RESUMO
The best treatment for patients with invasive aspergillosis caused by cryptic Aspergillus species remains uncertain, mainly due to the limited clinical data that have been published so far. In face of this limitation, patients should be treated with standard first-line therapy for invasive aspergillosis, with therapy being modified according to in vitro susceptibility testing. In this review, we summarize the importance of cryptic Aspergillus species in modern medicine, including their prevalence, methods for detection and response to antifungal drugs.
Assuntos
Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergillus/classificação , Aspergilose/diagnóstico , Aspergillus/genética , Aspergillus/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Resultado do TratamentoRESUMO
Azoles are the mainstay of oral therapy for aspergillosis. Azole resistance in Aspergillus has been reported infrequently. The first resistant isolate was detected in 1999 in Manchester, UK. In a clinical collection of 519 A. fumigatus isolates, the frequency of itraconazole resistance was 5%, a significant increase since 2004 (p<0.001). Of the 34 itraconazole-resistant isolates we studied, 65% (22) were cross-resistant to voriconazole and 74% (25) were cross-resistant to posaconazole. Thirteen of 14 evaluable patients in our study had prior azole exposure; 8 infections failed therapy (progressed), and 5 failed to improve (remained stable). Eighteen amino acid alterations were found in the target enzyme, Cyp51A, 4 of which were novel. A population genetic analysis of microsatellites showed the existence of resistant mutants that evolved from originally susceptible strains, different cyp51A mutations in the same strain, and microalterations in microsatellite repeat number. Azole resistance in A. fumigatus is an emerging problem and may develop during azole therapy.