Triazole Resistance Is Still Not Emerging in Aspergillus fumigatus Isolates Causing Invasive Aspergillosis in Brazilian Patients

Negri, Clara E; Gonçalves, Sarah Santos; Sousa, Ana Cristina Peres De; Bergamasco, Maria Daniela; Martino, Marinês Dalla Valle; Queiroz‐Telles, Flávio; Aquino, Valério Rodrigues; Castro, Paulo de Tarso Oliveira e; Hagen, Ferry; Meis, Jacques F.; Colombo, Arnaldo Lopes

doi:10.1128/aac.00608-17

Cited by 8 publications

(7 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“… 21 In contrast, a multicenter international surveillance network performed by van der Linden et al 22 tested 3788 Aspergillus strains from different countries for azole resistance, among which 64 clinical strains recovered from Brazilian patients showed no resistance to ITZ. In addition, Negri et al 23 recently reported non-resistance to ITZ and PSC, and only intermediate MICs (2.0 mg/L) for few strains to VCZ in a study with 221 Brazilian clinical strains of A. fumigatus .…”

Section: Discussionmentioning

confidence: 99%

In vitro antifungal susceptibility of clinical and environmental isolates of Aspergillus fumigatus and Aspergillus flavus in Brazil

Denardi

Dalla-Lana

Jesus

et al. 2018

The Brazilian Journal of Infectious Diseases

View full text Add to dashboard Cite

The in vitro susceptibility of 105 clinical and environmental strains of Aspergillus fumigatus and Aspergillus flavus to antifungal drugs, such as amphotericin B, azoles, and echinocandins was evaluated by the broth microdilution method proposed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Following the EUCAST-proposed breakpoints, 20% and 25% of the clinical and environmental isolates of A. fumigatus, respectively, were found to be resistant to itraconazole (Minimal Inhibitory Concentration, MIC>2.0mg/L). Voriconazole showed good activity against A. fumigatus and A. flavus strains, except for one clinical strain of A. fumigatus whose MIC was 4.0mg/L. Posaconazole (≤0.25mg/L) also showed appreciable activity against both species of Aspergillus, except for six A. fumigatus strains with relatively higher MICs (0.5mg/L). The MICs for Amphotericin B ranged from 0.06 to 1.0mg/L for A. fumigatus, but were much higher (0.5-8.0mg/L) for A. flavus. Among the echinocandins, caspofungin showed a geometric mean of 0.078 and 0.113 against the clinical and environmental strains of A. flavus, respectively, but had elevated minimal effective concentrations (MECs) for seven of the A. fumigatus strains. Anidulafungin and micafungin exhibited considerable activity against both A. fumigatus and A. flavus isolates, except for one environmental isolate of A. fumigatus that showed an MEC of 1mg/L to micafungin. Our study proposes that a detailed investigation of the antifungal susceptibility of the genus Aspergillus from different regions of Brazil is necessary for establishing a response profile against the different classes of antifungal agents used in the treatment of aspergillosis.

show abstract

Section: Discussionmentioning

confidence: 99%

In vitro antifungal susceptibility of clinical and environmental isolates of Aspergillus fumigatus and Aspergillus flavus in Brazil

Denardi

Dalla-Lana

Jesus

et al. 2018

The Brazilian Journal of Infectious Diseases

View full text Add to dashboard Cite

show abstract

“…In Brazil, many researchers are studying the azole susceptibility profiles of A. fumigatus strains (12)(13)(14), and at present, there is one abstract from ISHAM 20th describing TR34/L98H mutations found in a clinical A. fumigatus isolate and a CYP51A gene point mutation resulting in an M220R mutation obtained from an isolate collected from a crop in southern Brazil (15).…”

mentioning

confidence: 99%

Aspergillus fumigatus Clinical Isolates Carrying CYP51A with TR34/L98H/S297T/F495I Substitutions Detected after Four-Year Retrospective Azole Resistance Screening in Brazil

