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.

Salmonella enterica subsp. arizonae is a common gut inhabitant of reptiles, with snakes as the most common reservoir. Though human cases due to this organism are exceedingly rare, it may infect young infants and immunocompromised individuals with a history of intimate associations with reptiles. Gastroenteritis is the most common presentation; others include peritonitis, pleuritis, osteomyelitis, meningitis, and bacteremia. We report a fatal case of S. enterica subsp. arizonae gastroenteritis in a 3-month-old child with microcephaly, with a review of earlier cases and problems encountered in identification of this rare human pathogen. CASE REPORTA 3-month-old female child presented to the Emergency Unit at Ram Manohar Lohia Hospital, New Delhi, India, with a history of fever and cough for 20 days and diarrhea with mucus and blood for 15 days. There was no history of similar illness in other family members or in the community. On admission, the child, who had microcephaly, appeared highly irritable and had tachypnea and bilateral crepitations. The spleen and liver were just palpable, and there was a rash all over the body. The patient was diagnosed as having pneumonia with persistent diarrhea. A fecal sample was sent for routine culture and microscopic examination, and the patient was empirically started on broad-spectrum antibiotics (ampicillin, cefotaxime, and amikacin). Investigations revealed a hemoglobin level of 11.0 g%, a total leucocyte count of 11,500/ml, and an erythrocyte sedimentation rate of 100. A urine culture was sterile, and cerebrospinal fluid biochemistry and cytology showed no abnormality. The chest X ray showed infiltration in both lungs, while the skull X ray was normal.The routine microscopic examination of feces did not reveal the presence of any protozoan or helminth. While fecal cultures grew a non-lactose-fermenting motile organism, the routine biochemical tests (indole, triple-sugar iron agar, citrate, urea, mannitol, and motility) for this isolate were obfuscating.

BackgroundNewborn gastrointestinal (GI) tract is considered sterile but rapidly acquires a diverse microbiota from its intimate environment. Early acquisition of a bacterial species in the upper GI tract may play a role in establishing the colonic microbiota. There is paucity of molecular data on the upper GI tract microbiota in preterm neonates.MethodsGastric aspirates from 22 neonates with an average gestational age 27.7 weeks (±2.8), weighing 973.2 grams (±297.9) admitted to a neonatal intensive care unit were collected prospectively from weeks 1-4 of life. All samples were evaluated for microbiota using 16S rRNA-based Denaturing Gradient Gel Electrophoresis. Bacterial species colonization and its association with maternal and neonatal demographics, and neonatal clinical characteristics were analyzed.Results Bacteroides spp. was the predominant species in all four weeks. Bifidobacterium spp. colonization was significantly higher in exclusively breast milk fed compared to partially breast milk (PBM) fed neonates in first (p = 0.03) and third (p = 0.03) week of life. Anaerobic bacteria colonization decreased from first through fourth week of life (p = 0.03). Aerobic bacteria colonization was highly dynamic throughout the four week period. Premature rupture of membrane (p = 0.05) and birth outside of study hospital (p = 0.006) influenced the acquisition of bacteria in the first week of life. Birth weight was positively correlated with total number of bacterial species (p = 0.002) and anaerobes (p = 0.004) in PBM-fed neonates during the fourth week of life. H. pylori and Ureaplasma were not detected in any of our samples.ConclusionGastric bacterial colonization in preterm neonates is unstable during early weeks of life. Delayed oral feeding and use of antibiotics may be responsible for paucity of bacterial species. Monitoring of the gastric microbiota and concurrent examination of stool microbiota may yield important information on the utility of gastric signature patterns for predicting colon microbiota that may drive GI and immune dysfunctions.

Studies of gastrointestinal pathophysiology are not feasible by biopsies in human neonates. We examined the utility of live colonocytes in stool in studying cellular markers during early neonatal life. Expression of IgA, IgG, Cluster of Differentiation-45 cells (CD45), Toll-like receptors-2 and 4 (TLR2, TLR4) were analyzed by flow-cytometry. Colonocyte RNA extracts were used in quantitative RealTime-PCR (qRT-PCR) to examine the expression of cytokeratin-19, ribosomal protein-24, and tight-junction (Tj) protein zonula occludens-1 (ZO-1). Colonocyte yield varied between 5×104 to 2×106 cells/g of stool. Meconium samples yielded a highly enriched population of viable cells. Although low, all samples showed CD45-positive cells during the initial weeks of life. Starting as early as day-2, IgA expression was observed in 69% of the cells. Low to moderate expression of IgG was observed with a linear increase as the infants grew. There was an almost total lack of TLR2 staining; however, over 55% of the colonocytes showed TLR4 expression. While high levels of IgA in gut cells may serve as a natural protectant during neonatal period, increased TLR4 may provide a niche for lipopolysacharide (LPS) mediated epithelial damage. Use of stool colonocytes can be a valuable noninvasive approach for studying gut pathophysiology in the neonatal period.

ObjectiveTo examine the timing and microbiology of neonatal sepsis in a population-based surveillance in the Indian community setting.Study DesignAll live born infants in 223 villages of Odisha state were followed at home for 60 days. Suspect sepsis cases were referred to study hospitals for further evaluation including blood culture.ResultsOf 12,622 births, 842 were admitted with suspected sepsis of whom 95% were 4–60 days old. Culture confirmed incidence of sepsis was 6.7/1000 births with 51% Gram negatives (Klebsiella predominating) and 26% Gram positives (mostly Staphylococcus aureus). A very high level of resistance to penicillin and ampicillin, moderate resistance to cephalosporins, and extremely low resistance to Gentamicin and Amikacin was observed.ConclusionThe bacterial burden of sepsis in the Indian community is not high. Judicious choice of empiric antibiotics, antibiotic stewardship, and alternate modalities should be considered for the management or prevention of neonatal sepsis in India.

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