Role of probiotics in prevention of Candida colonization and invasive candidiasis

We read with interest a recently published study in this journal by Oncel et al. [1] entitled “Comparison of Lactobacillus reuteri (L. reuteri) and nystatin prophylaxis on Candida colonization and infection in very low birth weight (VLBW) infants”. In this prospective, randomized comparative study involving preterm infants (n=300) with a gestational age of ≤32 weeks and birth weight of ≤1500 g, it was concluded that prophylactic orally administered L. reuteri was as effective as nystatin in prevention of fungal colonization and invasive candidiasis (IC). Also, proven sepsis, feeding intolerance, and duration of hospitalization were significantly lower in the probiotics group than in the antifungal group.

This study provided interesting evidence supporting the efficacy of probiotics in prevention of Candida colonization and IC among preterm neonates. However, there are few points in this study that need clarifications and more information from the authors. First, the sample size was calculated on the basis of pre-study incidence of Candida colonization for VLBW neonates in author’s neonatal intensive care unit. Whereas, primary outcomes of this study were to evaluate the effectiveness of L. reuteri compared with nystatin in the prevention of Candida colonization as well as IC. This could have resulted in study being underpowered to make conclusions regarding IC. Second, regarding sample collection, authors stated that skin (axilla, intertriginous and moist area) and stool or rectal cultures were obtained at study enrollment and weekly until discharge; and blood cultures for bacterial and fungal infection were obtained once a week. But in results, the colonization status was depicted as if cultures were obtained only once. What happened to colonization status among the two groups over time is not clear. Also, the time taken for colonization in two groups was not stated. Similarly, the status of IC over time is not clear. So, more information is needed in this regard. Third, it could have been better if blinding have been done by using similar methods of administration of probiotic and nystatin.

Also, we would like to highlight other studies in this field involving preterm neonates and critically ill children. Manzoni et al. [2] in a prospective, randomized clinical trial involving 80 VLBW neonates shown that orally administered L. casei subspecies rhamnosus significantly reduced the incidence and the intensity of enteric colonization by Candida species. Romeo et al. [3] conducted a prospective study involving 249 preterm neonates who were subdivided to receive L. reuteri (n = 83), L. rhamnosus (n = 83), and no supplementation (n = 83). They found that both the probiotics were effective in the prevention of GIT colonization by Candida, in the protection from late-onset sepsis, and in reducing abnormal neurological outcomes. Demirel et al. [4] conducted a prospective, randomized comparative study in preterm infants with a gestational age of ≤32 weeks and birth weight of ≤1500 g. The aim was to compare the efficacy of orally administered Saccharomyces boulardii versus nystatin in prevention of fungal colonization and invasive fungal infections in VLBW infants. They concluded that prophylactic S. boulardii supplementation is as effective as nystatin in reducing fungal colonization and invasive fungal infection, more effective in reducing the incidence of clinical sepsis and number of sepsis attacks and has favorable effect on feeding intolerance. Roy et al. [5] conducted a prospective, randomized, double blind trial involving preterm neonates and revealed that probiotic supplementation (a mix of L. acidophilus, Bifidobacterium longum, B. bifidum and B. lactis) led to reduced enteral fungal colonization, reduced invasive fungal sepsis, earlier establishment of full enteral feeds, and reduced duration of hospital stay. These results were similar to those published by Oncel et al. [1].

Recently, we published a prospective double-blinded, randomized controlled trial [6] from our center to evaluate the efficacy of probiotics in prevention of Candida colonization in critically ill children receiving broad spectrum antibiotics. We found that supplementation with a mix of probiotics (L. acidophillus, L. rhamnosum, B. longum, B. bifidum, S. boulardi and S. thermophilus) for 1 week decreased the prevalence of colonization of GIT with Candida by 34.5% and 37.2% on days 7 and 14, respectively; and almost 50% reduction in incidence of candiduria. Also there was a trend toward a decrease in the risk of candidemia in probiotic group, although the difference did not reach significance since the study was underpowered for this outcome. Thereafter, we conducted a retrospective “before and after” study [7] and found that routine use of probiotics in critically ill children receiving broad-spectrum antibiotics resulted in significant reduction in incidence of candidemia and candiduria.

Results of all the above studies suggest a clear role of probiotics in prevention of Candida colonization and IC not only among preterm neonates but also in critically ill children. A discussion on likely mechanisms by which probiotics may help in prevention of Candida infection can be found in a recently published review [8]. Well-designed multicentric clinical studies are needed regarding efficacy, safety, dose, duration and strains (type and single or combination of different strains) of probiotics in prevention of Candida colonization and IC before any practice guidelines can be established in this field.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.