Pediatric Critical Care

Critical Care Medicine www.ccmjournal.org 565 C andida is the third most common agent responsible for healthcare-associated bloodstream infections and is the most common agent responsible for invasive fungal infections in children (1, 2). Candidemia is associated with a high mortality and morbidity among hospitalized patients as well as high healthcare costs (3). Prevalence of candidemia has dramatically increased in the past decade (4, 5). Candida species is implicated in 8%–10% of bloodstream infections in PICUs in various studies (6–8). In recent years, we have also witnessed and alarming rise in the prevalence of Candida colonization and candidemia. Colonization by Candida species was seen in 69.2% of patients receiving broad spectrum antibiotics for sepsis or septic shock in our PICU (9), and candidemia was seen in 4.3% of patients (10). Objective: To evaluate the efficacy of probiotics in prevention of Candida colonization in a PICU. Design: Prospective double blinded, randomized controlled trial. Setting: PICU of a tertiary care teaching hospital in north India. Subjects: One hundred fifty children (106 boys, 44 girls), 3 months to 12 yrs old, on broad spectrum antibiotics for at least 48 hrs were randomized using computer-generated random numbers to receive probiotic mix (EUGI) (n = 75) or placebo (n = 75). Intervention: Patients received one sachet twice a day of either probiotics or placebo for 7 days. Probiotics contained Lactobacillus acidophillus, Lactobacillus rhamnosum, Bifidobacterium longum, Bifidobacterium bifidum, Saccharomyces boulardi, Saccharomyces thermophilus, fructo-oligosaccharides; and placebocontained lactose packed in similar-looking sachets. Rectal swabs for fungal culture were taken at day 0, 7, and 14 of enrollment. Primary outcome measure was prevalence of rectal colonization with Candida on day 14 postenrollment; secondary outcomes were growth of Candida in urine (candiduria) and blood (candidemia). Patients were followed until completion of 14 days study period or death of patient. Results: Demographic and clinical variables were comparable in two groups. Prevalence of Candida colonization on day 0 was similar (15 of 75) in both the groups. On day 7, 27.9% (19 of 68) patients in the probiotic group and 42.6% (29 of 68) patients in the placebo group were colonized (relative risk 0.65; 95% confidence interval 0.41–1.05; p = 0.07), whereas, on day 14, colonization was observed in 31.3% (21 of 67) patients in the probiotic group and 50% (34 of 68) in the placebo group (relative risk 0.63; 95% confidence interval 0.41–0.96; p = 0.02). Thus, the relative reduction in prevalence of Candida colonization on day 7 and 14 in the probiotic group was 34.5% and 37.2%, respectively. The increase in number of colonized patients from day 0 to 7 and day 0 to 14 was significant in the placebo group (p = 0.004 and 0.001, respectively) but not in the probiotic group (p = 0.30 and 0.19, respectively; McNemar test). Candiduria was significantly less common in the probiotic group than in the placebo group (17.3% vs. 37.3%; relative risk 0.46; 95% confidence interval 0.26–0.82; p = 0.006). However, prevalence of candidemia did not differ significantly in two groups (1.6% in the probiotic group vs. 6.35% in placebo group; relative risk 0.46; 95% confidence interval 0.08–2.74; p = 0.39). Conclusions: Supplementation with probiotics could be a potential strategy to reduce gastrointestinal Candida colonization and candiduria in critically ill children receiving broad spectrum antibiotics. (Crit Care Med 2013; 41:565–572)