A 20-Year Antifungal Susceptibility Surveillance (From 1999 to 2019) for Aspergillus spp. and Proposed Epidemiological Cutoff Values for Aspergillus fumigatus and Aspergillus flavus: A Study in a Tertiary Hospital in China

Abstract

The emergence of resistant Aspergillus spp. is increasing worldwide. Long-term susceptibility surveillance for clinically isolated Aspergillus spp. strains is warranted for understanding the dynamic change in susceptibility and monitoring the emergence of resistance. Additionally, neither clinical breakpoints (CBPs) nor epidemiological cutoff values (ECVs) for Aspergillus spp. in China have been established. In this study, we performed a 20-year antifungal susceptibility surveillance for 706 isolates of Aspergillus spp. in a clinical laboratory at Peking University First Hospital from 1999 to 2019; and in vitro antifungal susceptibility to triazoles, caspofungin, and amphotericin B was determined by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. It was observed that Aspergillus fumigatus was the most common species, followed by Aspergillus flavus and Aspergillus terreus. Forty isolates (5.7%), including A. fumigatus, A. flavus, A. terreus, Aspergillus niger, and Aspergillus nidulans, were classified as non-wild type (non-WT). Importantly, multidrug resistance was observed among A. flavus, A. terreus, and A. niger isolates. Cyp51A mutations were characterized for 19 non-WT A. fumigatus isolates, and TR34/L98H/S297T/F495I was the most prevalent mutation during the 20-year surveillance period. The overall resistance trend of A. fumigatus increased over 20 years in China. Furthermore, based on ECV establishment principles, proposed ECVs for A. fumigatus and A. flavus were established using gathered minimum inhibitory concentration (MIC)/minimum effective concentration (MEC) data. Consequently, all the proposed ECVs were identical to the CLSI ECVs, with the exception of itraconazole against A. flavus, resulting in a decrease in the non-WT rate from 6.0 to 0.6%.

A Satellite dsRNA Attenuates the Induction of Helper Virus-Mediated Symptoms in Aspergillus flavus

“…Unfortunately, only three categories of antifungal drugs are used to treat IA, such as polyenes (amphotericin B), triazoles (itraconazole, voriconazole and posaconazole), and echinocandins (caspofungin and micafungin) ( Perlin et al, 2017 ). Moreover, antifungal antibiotics have some toxicity to humans, and control of A. flavus becomes more difficult with antibiotic resistance to current antifungal drugs ( Paul et al, 2015 ; Espinel-Ingroff et al, 2021 ; Yang et al, 2021 ). Mycoviruses selectively infect fungi, and have the potential for treatment of pathogenic fungal infections ( Van De Sande et al, 2010 ; Bhatti et al, 2011 ; Özkan and Coutts, 2015 ).…”

Epidemiology and Susceptibility Profile of Aspergillus Species: An Experience from Tertiary Care Hospital

“…Aspergillus fumigatus is the most often isolated Aspergillus species in China [18], followed by Aspergillus flavus and Aspergillus niger. Aspergillus species other than A. fumigatus have also been increasingly responsible for IA in recent years in China.…”

COVID-19-Associated Fungal Infections: An Urgent Need for Alternative Therapeutic Approach?

“…Microbial resistance is common in certain fungal species and involves both intrinsic resistance (strains are inherently less susceptible to a given antifungal agent), and secondary resistance (acquired resistance in an otherwise susceptible strain following drug exposure). The most notable species emerging worldwide and regarded as major concern for public health are triazole-resistant Aspergillus fumigatus ( Verweij et al, 2016 ; Romero et al, 2019 ; Yang et al, 2021 ), C. tropicalis, C. parapsilosis ( Pfaller et al, 2019 ), multidrug-resistant (MDR) Candida auris ( Chowdhary et al, 2018 ; Chaabane et al, 2019 ; Chow et al, 2020 ) and MDR C. glabrata showing increasing prevalence globally ( Haeley and Perlin, 2018 ). The narrow spectrum activity and cross-resistance due to similar mechanisms of action across drugs has triggered the search for safer alternatives with reduced toxicity, improved pharmacodynamics and pharmacokinetics, and increased specificity ( Parente-Rocha et al, 2017 ; Gintjee et al, 2020 ; Duncan et al, 2021 ).…”