Multiple Fungicide-Driven Alterations in Azole-Resistant<i>Aspergillus fumigatus</i>, Colombia, 2015

Pape, Patrice Le; Lavergne, Rose‐Anne; Morio, Florent; Álvarez-Moreno, Carlos

doi:10.3201/eid2201.150978

Cited by 48 publications

(42 citation statements)

References 7 publications

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“…Resistance is also reported outside Europe in Turkey, Iran, Kuwait, Japan, China, Taiwan, Pakistan, India, Tanzania and Australia [46 -53,57], so far mainly associated with TR 34 /L98H but increasingly also TR 46 /Y121F/T289A. In the United States and Colombia, azole resistance owing to environmental mutations was reported recently [54,58]. Extensive asexual sporulation, the ability to survive in very different environmental conditions, and the hydrophobicity of spores, faciliating airborne dispersibility, probably enable the global spread of resistance from its centres of origin [31,79].…”

Section: The Environmental Route Of Disseminationmentioning

confidence: 99%

Clinical implications of globally emerging azole resistance in Aspergillus fumigatus

Meis

Chowdhary

Rhodes

et al. 2016

Phil. Trans. R. Soc. B

250

240

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One contribution of 18 to a discussion meeting issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'. Aspergillus fungi are the cause of an array of diseases affecting humans, animals and plants. The triazole antifungal agents itraconazole, voriconazole, isavuconazole and posaconazole are treatment options against diseases caused by Aspergillus. However, resistance to azoles has recently emerged as a new therapeutic challenge in six continents. Although de novo azole resistance occurs occasionally in patients during azole therapy, the main burden is the aquisition of resistance through the environment. In this setting, the evolution of resistance is attributed to the widespread use of azole-based fungicides. Although ubiquitously distributed, A. fumigatus is not a phytopathogen. However, agricultural fungicides deployed against plant pathogenic moulds such as Fusarium, Mycospaerella and A. flavus also show activity against A. fumigatus in the environment and exposure of non-target fungi is inevitable. Further, similarity in molecule structure between azole fungicides and antifungal drugs results in cross-resistance of A. fumigatus to medical azoles. Clinical studies have shown that twothirds of patients with azole-resistant infections had no previous history of azole therapy and high mortality rates between 50% and 100% are reported in azole-resistant invasive aspergillosis. The resistance phenotype is associated with key mutations in the cyp51A gene, including TR 34 /L98H, TR 53 and TR 46 /Y121F/T289A resistance mechanisms. Early detection of resistance is of paramount importance and if demonstrated, either with susceptibility testing or through molecular analysis, azole monotherapy should be avoided. Liposomal amphotericin B or a combination of voriconazole and an echinocandin are recomended for azole-resistant aspergillosis.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'.

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Section: The Environmental Route Of Disseminationmentioning

confidence: 99%

Clinical implications of globally emerging azole resistance in Aspergillus fumigatus

Meis

Chowdhary

Rhodes

et al. 2016

Phil. Trans. R. Soc. B

250

240

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“…The first route, identified in the late 1990s, results from in vivo drug selection through long‐term azole exposure, as illustrated in patients with chronic pulmonary aspergillosis . The second route, relies on de novo acquisition of azole‐resistant A. fumigatus strains (usually displaying the TR 34 /L98H mutations in the CYP51A gene), arising in our environment as a consequence of intensive azole fungicides use in agricultural and flower fields practices . Since then, several studies have been conducted to evaluate the burden of azole resistance among patients with invasive aspergillosis, chronic pulmonary aspergillosis or patients with cystic fibrosis .…”

Section: Introductionmentioning

confidence: 99%

PCR‐based detection of Aspergillus fumigatus and absence of azole resistance due to TR₃₄/L98H in a french multicenter cohort of 137 patients with fungal rhinosinusitis

