Probiotic therapy in critical illness: does it hold water?

Abstract

We read with interest the recently published article ‘Early and sustained Lactobacillus plantarum probiotic therapy in critical illness: the randomized, controlled, restoration of gut microflora in critical illness trial (ROCIT)’ by Litton et al. [1]. In this multicentre, parallel group, placebocontrolled, randomized clinical trial, the authors enrolled critically ill adults within 48 h of admissions to intensive-care units (ICUs) of 5 hospitals in Australia over 21⁄2 years. They were randomized to receive Lactobacillus plantarum 299v [2 × 1010 colony-forming units (CFUs) per days] (n = 110) or placebo (n = 108) for 60 days. The authors noted that among probiotic and placebo groups, days alive and out of hospital to day 60 [49.5 (37–53) days vs. 49 (43.8–53) days, respectively, p = 0.55]; and rates of nosocomial infections (7.3% vs. 4.6%, p = 0.57) were similar with no side-effects attributable to the probiotic preparation [1]. The paper by Litton et al. [1] is an important contribution to the literature on his topic. As compared to the adult counterparts, the available literature is limited among critically ill children. A double blinded, randomized-controlled trial (RCT) from the authors’ center demonstrated that supplementation with a multi-strain probiotic preparation for 7 days leads to a decrease in the rate of gastrointestinal Candida colonisation by 35%, a reduction in the rate of candiduria by 50%, and a trend toward a lower risk of candidemia [2]. In a retrospective ‘before and after’ study, we demonstrated that the routine use of a multi-strain probiotic preparation for 7 days among critically ill children on broad-spectrum antibiotics resulted in a significant decrease in the rate of candiduria and candidemia [3]. Another RCT from our center demonstrated that enteral administration of a probiotic mix to children with severe sepsis (n = 100) for 7 days resulted in a significant decrease in pro-inflammatory cytokines (IL-6, IL-12p70, IL-17, and TNF-α) and an increase in anti-inflammatory cytokines (IL-10 and TGF-β1) [4]. However, none of these studies demonstrated a beneficial effect on the mortality and duration of ICU stay (2–5), similar to what is noted by Litton et al. [1]. Banupriya et al. [5] conducted an RCT involving critically ill children ≤ 12 years of age (n = 150) who needed mechanical ventilation for > 48 h and randomized them to the intervention group who received probiotics mix for 7 days or till discharge, and to the controls. The intervention group had significantly lower rates of VAP (p < 0.001), duration of PICU (p < 0.001), hospital stay (p = 0.001), and mechanical ventilation (p = 0.001). However, the overall mortality and mortality due to VAP was similar in the two groups. Though some of these studies demonstrated that probiotics hold promise among critically ill children and adults, the answers to several clinically relevant questions are far from reach. Which strain/s is/are to be used? Whether monoor multi-strain preparations are better? What should be the timing, dose, and duration of treatment? Whether probiotics are altogether safe in fragile population of critically ill adults and children? The further research to address these important questions will guide the intensivists regarding whether to use probiotics in critically ill.