Towards understanding global patterns of antimicrobial use and resistance in neonatal sepsis: insights from the NeoAMR network.

OBJECTIVE: To gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR). DESIGN: A web-based survey using a REDCap database was circulated to NNUs participating in the Neonatal AMR research network. The survey included questions about NNU funding structure, size, admission rates, access to supportive therapies, empirical antimicrobial guidelines and period prevalence of neonatal blood culture isolates and their resistance patterns. SETTING: 39 NNUs from 12 countries. PATIENTS: Any neonate admitted to one of the participating NNUs. INTERVENTIONS: This was an observational cohort study. RESULTS: The number of live births per unit ranged from 513 to 27 700 over the 12-month study period, with the number of neonatal cots ranging from 12 to 110. The proportion of preterm admissions <32 weeks ranged from 0% to 19%, and the majority of units (26/39, 66%) use Essential Medicines List 'Access' antimicrobials as their first-line treatment in neonatal sepsis. Cephalosporin resistance rates in Gram-negative isolates ranged from 26% to 84%, and carbapenem resistance rates ranged from 0% to 81%. Glycopeptide resistance rates among Gram-positive isolates ranged from 0% to 45%. CONCLUSION: AMR is already a significant issue in NNUs worldwide. The apparent burden of AMR in a given NNU in the LMIC setting can be influenced by a range of factors which will vary substantially between NNUs. These variations must be considered when designing interventions to improve neonatal mortality globally

Flavor and Antioxidant Capacity of Peanut Paste and Peanut Butter Supplemented with Peanut Skins

Peanut skins (PS) are a good source of phenolic compounds. This study evaluated antioxidant properties and flavor of peanut paste and peanut butter enhanced with peanut skins. PS were added to both materials in concentrations of 0.0%, 0.5%, 1.0%, 5.0%, 10.0%, 15.0%, and 20.0% (w/w). PS, peanut paste, and peanut butter used in the study had initial total phenolics contents of 158, 12.9, and 14.1 mg GAE/g, respectively. Hydrophilic oxygen radical absorbance capacity (H-ORAC) of peanut skins was 189453 μMol Trolox/100 g and addition of 5% PS increased H-ORAC of peanut paste and peanut butter by 52% to 63%. Descriptive sensory analysis indicated that the addition of 1% PS did not change intensity of descriptors in the sensory profile of either peanut paste or peanut butter. Addition of 5% PS resulted in significant differences in woody, hulls, skins; bitter; and astringent descriptors and 10% PS addition resulted in significant differences in most attributes toward more negative flavor

Changing trend in bacterial etiology and antibiotic resistance in sepsis of intramural neonates at a tertiary care hospital

Background: Septicemia is an important cause of neonatal morbidity and mortality. However, organized data on causative organisms and their resistant pattern are scanty from developing countries. The changing trend in causative organisms and their antibiotic resistance is yet to be documented in India. The present study examines the trends in bacterial profile and antibiotic resistance of the organisms causing sepsis in hospitalized neonates. Materials and Methods: A retrospective laboratory-based analysis of blood cultures obtained from Neonatal Intensive Care Unit of a tertiary care hospital in New Delhi was done for the period of 1999–2014, divided into five phases. Results: A total of 4700 isolates were considered. Over time, Gram-negative organisms have replaced Gram-positives as frequent isolates. Initially, there was predominance of Klebsiella pneumoniae, then of Staphylococcus aureus which recently has been changed with coagulase negative-Staphylococcus and Acinetobacter. Growing resistance against the first and second line of drugs has been noted, including methicillin-resistant S. aureus and vancomycin-resistant Enterococcus. Conclusion: The etiological profile of neonatal sepsis has changed tremendously in the past 15 years. High resistance against common drugs necessitates continued surveillance and review of empirical antibiotic policy for neonatal sepsis. These steps are important to effectively curtail the surge of further antibiotic resistance

Effect of vitamin D supplementation of low birth weight term Indian infants from birth on cytokine production at 6 months.

BACKGROUND/OBJECTIVES: Vitamin D deficiency has been associated with impaired resistance to infection, which may be mediated by alterations in cytokine responses. We investigated the effect of vitamin D supplementation to infants on whole blood in-vitro cytokine production and on the inflammatory marker, plasma C-reactive protein (CRP). SUBJECTS/METHODS: Blood samples were taken at 6 months of age from infants participating in the DIVIDS (Delhi Infant Vitamin D Supplementation) randomized controlled trial of weekly vitamin D supplements (1400 IU = recommended intake) from birth to 6 months with the aim of decreasing mortality and severe morbidity. We measured plasma CRP and whole blood in-vitro production of tumour necrosis factor-α (TNFα), interferon-γ (INFγ), interleukin (IL)-10 and IL-13 following no stimulation or stimulation with lipopolysaccharide or phytohemagglutinin. RESULTS: Although the intervention improved vitamin D status in a severely deficient population, there were no differences between treatment groups in plasma CRP or in the production of any of the cytokines in either unstimulated or stimulated cultures. Recent illness had limited association with immunological markers. Plasma 25-hydroxyvitamin D levels were not associated with CRP or production of any cytokines. CONCLUSIONS: Vitamin D supplementation did not affect plasma CRP or whole blood cytokine production of vitamin D-deficient low birth weight infants. This is consistent with the lack of effect of vitamin D on mortality and severe morbidity among infants in the DIVIDS trial

