title: Epidemiology of candidemia in Qatar, the Middle East: performance of MALDI-TOF MS for the identification of Candida species, species distribution, outcome, and susceptibility pattern.
abstract: BACKGROUND
  Bloodstream infections (BSIs) due to Candida spp. constitute the predominant group of hospital-based fungal infections worldwide. A retrospective study evaluated the performance of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the identification of BSI Candida isolates. The epidemiology, risk factors, demographic features, species distribution, and clinical outcome associated with candidemia in patients admitted to a single tertiary-care hospital in Qatar, were analyzed.
  
  
  METHODS
  A single-center, retrospective analysis covering the period from January 1, 2004 to December 31, 2010 was performed. Molecular identification used sequence analysis of the D1/D2 domains of the large subunit ribosomal DNA (LSU rDNA) and the ITS1/2 regions of the rDNA. MALDI-TOF MS-based identification of all yeast isolates was performed with the ethanol/formic acid extraction protocol according to Bruker Daltonics (Bremen, Germany). The susceptibility profiles of 201 isolates to amphotericin B, itraconazole, fluconazole, voriconazole, anidulafungin, caspofungin, posaconazole, and isavuconazole were tested using CLSI standard broth microdilution method (M27-A3 and M27 S4) guidelines. Statistical analyses were performed with the statistical package SPSS 19.0.
  
  
  RESULTS
  A total of 187 patients with 201 episodes of candidemia were identified. Candida albicans was the most common species isolated (33.8 %; n = 68), whereas non-albicans Candida species represented 66.2 % (n = 133) of the episodes. The species distribution and outcome of candidemia showed a difference in the crude mortality between patients infected with C. albicans (n = 30; 45.5 %) and non-albicans Candida species. For example, C. parapsilosis candidemia was associated with the lowest mortality rate (40.6 %), and patients with other non-albicans species had the highest mortality rate (68-71.4 %). High mortality rates were observed among pediatric (<1 year of age) and elderly patients (>60 years of age). All strains showed low minimum inhibitory concentrations (MICs) (MIC90 of 0.063 μg/ml) to isavuconazole. The overall resistance to voriconazole in vitro antifungal activity was 2.5 %. C. glabrata (n = 38) had an MIC90 of 8 μg/ml for fluconazole. Most yeast isolates were susceptible to anidulafungin (>99.5 %) and 81.1 % to caspofungin. Resistance to anidulafungin was detected in 1/8 (12.5 %) isolates of C. orthopsilosis. According to new Clinical and Laboratory Standards Institute (CLSI) breakpoints, C. glabrata (n = 38) showed 100 % resistance, and 37/68 (54.4 %) C. albicans isolates were susceptible dose dependent (SDD) to caspofungin. Identification by MALDI-TOF MS was in 100 % concordance with molecular identification.
  
  
  CONCLUSIONS
  The Middle East epidemiology of candidemia has a unique species distribution pattern distinct from other parts of the globe. High mortality rates were observed among pediatric (<1 year of age) and elderly patients (>60 years of age). All strains were susceptible to isavuconazole. All isolates of C.glabrata were resistant to caspofungin based on M27 S4. MALDI-TOF MS is a highly useful method for the routine identification of yeast isolates in clinical setting to achieve successful therapeutic treatment.
authors.affiliation: Mycology Unit, Microbiology Division, Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar, stajaldeen@hmc.org.qa.
authors.forename: S J
authors.initials: SJ
authors.lastname: Taj-Aldeen
authors.forename: A
authors.initials: A
authors.lastname: Kolecka
authors.forename: R
authors.initials: R
authors.lastname: Boesten
authors.forename: A
authors.initials: A
authors.lastname: Alolaqi
authors.forename: M
authors.initials: M
authors.lastname: Almaslamani
authors.forename: P
authors.initials: P
authors.lastname: Chandra
authors.forename: J F
authors.initials: JF
authors.lastname: Meis
authors.forename: T
authors.initials: T
authors.lastname: Boekhout
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification* / Q000502:physiology; D058387:Candidemia / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000382:microbiology; D002648:Child; D002675:Child, Preschool; D021901:DNA, Intergenic / Q000235:genetics / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D025141:Drug Resistance, Fungal; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011780:Qatar / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D013045:Species Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D021901:DNA, Intergenic; D004275:DNA, Ribosomal