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

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.

Keywords: amphotericin B; azole; cryptococcemia; cryptococcosis; flucytosine; molecular typing; mortality.

Figure 1

Population structure of clinical isolates of C. neoformans in Taiwan (Multilocus sequence typing). Minimum-spanning tree of the 8 detected sequence types and their relative distribution of 90 clinical isolates. The circle sizes are proportional to the numbers of isolates. The numbers near the circles represent the sequence types.

Figure 2

Evolution of CSF CrAg titers in 34 patients who had more than 1 determination of CrAg titers according to the day of diagnosis. CSF CrAg titer > 1024 is presented as 2048. CSF, cerebrospinal fluid; CrAg, cryptococcal antigen.