Abstract

BackgroundInvasive aspergillosis (IA) is a leading cause of morbidity and mortality in immunocompromised hosts. Triazole resistance in Aspergillus fumigatus is emerging globally. We performed antifungal susceptibility testing (AST) in Aspergillus isolates from Mexico and evaluated risk factors associated with 6 week mortality, including the MICs.MethodsAspergillus isolates from clinical samples were collected in a tertiary care center from 2014 to 2018. Species-level identification and broth microdilution following the CLSI M38 method were performed. MICs were interpreted according to epidemiological cutoff values. PCR and cyp51A gene sequencing were performed in A. fumigatus isolates with voriconazole (VRC) MIC >1 µg/mL. Data from the medical record were obtained to classify patients according to the MSG/EORTC criteria. The relationship between the MICs and 6-week mortality was described. Multivariate analysis of factors associated with six week mortality was performed.ResultsAST was performed on 85 Aspergillus isolates: 60/85 from patients with IA, 15/85 from patients with Aspergillus colonization, 2 patients with Aspergilloma, 1 with chronic otitis media and 1 with endophtalmitis. Information from 6 patients was unavailable. VRC MIC > 1 µg/mL was found in 3/38 (7.8%) A. fumigatus, from two patients with IA. Both had a TR34/L98H mutation in the cyp51A gene. Amphotericin B (AmB) MICs ≥ 2 were found in 16/49 (32%) A. fumigatus, 10/15 (66%) A. flavus and 1/14 (8%) A. niger. Forty-one patients with IA were treated: 29/41 (71%) with VRC or posaconazole, 7/41 (17%) with AmB and 5 with combination therapy. Overall, 6-week mortality was 30/49 (61.2%) among patients with IA; 2/2 (100%) when VRC MIC >1 µg/mL and 12/19 (63%) when AmB > 2 µg/mL, of which only 4 patients received initial treatment with AmB. Age older than 65 years (OR 11.8; 95% CI 1.14–123) and hepatic failure (OR 7.9; 95% CI 1.22–50.9) were independently associated with 6-week mortality in multivariate analysis.ConclusionWe found a VRC MIC >1 µg/mL prevalence of 7.8% among A. fumigatus and a high prevalence of AmB MIC ≥ 2 among clinical isolates of Aspergillus in Mexico. Elevated mortality was seen in IA among older patients with hepatic failure. Larger epidemiological studies are warranted.Disclosures All authors: No reported disclosures.

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