1. Risk Factors for Candida dubliniensis Bloodstream Infections Katherine Veltman, B.S., Peggy L. Carver, Pharm.D, FCCP The University of Michigan Health System, Institute for Clinical and Health Research, and College of Pharmacy Candida dubliniensis appears to be a newly emerging pathogen in Candida bloodstream infections (BSIs) that had previously been associated primarily with oral candidiasis in HIV-infected patients. Previous small case series (1-4 patients) have shown that the characteristics of these patients are varied but may include a history of GI or liver disease, immune system dysfunction and the use of certain medications. We reviewed clinical data from the charts of 19 patients with C. dubliniensis bloodstream infections and compared them to the characteristics of 87 control patients with either C. glabrata or C. albicans BSIs. Chi square analysis (α = 0.05) demonstrated that C. dubliniensis BSIs are significantly positively associated with age less than 55 years, liver disease, and rapid mortality within 7 days of the initial infection, as well as being acquired in-hospital vs in the community. Significant negative associations were found with corticosteroid use within 30 days prior to infection and use of residence facilities, home health care services, and outpatient wound care, infusion, and hemodialysis services. Prevalence of Risk Factors in C. dubliniensis Patients as Compared to C. albicans and C. glabrata Patients. + Includes facility residence, home health care services, and outpatient wound care, hemodialysis and infusion Prevalence of Risk Factors in C. dubliniensis Patients as Compared to C. albicans and C. glabrata BSIs Combined Prevalence of Risk Factors in C. dubliniensis Patients as Compared to C. glabrata BSIs Prevalence of Risk Factors in C. dubliniensis Patients as Compared to C. albicans BSIs *Significant result (p < 0.05) + Includes facility residence, home health care services, and outpatient wound care, hemodialysis and infusion *Significant result (p < 0.05) + Includes facility residence, home health care services, and outpatient wound care, hemodialysis and infusion * Significant result (p < 0.05) + Includes facility residence, home health care services, and outpatient wound care, hemodialysis and infusion Comparative incidence of risk factors in C. dubliniensis, C. albicans and C. glabrata BSIs *Refers to facility residence me health care, and outpatient wound care, hemodialysis and infusion Until recently, C. dubliniensis has been observed primarily as a cause of oral candidiasis, especially in HIV+ and immunocompromised patients. Although originally considered to be nonpathogenic, C. dubliniensis has emerged as an uncommon but problematic pathogen in Candida bloodstream infections (BSIs), with a mortality rate of 29%. 1 Previous reports suggested that C. dubliniensis was uncommonly seen as a BSI pathogen, with a usual prevalence of ≤ 2% of total Candida BSIs. The incidence of C. dubliniensis may be more common than previously recognized, since many health system microbiology laboratories use methods of Candida species identification that can do not accurately distinguish between C. albicans, the most common Candida species, and C. dubliniensis At the University of Michigan Health Systems (UMHS), 20 BSIs caused by C. dubliniensis have been observed in the past 11 years, with the rate of infection increasing yearly:10 episodes were observed from 2008-2010. The reasons for this increase in pathogenicity are currently unknown, although developments in identification have likely been of importance. To determine risk factors for C. dubliniensis infection so that patients can have improved speed of diagnosis and proper treatment, and allow modification of risk factors to potentially prevent infection. Hypothesis: Patients with C. dubliniensis BSIs are more likely to have certain risk factors, such as gastrointestinal tract (GIT) disease, immune system dysfunction, diabetes or liver disease, as compared to patients who develop BSIs caused by C. albicans or C. glabrata. Specific aim: To evaluate risk factors for the development of Candida BSIs caused by C. dubliniensis with those of C. albicans or C. glabrata. STUDY DESIGN Single center, retrospective, observational chart review, IRB approved Study period: 1999 to present C. dubliniensis patients: N=19 Controls: C. albicans N=50, C. glabrata N=37 INCLUSION CRITERIA All adult and pediatric blood cultures positive for C. dubliniensis during the study period; selected adult and pediatric blood cultures positive for C. albicans or C. glabrata All C. albicans cultures were identified by PNA FISH ®, which distinguishes between C. albicans and C. dubliniensis EXCLUSION CRITERIA Unclear fungal diagnosis Non-C. albicans, glabrata or dubliniensis candidemia Repeat positive blood cultures DATA COLLECTION Patient demographics, vital labs, previous and concurrent disease states, concurrent medications, dates/times of blood cultures, previous antifungals administered, C. dubliniensis treatment medications, ophthalmic examination, outcomes STATISTICAL ANALYSIS Data were analyzed using SPSS v. 19 Statistical significance was primarily analyzed via the chi square, with an α = 0.05 Our data suggests that C. dubliniensis is primarily an in-hospital infection, observed in seriously ill patients, as supported by the lack of association with outpatient health services known to transmit infection and the low number of patients entering the hospital with infection, as well as the very high mortality rate (~50%) within one week. Although 60% and 54% of patients with C. albicans and C. glabrata, respectively, received an ophthalmological exam to rule out ocular candidiasis, only 26% of patients with C. dubliniensis received an exam. Physicians may not be aware of the potential for Candida BSIs to cause ocular fungemia, or the relatively high early (<7 days after + blood culture) mortality rate of C. dubliniensis. Statistically significant positive risk factors for C. dubliniensis bloodstream infection include in-hospital stay, age less than 55, and liver disease. Negative risk factors include corticosteroid use within 30 days and facility residence, home health care, and outpatient wound care, hemodialysis and infusion. Patients were significantly less likely to receive an ophthalmic exam. Mortality was significantly more likely within 7 days of the positive culture. Identifying risk factors for the acquisition of C. dubliniensis BSIs may help prevent or mitigate infection or mortality with this pathogen. Although several published small case reports and case studies have provided characteristics of individual patients with infections caused by C. dubliniensis, risk factors related to the development of C. dubliniensis BSIs have not been examined. Identifying risk factors for the acquisition of C. dubliniensis BSIs may help prevent or mitigate infection or mortality with this pathogen. REFERENCES 1.Coleman, DC. AIDS. 11:557. 2.Khan Z. PLoS One. 2012;7(3):e32952. Epub 2012 Mar 2. 3. Gilfillan, G. D. 1998 Microbiology. 144:829. 4. Jabra-Rizk. 1999. J. Clin. Microbiol. 37:321. 5. O'Connor, L. 2010. Eukaryotic Cell. 9:1383. 6. Peltroche-Llacsahuanga, H. 2000. J Clin Mic 38:3696. 7. Polacheck, I. 2000. J Clin Mic 38:170. Risk factorC. albicansC. glabrata Both C. albicans and C. glabrata 0 or 1 days at risk Age over 55 Liver disease------ Ophthalmic exam Corticosteroid use at ≤ 30 days to positive culture ----- Neutropenia ----- Facility Services + Mortality at 7 days Summary of Risk factors for C. dubliniensis