Implementing Fluconazole Prophylaxis and Antibiotic Stewardship in a Burn Unit—Impact on Fungal Infection and Mortality

Background: Disseminated fungal infection (DFI)is an often fatal complication of patients with major burns,.   Risk factors for DFI include high BSA burn, extensive use of broad spectrum antibiotics, granulocytopenia,  hyperalimentation, and host immune defects.  Early diagnosis of DFI is difficult because since most non-yeast organisms do not grow in blood cultures.  The Johns Hopkins Burn Unit (JHBU) has >400 admissions annually; and 20% have >20% total body surface area burns.  In 2005, our Burn Unit initiated routine fluconazole prophylaxis (400 mg daily enterally) for all critically ill patients; adopted a rigorous antimicrobial stewardship policy , and discontinued routine prophylactic broad spectrum antibiotics.
Objective: In this retrospective analysis, we compared fungal disease outcomes in the pre-intervention (1/02-8/05) and post-intervention (9/05-6/09) periods.

Methods: All deaths and fungal culture results were evaluated for the study periods.  Deaths were evaluated for presence of skin or tissue evidence of disseminated fungal disease. Disseminated fungal infection were  defined as patients with positive cultures from sterile sites or multiple positive cultures from distant non-sterile sites in the presence of systemic illness and source. Incidence rates are calculated per 1000 JHBU patient-days (pds).  Odds ratios (OR) are presented to reflect intervention impact.
Results: Patient demographics of the two study periods were similar and included average age 58.9 vs 58.5, length of stay (15.5 vs 16.3), average BSA burn (51% vs 52%). Pre and post-intervention overall mortality rates were 8.7 and 5.5 per 1000pds (Intervention OR=0.63, 95%CI=0.44-0.90). Death rates with definitive DFI were 0.79 pre-intervention and 0.27 post-intervention per 1000pds (OR=0.34; 95%CI:0.07-1.52). Incident rates of patients with ≥1 cultures positive for Candida fell from 2.2 pre-intervention to 0.4 post-intervention per 1000pds (OR= 0.24; 95%CI:0.08-0.65). Non-yeast infections (i.e molds) also decreased in the latter period but the difference was not significant

Conclusions: Fluconazole prophylaxis and antibiotic stewardship significantly decreases incidence of candidiasis among critically ill patients in the burn ICU setting . There was a trend towards decreased mortality.