Pontes

Beraquet

Arai

et al. 2020

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Azole antifungal resistance in Aspergillus fumigatus is a worldwide concern. As in most public hospitals in Brazil, antifungal susceptibility tests are not routinely performed for filamentous fungi at our institution. A 4-year retrospective azole antifungal resistance screening revealed two azole-resistant A. fumigatus clinical isolates carrying the CYP51A TR34 (34-bp tandem repeat)/L98H (change of L to H at position 98)/S297T/F495I resistance mechanism mutations, obtained from two unrelated patients. Broth microdilution antifungal susceptibility testing showed high MICs for itraconazole, posaconazole, and miconazole. Short tandem repeat (STR) typing analysis presented high levels of similarity between these two isolates and clinical isolates with the same mutations reported from the Netherlands, Denmark, and China, as well as environmental isolates from Taiwan. Our findings might indicate that active searching for resistant A. fumigatus is necessary. They also represent a concern considering that our hospital provides tertiary care assistance to immunocompromised patients who may be exposed to resistant environmental isolates. We also serve patients who receive prophylactic antifungal therapy or treatment for invasive fungal infections for years. In these two situations, isolates resistant to the antifungal in use may be selected within the patients themselves. We do not know the potential of this azole-resistant A. fumigatus strain to spread throughout our country. In this scenario, the impact on the epidemiology and use of antifungal drugs will significantly alter patient care, as in other parts of the world. In summary, this finding is an important contribution to alert hospital laboratories conducting routine microbiological testing to perform azole resistance surveillance and antifungal susceptibility tests of A. fumigatus isolates causing infection or colonization in patients at high risk for systemic aspergillosis.

show abstract

“…Similarly, >20% resistance was described in the Netherlands in high-risk patients [77], whereas in Spanish [78] and Dutch [79] general population, this prevalence seems to be as low as 1.8% and 4%, respectively. On the other hand, in other continents, azole resistance prevalence in high-risk patients was lower: 1.7% in India [80], 0.6-11.8% in the USA [69,81], 2.6% in Australia [82], and 1.8% in Brazil [83]. These differences in azole resistance frequencies can be skewed due to studied populations, center complexity, and even partly due to the used denominator.…”

Section: Worldwide Resistance To Triazole: Epidemiology Prevalence and Most Affected Regionsmentioning

confidence: 99%

“…from Brazil are scarce. Negri et al affirmed in 2017 that azole resistance was not emerging in Brazil, but these authors reported under that statement that they found 1.8% of the A. fumigatus isolated from invasive aspergillosis have VRC MICs above the epidemiological cut off values [83].…”

Section: Epidemiology Of Triazole Resistance In a Fumigatus In Latin American Countriesmentioning

confidence: 99%

Emergence of Triazole Resistance in Aspergillus spp. in Latin America

Macedo

Leonardelli

Gamarra

et al. 2021

Curr Fungal Infect Rep

View full text Add to dashboard Cite

Purpose of Review Azole resistance in Aspergillus spp. is becoming a public health problem worldwide. However, data about this subject is lacking in Latin American countries. This review focuses in the epidemiology and molecular mechanisms of azole resistance in Aspergillus spp. emphasizing in Latin America. Data on Aspergillus fumigatus stands out because it is the most prevalent Aspergillus spp. pathogen. Recent Findings Azole resistance in Aspergillus spp. emergence was linked with intensive use of these antifungals both in the clinical setting and in the environment (as pesticides). Reports on azole-resistant A. fumigatus strains are being constantly published in different countries. Molecular mechanisms of resistance mainly involve substitution in the azole target (CYP51A) and/or overexpression of this gene. However, several other non-CYP51A-related mechanisms were described. Moreover, intrinsically resistant cryptic Aspergillus species are starting to be reported as human pathogens. Summary After a comprehensive literature review, it is clear that azole resistance in Aspergillus spp. is emerging in Latin America and perhaps it is underestimated. All the main molecular mechanisms of azole resistance were described in patients and/or environmental samples. Moreover, one of the molecular mechanisms was described only in South America. Cryptic intrinsic azole-resistant species are also described.

show abstract

Triazole Resistance Is Still Not Emerging in Aspergillus fumigatus Isolates Causing Invasive Aspergillosis in Brazilian Patients

Cited by 8 publications

References 28 publications

In vitro antifungal susceptibility of clinical and environmental isolates of Aspergillus fumigatus and Aspergillus flavus in Brazil

In vitro antifungal susceptibility of clinical and environmental isolates of Aspergillus fumigatus and Aspergillus flavus in Brazil

Aspergillus fumigatus Clinical Isolates Carrying CYP51A with TR34/L98H/S297T/F495I Substitutions Detected after Four-Year Retrospective Azole Resistance Screening in Brazil

Emergence of Triazole Resistance in Aspergillus spp. in Latin America

Contact Info

Product

Resources

About