Triazole-Resistance in Environmental Aspergillus fumigatus in Latin American and African Countries

Abstract

Triazole-resistance has been reported increasingly in Aspergillus fumigatus. An international expert team proposed to avoid triazole monotherapy for the initial treatment of invasive aspergillosis in regions with >10% environmental-resistance, but this prevalence is largely unknown for most American and African countries. Here, we screened 584 environmental samples (soil) from urban and rural locations in Mexico, Paraguay, and Peru in Latin America and Benin and Nigeria in Africa for triazole-resistant A. fumigatus. Samples were screened using triazole-containing agars and confirmed as triazole-resistant by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth dilution reference method. Isolates were further characterized by cyp51A sequencing and short-tandem repeat typing. Fungicide presence in samples was likewise determined. Among A. fumigatus positive samples, triazole-resistance was detected in 6.9% (7/102) of samples in Mexico, 8.3% (3/36) in Paraguay, 9.8% (6/61) in Peru, 2.2% (1/46) in Nigeria, and none in Benin. Cyp51A gene mutations were present in most of the triazole-resistant isolates (88%; 15/17). The environmentally-associated mutations TR₃₄/L98H and TR₄₆/Y121F/T289A were prevalent in Mexico and Peru, and isolates harboring these mutations were closely related. For the first time, triazole-resistant A. fumigatus was found in environmental samples in Mexico, Paraguay, Peru, and Nigeria with a prevalence of 7-10% in the Latin American countries. Our findings emphasize the need to establish triazole-resistance surveillance programs in these countries.

Keywords: Africa; America; Aspergillus fumigatus; antifungal resistance; environment; epidemiology.

Figure 1

Circular phylogenetic tree depicting the relationship among triazole-resistant and susceptible Aspergillus fumigatus isolates. Genetic relationship between triazole-resistant isolates and selected susceptible Aspergillus fumigatus isolates from this study and selected publicly available triazole-resistant and susceptible worldwide isolates (short tandem repeat; Euclidian dissimilarity and Ward’s method for row agglomeration). Isolates were clustered into two clades: clade-I (red sample ID number) and clade-II (black sample ID number). Figures represent isolates country of origin. Color inside figures represent the cyp51A gene sequencing result (mutations) of triazole-resistant isolates. Abbreviations: ID = identification.