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Review
. 2019 Jul 1;5(3):55.
doi: 10.3390/jof5030055.

Invasive Aspergillosis by Aspergillus flavus: Epidemiology, Diagnosis, Antifungal Resistance, and Management

Shivaprakash M Rudramurthy  1   2 , Raees A Paul  3 , Arunaloke Chakrabarti  3 , Johan W Mouton  4 , Jacques F Meis  5   6
Affiliations
Review

Invasive Aspergillosis by Aspergillus flavus: Epidemiology, Diagnosis, Antifungal Resistance, and Management

Shivaprakash M Rudramurthy et al. J Fungi (Basel). .

Abstract

Aspergillus flavus is the second most common etiological agent of invasive aspergillosis (IA) after A. fumigatus. However, most literature describes IA in relation to A. fumigatus or together with other Aspergillus species. Certain differences exist in IA caused by A. flavus and A. fumigatus and studies on A. flavus infections are increasing. Hence, we performed a comprehensive updated review on IA due to A. flavus. A. flavus is the cause of a broad spectrum of human diseases predominantly in Asia, the Middle East, and Africa possibly due to its ability to survive better in hot and arid climatic conditions compared to other Aspergillus spp. Worldwide, ~10% of cases of bronchopulmonary aspergillosis are caused by A. flavus. Outbreaks have usually been associated with construction activities as invasive pulmonary aspergillosis in immunocompromised patients and cutaneous, subcutaneous, and mucosal forms in immunocompetent individuals. Multilocus microsatellite typing is well standardized to differentiate A. flavus isolates into different clades. A. flavus is intrinsically resistant to polyenes. In contrast to A. fumigatus, triazole resistance infrequently occurs in A. flavus and is associated with mutations in the cyp51C gene. Overexpression of efflux pumps in non-wildtype strains lacking mutations in the cyp51 gene can also lead to high voriconazole minimum inhibitory concentrations. Voriconazole remains the drug of choice for treatment, and amphotericin B should be avoided. Primary therapy with echinocandins is not the first choice but the combination with voriconazole or as monotherapy may be used when the azoles and amphotericin B are contraindicated.

Keywords: Aspergillus flavus; amphotericin B resistance; azole resistance; epidemiological cut-off value; epidemiology; invasive aspergillosis; molecular typing; treatment.

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Conflict of interest statement

S.M.R., R.A.P., A.C., and J.W.M. have no potential conflicts of interest to declare. J.F.M. received grants from F2G and Pulmozyme. He has been a consultant to Scynexis and Merck and received speaker’s fees from United Medical, TEVA, and Gilead Sciences.

Figures

Figure 1
Figure 1
Comparison of European Committee on Antimicrobial Susceptibility testing wild-type azole minimum inhibitory concentrations distribution of A. flavus and A. fumigatus.
See this image and copyright information in PMC

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