aged
• Antifungal Agents (therapeutic use)
• Aspergillosis (drug therapy, genetics)
• Central Nervous System (microbiology)
• Cytochrome P-450 CYP2C19 (genetics)
• Drug Monitoring (methods)
• Female
• Humans
• Mutation (genetics)
• Pharmacogenetics (methods)
• Voriconazole (therapeutic use)