Epidemiology, Drug Susceptibility, and Clinical Risk Factors in Patients With Invasive Aspergillosis

Abstract

BackgroundThis study aimed to investigate the Aspergillus species distribution, antifungal sensitivities, clinical characteristics, and risk factors of patients with invasive aspergillosis (IA) in a tertiary teaching hospital in Anhui Province.MethodsIn the present study, 156 Aspergillus isolates were collected from patients admitted to a 2,800-bed comprehensive hospital between January 2019 and April 2021. The epidemiology of Aspergillus species was well-examined, and its antifungal susceptibility was specifically measured by the microbroth dilution method. The risk factors of patients with IA were documented and analyzed intensively. In addition, gene sequencing was employed to determine gene mutations of cytochrome P450 14-α sterol demethylase-Aspergillus (cyp51A) associated with azole resistance among Aspergillus fumigatus.ResultsThe Aspergillus species distribution was dominated by A. fumigatus (56.41%), Aspergillus flavus (20.51%), and Aspergillus niger (15.38%) locally. In particular, all Aspergillus species showed very low minimum inhibitory concentrations (MICs, ≤ 0.5 μg/ml) for azoles and echinocandins, slightly high MICs (1.66–2.91 μg/ml) for amphotericin B, and exceptionally high MICs (>64 μg/ml) for flucytosine. Azole-resistant rate of Aspergillus species in this local region reached up to 5.79%. Correlation analyses of multiple antifungals indicate a significant MIC relevance between isavuconazole and voriconazole (Pearson correlation coefficient was 0.81, P < 0.0001). The clinical risk factors for patients with IA were found primarily to be pulmonary diseases (P = 0.007) and patients' age (P < 0.001). Notably, three mutant loci (TR46/Y121F/T289A) of the cyp51A gene were identified in azole-resistant A. fumigatus.ConclusionsThe Aspergillus species emerged increasingly, of which A. fumigatus and A. flavus remained the main pathogens for invasive Aspergillus infections in the local region. The vast majority of Aspergillus species exhibited good susceptibility to all the antifungals, except flucytosine. The local occurrence of azole-resistant Aspergillus species grew gradually and needed monitoring in time. Pulmonary diseases and age were likely considered as highly associated risk factors for IA. To our knowledge, the clinically isolated azole-resistant A. fumigatus with TR46/Y121F/T289A mutations identified here were rarely reported in the area of China.

Antifungal Susceptibility and Genotypic Analysis of cyp51A Mutations in Aspergillus fumigatus Isolates in Malaysia

“…Specifically, this comprised of 3.3% (2/60) resistance solely to amphotericin B, 1.7% to voriconazole, and 1.7% exhibited resistance to both itraconazole and amphotericin B. This azole-resistance rate is consistent with previous studies in Asia, including China, [35][36][37] Japan, 38 Pakistan, 39 Korea, 40 where the azole-resistance was less than 10%. However, azole resistance rates were significantly higher in other regions.…”

A nomogram model in invasive pulmonary aspergillosis diagnosis based on a retrospective study

“…Due to the fact that previous literature on the identification of IPA has established evaluation criteria specific to different populations, such as individuals with blood disorders or ICU patients, who are considered high-risk groups, there is currently no universal standard applicable to all populations.A retrospective study in hospitalized patients with positive Aspergillus culture from lower airway samples found that 66.6% of those fulfilled putative invasive pulmonary aspergillosis [7] .Our research referenced its evaluation criteria and found that the proportion of IPA was 52.8%. In this study, the most common underlying systemic condition was tracheal and bronchial diseases, mainly including pulmonary/bronchial inflammation and COPD, as previous reports [15] . Thus, tracheal and bronchial diseases were identified as an important risk factor for IPA.…”

Epidemiology and Azole Resistance of Clinical Isolates of Aspergillus fumigatus from a Large Tertiary Hospital in Ningxia, China

“…The prevalence of azole-resistant Aspergillus species varies geographically. Our study found that 2 out of 276 samples (0.72%) were resistant to VRC and non-wild type for ITC, which is lower compared to Beijing (4.3%), 60 Shanghai (3.57–7.02%), 61 , 62 and Anhui (5.79%) 63 in China. In a separate study conducted in China, A. fumigatus isolates were collected from various regions, revealing a 4.4% frequency of azole resistance.…”