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. 2022 Apr 15:10:835092.
doi: 10.3389/fpubh.2022.835092. eCollection 2022.

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

Yuerong Wang  1 , Luwen Zhang  1 , Longrong Zhou  1 , Min Zhang  1 , Yuanhong Xu  1
Affiliations

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

Yuerong Wang et al. Front Public Health. .

Abstract

Background: This 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.

Methods: In 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.

Results: The 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.

Conclusions: The 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.

Keywords: Aspergillus spp.; antifungal sensitivity; azole resistance; invasive aspergillosis; risk factors.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Representative culturing macroscopic results of Aspergillus spp. (Sabouraud Dextrose agar medium). I–III: Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger. (B) Representative identification information of Aspergillus spp. by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). I–III: A. fumigatus, A. flavus, and A. niger. (C) Chest CT imaging features of patients with invasive pulmonary aspergillosis.
Figure 2
Figure 2
The species distribution of 156 Aspergillus isolates in the present study.
Figure 3
Figure 3
The department distribution of patients infected with invasive Aspergillus isolates. Res, Department of Respiratory Medicine; ICU, Intensive Care Unit; Inf, Infection Unit; Bus, Burns Unit; Urs, Department of Urology; Rhe, Department of Rheumatology and Immunology; Neu, Department of Neurology; Sur, Department of Surgery including organ transplantation, hepatobiliary and pancreatic surgery, gastrointestinal surgery, and joint surgery; Hem, Department of Hematology; Eme, Emergency Room; End, Department of Endocrinology; Nep, Department of Nephrology; Reh, Department of Rehabilitation; Ped, Department of Pediatrics; Ort, Department of Orthopedics; Oto, Department of Otolaryngology; Car, Department of Cardiology; Dis, Department of Gastroenterology; Der, Department of Dermatological Venereology; Ces, Department of Chest Surgery.
Figure 4
Figure 4
The minimum inhibitory or effective concentration distribution of amphotericin B (AMB), flucytosine (FC), micafungin (MIF), caspofungin (CAS), isavuconazole (ISA), voriconazole (VRC), posaconazole (POS), and itraconazole (ITR) for the indicated Aspergillus spp.
Figure 5
Figure 5
Correlation analyses with scatter plots to compare multiple antifungal minimum inhibitory concentrations (MICs) as indicated. The significant correlation of ISA and VRC (R2 = 0.81) was shown for Aspergillus spp. A strong correlation suggests considerable cross-resistance. (A) ISA vs VRC; (B) ISA vs POS; (C) ISA vs ITR; (D) VRC vs POS; (E) VRC vs ITR; and (F) POS vs ITR.
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