Epidemiological and Clinical Characteristics, Antifungal Susceptibility, and MLST-Based Genetic Analysis of Cryptococcus Isolates in Southern Taiwan in 2013-2020.

Yi-Chun Chen,Yin-Shiou Lin,Shang-Yi Lin,Chen-Hsiang Lee,Shu-Fang Kuo

doi:10.3390/jof8030287

Abstract

Cryptococcal meningoencephalitis (CM) is a treatable condition, but it leads to excessive morbidity and mortality. We collected 115 non-duplicated Cryptococcus clinical isolates during 2013–2020 in southern Taiwan to perform antifungal susceptibility testing. Multi-locus sequence typing was performed on 96 strains from patients with CM (n = 47) or cryptococcemia (n = 49). In addition, the epidemiological and clinical characteristics of patients with CM during 2013–2020 (n = 47) were compared with those during 2000–2010 (n = 46). During 2013–2020, only one C. neoformans isolate (0.9%) had a fluconazole minimum inhibitory concentration of >8 μg/mL. Amphotericin B (AMB), flucytosine (5FC), and voriconazole were highly active against all C. neoformans/C. gattii isolates. The most common sequence type was ST5. Among these 47 patients with CM, cerebrospinal fluid cryptococcal antigen (CSF CrAg) titer >1024 was a significant predictor of death (odds ratio, 48.33; 95% CI, 5.17–452.06). A standard induction therapy regimen with AMB and 5FC was used for all patients during 2013–2020, but only for 2.2% of patients in 2000–2010. The in-hospital CM mortality rate declined from 39.1% during 2000–2010 to 25.5% during 2013–2020, despite there being significantly younger patients with less CSF CrAg >1024 during 2000–2010. The study provides insight into the genetic epidemiology and antifungal susceptibility of Cryptococcus strains in southern Taiwan. The recommended antifungal drugs, AMB, 5FC, and FCZ, remained active against most of the Cryptococcus strains. Early diagnosis of patients with CM and adherence to the clinical practice guidelines cannot be overemphasized to improve the outcomes of patients with CM.

Highlights

Cryptococcosis, a potentially fatal mycosis worldwide, is caused by members of the Cryptococcus neoformans and C. gattii species complexes [1,2]
The purpose of the present study was to determine the antifungal susceptibility of clinical strains of C. neoformans and C. gattii collected in southern Taiwan to amphotericin B (AMB), 5FC, FCZ, posaconazole (PCZ), and voriconazole (VCZ) using standard methods (Clinical and Laboratory Standards Institute, CLSI M27-A3 broth microdilution) [24]
Our results demonstrated that all six C. gattii strains were uniformly WT to AMB, FCZ, 5FC, and VCZ

Summary

Introduction

Cryptococcosis, a potentially fatal mycosis worldwide, is caused by members of the Cryptococcus neoformans and C. gattii species complexes [1,2]. Efficient clinical support, and proper antifungal therapy are essential factors to reduce the mortality and adverse impacts of cryptococcosis [5]. CM often involves patients with advanced human immunodeficiency virus (HIV) disease, malignancy, and immunosuppressive conditions, such as recipients of solid-organ transplants. The antifungal treatment of CM involves sequential therapeutic phases, including induction, consolidation, and maintenance phases. A course of amphotericin B (AMB) with flucytosine (5FC) followed by fluconazole (FCZ) as consolidation and maintenance is considered as the benchmark in antifungal therapy for CM [8]. Liposomal amphotericin B (LAmB) is a preferred alternative to conventional AMB, with similar outcomes and less nephrotoxicity [9], and is recommended for primary induction in patients at risk of renal dysfunction

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