Candidaemia in Critically Ill Patients Dr Bunny Saberwal, Mrs Rakhee Patel, Dr Seng Zhi Quan and Dr A. Gonzalez ICE 2

Background Invasive candida infections – insidious course with non- specific signs and symptoms Candidaemia is frequent cause of invasive fungal Bloodstream Infections (BSI) in hospitalised patients High candidaemia attributable mortality Early recognition can aid efforts to ensure appropriate empirical therapy is initiated → improve clinical outcome Emergence of non-albicans candida species influences choice of empirical therapy Increased mortality with delayed treatment The management of fungal infections, George H Karem MD Louisiana State University School of Medicine in New Orleans

Aim To provide a picture of local epidemiology To assess whether antifungal therapy is administered in a timely fashion Appropriate duration of therapy To evaluate risk factors, outcome and the associated costs

Standards as per IDSA guidelines Antifungal treatment within 24hrs of positive cultures Fundoscopic Examination on ALL patients with proven Candida BSI Confirmatory negative cultures IDSA Guidelines: Clinical Practice Guidelines for the management of Candidiasis: 2009 Update by the Infectious Disease Society of America, Peter G Pappas et al CID 2009:48

Methods Retrospective analysis Over period 1 st January 2005 – 31 st December 2010 Medical notes and electronic records from microbiology blood culture database cross-referenced to identify patients with candidaemia

Results 60 patients with Candida BSI (CBSI) Prevalence 0.24 per 1000 patient admissions 55/60 case-notes obtained 38.3% Female Average age 65.2

Evaluation of Candidaemia

Candida Species Breakdown Candida albicans43 (73%) Candida dubliniensis2 (3%) Candida glabrata6 (10%) Candida krusei1 (1%) Candida parapsilosis5 (9%) Candida species (unknown)1 (1%) Candida tropicalis2 (3%)

Reasons for admission 45 Emergency (82%) 10 Elective (18%) – involved complex intra- abdominal surgery

Co-Morbidities Ischaemic Heart Disease 27 (49%) Diabetes Mellitus8 (14.5%) COPD/Asthma10 (18%) Liver2 (4%) Chronic Kidney Disease stage 22 (40%) Stage 1 7 (14%) Stage 2 16 (29.1%) Stage 3 3 (5.5%) Stage 4 1 (2%) Stage 5 6 (10.9%) Unknown including 4 with ARF Malignancy21 (43%)

Risk Factors CVP line37 (67%) Malignancy21 (43%) TPN20 (36%) Hospitalisation within last 30 days19 (35%) Surgery in last 3 months12 (24%) Total days with CVP LineRecorded for 11 (22%), Average of 29 days Immunosuppression/Type6 (11%) IV drug use1 (2%) Past Antifungal exposure1 (2%)

Time to candidaemia after admission 46 cases (84%) occurred after 8 days of admission 21 cases (38%) occurred after greater than 28 days of admission Percentage Diagnosed in ITU: 56% ITU prevalence of 9.4 per 1000 patient admissions Non ITU prevalence 0.10 per 1000 patient admissions Difference ~ 100 fold

Timeliness of Therapy 45 patients (89%) received antifungal treatment within 24 hours of positive culture However mortality was ~ 50% regardless of antifungal administration times Average number of days for a culture to become positive = 2.02 (range 1-4 days)

Treatment Duration No patients had any documented evidence that fundoscopy looking for ocular candidiasis was done Even though this was recommended in writing by the microbiology consultant Only 4 cases had surveillance negative blood cultures after initiation of therapy VITAL to guide treatment duration!

Mortality C. albicansNon-Albicans candida DischargedDeceasedDischargedDeceased Crude Mortality = 37%Crude Mortality = 46% Difference – 9% (not significant p=0.75, Fisher’s exact test) Overall Crude Mortality – 39%

Length of Stay & Cost ITU bed day cost = approximately £2000 and non ITU bed day cost = approximately £300 Total bed days and antifungal costs were –2180 bed days (£48,698/pt) C. albicans group –969 bed days (£67,809/pt) non-albicans candida group Difference in costs between the groups is £19,111/pt Therefore the C. albicans group on average is £19,111/pt cheaper

Limitations Documentation – Some notes missing Transfers Small sample size

Conclusions 89% of patients received appropriate antifungal treatment within 24hours of positive blood culture In very few instances were confirmatory negative blood cultures obtained or fundoscopy performed There is a high mortality rate in patients with Candida BSI Timely antifungal therapy did not influence mortality in our cohort Management cost of C. albicans ~ £19,111/pt cheaper

Recommendations Prevention is key Patients with risk factors for Candida BSI should be placed on empirical antifungal treatment early Fundoscopy should be performed and documented, and confirmatory negative blood cultures obtained from patients on treatment to guide duration Documentation in notes must be CLEAR (this includes ITU notes, for line changes etc) Trust outcome to devise, validate and implement a candidaemia score card to improve outcomes and costs

Action plan Increase awareness of Candida BSI locally (Presented at Trust meetings Summer and Autumn 2011) Incorporate Candida BSI into junior doctor education (Consultant Microbiologist to take forward) Update Trust CVP Policy - including education, training and improving documentation (ICC to take forward) Introduce silver coated CVP lines in ITU (Initiated April 12) Share data with peers and external colleagues (Presented at SEC SHA Antimicrobial Pharmacists Network [Sept 11], UK Federation of Infection Societies Conference [Nov 11] and European Congress of Clinical Microbiology and Infectious Diseases [March 12]) Devise, validate and implement a candidaemia risk score card (Research proposal to be written June 2012)

Questions?