Morio

Dannaoui

Chouaki

et al. 2017

Mycoses

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SummaryFungal rhinosinusitis (FRS) has a worldwide distribution, comprises distinct clinical entities but is mostly due to Aspergillus among which Aspergillus fumigatus plays a major role in European countries. Although, there is accumulating evidence for the emer- when using culture as the reference method. Importantly, neither TR 34 nor L98H alterations were evidenced. K E Y W O R D SAspergillus fumigatus, azole resistance, fungal rhinosinusitis, PCR-based detection, TR 34 /L98H

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“…Given this possible association between the use of DMI in agriculture and the emergence of azole-resistant A. fumigatus 341213 and the fact that Colombia is a country with a high flower production (second producer worldwide), we recently evaluated the presence of environmental resistance to azoles of medical importance in A. fumigatus isolated from flower fields and described the first environmental azole-resistant A. fumigatus strains in South America14. To gain further insights into this potential public health issue, we decided to conduct a complementary study by extending the sampling and to explore the genetic relationship between strains found in flower fields, ornamental plant beds and urban public gardens.…”

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confidence: 99%

Azole-resistant Aspergillus fumigatus harboring TR34/L98H, TR46/Y121F/T289A and TR53 mutations related to flower fields in Colombia

Álvarez-Moreno

Lavergne

Hagen

et al. 2017

Sci Rep

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100

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Resistance to triazoles in Aspergillus fumigatus has been reported in azole-naive patients in Europe, Asia, Australia and North America. This resistance has been linked to fungicide-driven mutations in the cyp51A gene and its promoter region. We investigated the presence of environmental azole-resistant A. fumigatus strains related to the use of azole fungicides in Colombia. Soil samples were collected from flower beds, flower fields and public gardens from the outskirts, suburbs and city centre of Bogotá. Out of the 86 soil samples taken, 17 (19.8%) grew A. fumigatus of whom eight (9.3%) contained 40 strains able to grow on azole-containing itraconazole and/or voriconazole supplemented media. All but one triazole-resistant strains were isolated from soil samples collected from flower fields and flower beds (39/40). Importantly, the majority had the TR46/Y121F/T289A, TR34/L98H, and TR53 molecular resistance mechanisms and one azole resistant strain had a wild-type cyp51A gene. Soil samples from flower fields and beds contained 4 azole fungicides (penconazole, difenoconazole, tetraconazole and tebuconazole) above the limit of detection. Our findings underline the need for extensive investigations to determine azole-resistant A. fumigatus prevalence in both clinical and environmental samples in other regions of Latin America.

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Multiple Fungicide-Driven Alterations in Azole-ResistantAspergillus fumigatus, Colombia, 2015

Cited by 48 publications

References 7 publications

Clinical implications of globally emerging azole resistance in Aspergillus fumigatus

Clinical implications of globally emerging azole resistance in Aspergillus fumigatus

PCR‐based detection of Aspergillus fumigatus and absence of azole resistance due to TR₃₄/L98H in a french multicenter cohort of 137 patients with fungal rhinosinusitis

Azole-resistant Aspergillus fumigatus harboring TR34/L98H, TR46/Y121F/T289A and TR53 mutations related to flower fields in Colombia

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Multiple Fungicide-Driven Alterations in Azole-ResistantAspergillus fumigatus, Colombia, 2015

Cited by 48 publications

References 7 publications

Clinical implications of globally emerging azole resistance in Aspergillus fumigatus

Clinical implications of globally emerging azole resistance in Aspergillus fumigatus

PCR‐based detection of Aspergillus fumigatus and absence of azole resistance due to TR34/L98H in a french multicenter cohort of 137 patients with fungal rhinosinusitis

Azole-resistant Aspergillus fumigatus harboring TR34/L98H, TR46/Y121F/T289A and TR53 mutations related to flower fields in Colombia

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PCR‐based detection of Aspergillus fumigatus and absence of azole resistance due to TR₃₄/L98H in a french multicenter cohort of 137 patients with fungal rhinosinusitis