Leakage and lysis of lipid membranes induced by the lipopeptide surfactin

Surfactin is a lipopeptide produced by Bacillus subtilis which possesses antimicrobial activity. We have studied the leakage and lysis of POPC vesicles induced by surfactin using calcein fluorescence de-quenching, isothermal titration calorimetry and (31)P solid state NMR. Membrane leakage starts at a surfactin-to-lipid ratio in the membrane, R (b) approximately 0.05, and an aqueous surfactin concentration of C (S) (w) approximately 2 microM. The transient, graded nature of leakage and the apparent coupling with surfactin translocation to the inner leaflet of the vesicles, suggests that this low-concentration effect is due to a bilayer-couple mechanism. Different permeabilization behaviour is found at R (b) approximately 0.15 and attributed to surfactin-rich clusters, which can induce leaks and stabilize them by covering their hydrophobic edges. Membrane lysis or solubilization to micellar structures starts at R (b) (sat) = 0.22 and C (S) (w) = 9 microM and is completed at R (m) (sol) = 0.43 and C (S) (w) = 11 microM. The membrane-water partition coefficient of surfactin is obtained as K = 2 x 10(4) M(-1). These data resolve inconsistencies in the literature and shed light on the variety of effects often referred to as detergent-like effects of antibiotic peptides on membranes. The results are compared with published parameters characterizing the hemolytic and antibacterial activity

Clinico-epidemiological profile and predictors of severe illness in young infants (&#60; 60 days) reporting to a hospital in North India

Objectives: To describe the clinical and epidemiological profile of young infants reporting to a hospital and assess previously proposed simple clinical signs for their value in enabling health workers to detect young infants with severe illness warranting hospital admission. Methods: Observational study of infants less than 2 months of age presenting consecutively to a large public hospital in South Delhi who were evaluated by a health worker (nurse), on a standardized list of signs and symptoms, and the ability of these were evaluated against the need for hospital admission which was assessed by an independent pediatrician. Results: Of the 1624 young infants triaged, 878 were enrolled into the study. Of these 100 (11%) were below 7 days of age, for whom the common reasons for seeking care were jaundice (52%), not feeding well (6%) and fever (5%). The remaining 778 (89%) were 7-59 days of age with respiratory symptoms as the main presenting complaints (29.1 %). The primary clinical diagnoses in infants with serious illness needing admission to hospital in the age group &#60; 7 days (n = 66) were hyperbilirubinemia (56%) and sepsis (21%). In those between 7-27 days of age (n = 60), primary diagnoses were sepsis (27%), pneumonia (13%), diarrhea, dysentery or dehydration (10%), while in the age group 28-59 days of age (n = 47) pneumonia (40%), sepsis (19%) and diarrhea or dehydration (13%) were the common primary diagnoses. Signs that had at least a prevalence of 5% and were strong predictors for all the age categories studied were history of difficult feeding (OR 6.8 for 0-6 days, 15.1 for 2-27 days and 6.2 for 28-59 days age groups), not feeding well on observation (OR 13.7, 27.6 and 20.9 respectively for the 3 age groups), temperature >37.5ºC (OR 21.8, 14.6 and 30.0 respectively for the 3 age groups) and respiratory rate >60 per minute (OR 6.8, 15.1 and 21.0 respectively for the 3 age groups). Additional strong predictors with >5% prevalence were history of convulsions (OR 7.9, only in 0-6 day age group), lethargy (OR 26.1, only in 7-27 day age group), and history of diarrhea (OR 3.0 for 2-27 days and 2.2 for 28-59 days age groups). Conclusions: Simple clinical signs are useful in hands of health worker for identifying neonates with serious illness warranting hospital admission. These will be of use in the further development of clinical algorithms for the national integrated management of childhood illnesses

Differences in multiple immune parameters between Indian and U.S. infants.

To compare immune phenotypes across two geographic and ethnic communities, we examined umbilical cord blood by flow cytometry and Luminex in parallel cohorts of 53 newborns from New Delhi, India, and 46 newborns from Stanford, California. We found that frequencies of a B cell subset suggested to be B-1-like, and serum IgM concentration were both significantly higher in the Stanford cohort, independent of differences in maternal age. While serum IgA levels were also significantly higher in the Stanford cohort, IgG1, IgG2, and IgG4 were significantly higher in the New Delhi samples. We found that neutrophils, plasmacytoid dendritic cells, CD8+ T cells, and total T cells were higher in the U.S. cohort, while dendritic cells, patrolling monocytes (CD14dimCD16+), natural killer cells, CD4+ T cells, and naïve B cells were higher in the India cohort. Within the India cohort, we also identified cell types whose frequency was positively or negatively predictive of occurrence of infection(s) in the first six months of life. Monocytes, total T cells, and memory CD4+ T cells were most prominent in having an inverse relationship with infection. We suggest that these data provide impetus for follow-up studies linking phenotypic differences to environmental versus genetic factors, and to infection outcomes