Sepsis in early infancy results in one million annual deaths worldwide, most of them in developing countries. No efficient means of prevention is currently available. Here we report on a randomized, double-blind, placebo-controlled trial of an oral synbiotic preparation (Lactobacillus plantarum plus fructooligosaccharide) in rural Indian newborns. We enrolled 4,556 infants that were at least 2,000 g at birth, at least 35 weeks of gestation, and with no signs of sepsis or other morbidity, and monitored them for 60 days. We show a significant reduction in the primary outcome (combination of sepsis and death) in the treatment arm (risk ratio 0.60, 95% confidence interval 0.48-0.74), with few deaths (4 placebo, 6 synbiotic). Significant reductions were also observed for culture-positive and culture-negative sepsis and lower respiratory tract infections. These findings suggest that a large proportion of neonatal sepsis in developing countries could be effectively prevented using a synbiotic containing L. plantarum ATCC-202195.

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Extended-spectrum b-lactamase (ESBL)-producing Gram-negative bacilli (GNB) are of increasing clinical concern in all age groups worldwide. Whilst sepsis continues to be the leading cause of morbidity and mortality in Indian neonates in the community, identification of microbiological attributes in this population is lacking. This population-based study enrolled 1738 infants with a diagnosis of clinical sepsis at four participating centres in India. Each study site conducted Bactec blood culture, identified bacterial species by API test and stored isolates at "70 6C. From 252 GNB isolates, 155 (113 Klebsiella species, 21 Escherichia coli and 21 other) were subjected to drug susceptibility testing, ESBL phenotyping and testing for clonal relatedness of ESBL strains by PFGE. The results demonstrated that Klebsiella species and E. coli are the most common GNB causes of neonatal sepsis in India, and over one-third are ESBL producers in both community and hospital settings. ESBL-producing strains exhibited frequent co-resistance to aminoglycosides and ciprofloxacin, but remained susceptible to imipenem. PFGE analysis revealed extensive genetic diversity within the ESBL-producing isolates, showing multiple profiles (total of 23). Over 40 % of all ESBL-producing isolates formed three pulsed-field profiles (PFP I-III), with PFP-II being the largest cluster (.20 % of all ESBL-producing isolates), sharing strains from two distant locations. Identification of a common clone at two geographically distant centres indicated that predominant clones with increased virulence may exist, even in the absence of any clear outbreak. The presence of ESBL-producing strains in community infants with no prior history of hospitalization or antibiotic use dictates heightened vigilance and further studies on the ecology of these organisms.