title: Invasive fungal infections following liver transplantation: incidence, risk factors, survival, and impact of fluconazole-resistant Candida parapsilosis (2003-2007).
abstract: Invasive fungal infections (IFIs) are associated with a high mortality rate for liver transplantation (LT) recipients. To study the incidence of and risk factors for IFIs in LT recipients and the associated mortality rates, we retrospectively reviewed the records of first-time deceased donor LT recipients (January 2003 to December 2007). The incidence of IFIs was 12%. Non-albicans Candida species accounted for 55% of IFIs; 50% of these IFIs were Candida parapsilosis. Only 43% of Candida isolates were fluconazole-susceptible (minimum inhibitory concentration ≤ 8 μ/mL). All C. parapsilosis isolates were fluconazole-resistant, and this coincided with a surge of these isolates during a peak period of LT. Factors associated with IFIs included a creatinine level > 2 mg/mL [hazard ratio (OR) = 2.4, 95% confidence interval (CI) = 1.2-5.0, P = 0.01], a Model for End-Stage Liver Disease score > 25 (OR = 2.4, 95% CI = 1.2-4.9, P = 0.02), pretransplant fungal colonization (OR = 7.0, 95% CI = 3.2-15.3, P < 0.001), and a daily prophylactic fluconazole dosage < 200 mg (OR = 2.8, 95% CI = 1.1-7.4, P = 0.03). According to a multivariate analysis, only pretransplant fungal colonization was associated with IFIs (OR = 7.8, 95% CI = 3.9-16.2, P < 0.001). The 1-year patient survival rates with and without IFIs were 41% and 80%, respectively, and the survival rates with C. parapsilosis, other non-albicans Candida, and Candida albicans IFIs were 28%, 50%, and 75%, respectively. In conclusion, IFIs after LT (especially non-albicans Candida species and fluconazole-resistant C. parapsilosis) were associated with reduced survival. The risk factors highlight the importance of pretransplant risk assessments. The identification of pretransplant fungal colonization may allow for risk modifications before or at the time of LT. Additionally, the number of LT procedures and prophylactic strategies may affect institutional outbreaks of resistant Candida strains.
authors.affiliation: Department of Internal Medicine, Blessing Physician Services, Quincy, IL, USA.
authors.forename: Anupama
authors.initials: A
authors.lastname: Raghuram
authors.forename: Alejandro
authors.initials: A
authors.lastname: Restrepo
authors.forename: Saman
authors.initials: S
authors.lastname: Safadjou
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cooley
authors.forename: Mark
authors.initials: M
authors.lastname: Orloff
authors.forename: Dwight
authors.initials: D
authors.lastname: Hardy
authors.forename: Sam
authors.initials: S
authors.lastname: Butler
authors.forename: Christine E
authors.initials: CE
authors.lastname: Koval
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use*; D002175:Candida / Q000145:classification / Q000187:drug effects / Q000302:isolation & purification; D016009:Chi-Square Distribution; D025141:Drug Resistance, Fungal; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation / Q000009:adverse effects* / Q000401:mortality; D016015:Logistic Models; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D015999:Multivariate Analysis; D009181:Mycoses / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology* / Q000401:mortality; D016017:Odds Ratio; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole