Chen Yi-Chun, Kuo Shu-Fang, Lin Shang-Yi, Lin Yin-Shiou, Lee Chen-Hsiang
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.
Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.
J Fungi (Basel). 2022 Mar 11;8(3):287. doi: 10.3390/jof8030287.
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.
隐球菌性脑膜脑炎（CM）是一种可治疗的疾病，但会导致较高的发病率和死亡率。我们在2013年至2020年期间收集了台湾南部115株非重复的隐球菌临床分离株，以进行抗真菌药敏试验。对96株来自CM患者（n = 47）或隐球菌血症患者（n = 49）的菌株进行了多位点序列分型。此外，比较了2013年至2020年期间（n = 47）和2000年至2010年期间（n = 46）CM患者的流行病学和临床特征。在2013年至2020年期间，仅1株新型隐球菌分离株（0.9%）的氟康唑最低抑菌浓度>8 μg/mL。两性霉素B（AMB）、氟胞嘧啶（5FC）和伏立康唑对所有新型隐球菌/格特隐球菌分离株均具有高度活性。最常见的序列类型是ST5。在这47例CM患者中，脑脊液隐球菌抗原（CSF CrAg）滴度>1024是死亡的显著预测因素（比值比，48.33；95%置信区间，5.17−452.06）。2013年至2020年期间所有患者均采用AMB和5FC的标准诱导治疗方案，但在2000年至2010年期间仅2.2%的患者使用。尽管2000年至2010年期间患者明显更年轻且CSF CrAg>1024的患者较少，但住院CM死亡率从2000年至2010年期间的39.1%降至2013年至2020年期间的25.5%。该研究为台湾南部隐球菌菌株的遗传流行病学和抗真菌药敏性提供了见解。推荐的抗真菌药物AMB、5FC和氟康唑（FCZ）对大多数隐球菌菌株仍具有活性。为改善CM患者的预后，CM患者的早期诊断和遵循临床实践指南再怎么强调也不为过。
