Azole resistance in Aspergillus species: promising therapeutic options

ABSTRACT

Introduction

Azoles are the first-line antifungal agents used for the treatment of Aspergillus infection. There is an increasing concern for azole resistance all over the world mainly from agricultural fungicide use. Choosing safe and effective antifungal regimens has become a challenge.

Areas covered

Here, the authors review the epidemiology, mechanisms, and detection of azole resistance along with management options for azole-resistant Aspergillus infection, including new antifungal agents under development.

Expert opinion

Routine global epidemiological surveillance is required to understand azole resistance prevalence. Azole-resistant Aspergillus infections are associated with high mortality. No good therapeutic options are currently available. High index of suspicion of resistance is required if a patient is not responding to 4–7 days of azole therapy, particularly in the areas of resistance. Susceptibility testing for Aspergillus is not routinely available in many parts of the world, which makes it difficult to diagnose azole resistance in Aspergillus infection. There are several new antifungal classes with novel mechanisms of action; clinical trials are ongoing.

KEYWORDS:

• Aspergillosis
• Aspergillus fumigatus
• Aspergillus infection
• azole resistance
• drug resistant Aspergillus
• new antifungal agents

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Article highlights box

• Azole resistance, primarily due to widespread use of azoles in agricultural fungicides, is increasing in Aspergillus fumigatus and other Aspergillus species.

• Better global epidemiologic data on the prevalence of azole-resistant Aspergillus are urgently needed.

• In areas of low prevalence of azole resistance in Aspergillus, effective azole or polyene is recommended as empiric therapy.

• In areas of high prevalence (≥10%) of azole resistance in Aspergillus, a polyene or a combination of azole with an echinocandin may be considered for empiric therapy.

• Rapid laboratory identification of azole-resistance in Aspergillus species is of clinical importance in refractory cases.

• Newer drugs effective against azole-resistant Aspergillus are of promise; clinical trials are ongoing.

Additional information

Funding

This manuscript was not funded.