Candida spp. with acquired echinocandin resistance, France, 2004-2010

Area of Science:

• Mycology
• Infectious Diseases
• Antimicrobial Resistance

Background:

• Echinocandin antifungal drugs are crucial for treating invasive Candida infections.
• Emergence of antifungal resistance, particularly to echinocandins, poses a significant clinical challenge.
• Fks mutations in the target enzyme are a known mechanism of echinocandin resistance.

Purpose of the Study:

• To characterize episodes of infection caused by echinocandin-resistant Candida species.
• To identify novel Fks mutations associated with acquired echinocandin resistance.
• To investigate the genetic relationship between pre- and post-treatment Candida isolates.

Main Methods:

• Genomic sequencing of Candida isolates to identify Fks mutations.
• Antifungal susceptibility testing (MIC determination) for echinocandins.
• Molecular typing to assess genetic relatedness of isolates from individual patients.

Main Results:

• Twenty episodes of infection involving echinocandin-resistant Candida species were identified.
• Diverse and previously undescribed mutations in the Fks gene were found in resistant isolates.
• In 12 patients, subsequent isolates exhibiting high echinocandin MICs were genetically related to initial isolates with wild-type Fks sequences, indicating in vivo resistance development.

Conclusions:

• Acquired echinocandin resistance in Candida spp. is mediated by diverse and novel Fks mutations.
• Caspofungin treatment can select for pre-existing or emerging Fks mutations, leading to treatment failure.
• Monitoring for resistance mechanisms is essential for effective management of invasive fungal infections.