title: Increasing trend of fluconazole-non-susceptible Cryptococcus neoformans in patients with invasive cryptococcosis: a 12-year longitudinal study.
abstract: BACKGROUND
  This study aimed to investigate the rate of fluconazole-non-susceptible Cryptococcus neoformans in Southern Taiwan for the period 2001-2012 and analyze the risk factors for acquiring it among patients with invasive cryptococcosis.
  
  
  METHODS
  All enrolled strains were isolated from blood or cerebrospinal fluid samples of the included patients. If a patient had multiple positive results for C. neoformans, only the first instance was enrolled. Susceptibility testing was performed using the Clinical and Laboratory Standards Institutes M27-A3 broth micro-dilution method. The MIC interpretative criteria for susceptibility to fluconazole were ≤ 8 μg/ml. A total of 89 patients were included. Patients (n = 59) infected by fluconazole-susceptible strains were compared with those (n = 30) infected by non-susceptible strains. The patients' demographic and clinical characteristics were analyzed.
  
  
  RESULTS
  The rate of fluconazole-non-susceptible C. neoformans in the study period significantly increased over time (p < 0.001). The C. neoformans isolated in 2011-2012 (odds ratio: 10.68; 95 % confidence interval: 2.87-39.74; p < 0.001) was an independent predictive factor for the acquisition of fluconazole-non-susceptible C. neoformans.
  
  
  CONCLUSIONS
  The rate of fluconazole-non-susceptible C. neoformans has significantly increased recently. Continuous and large-scale anti-fungal susceptibility tests for C. neoformans are warranted to confirm this trend.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. sonice83@yahoo.com.tw.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. robins.chang@msa.hinet.net.
authors.forename: Tzu-Yao
authors.initials: TY
authors.lastname: Chang
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. jwliu@adm.cgmh.org.tw.|Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung City, 833, Taiwan. jwliu@adm.cgmh.org.tw.
authors.forename: Jien-Wei
authors.initials: JW
authors.lastname: Liu
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. basophil2000@yahoo.com.tw.
authors.forename: Fang-Ju
authors.initials: FJ
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. jessica0307@adm.cgmh.org.tw.
authors.forename: Chun-Chih
authors.initials: CC
authors.lastname: Chien
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. lee900@adm.cgmh.org.tw.|Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung City, 833, Taiwan. lee900@adm.cgmh.org.tw.
authors.forename: Chen-Hsiang
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung City, 833, Taiwan. chlu99@ms44.url.com.tw.|Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung City, 833, Taiwan. chlu99@ms44.url.com.tw.|Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan. chlu99@ms44.url.com.tw.
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002555:Cerebrospinal Fluid / Q000382:microbiology; D003453:Cryptococcosis / Q000188:drug therapy / Q000382:microbiology*; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000302:isolation & purification; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D005260:Female; D015725:Fluconazole / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012307:Risk Factors; D012703:Serotyping
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole