Effectiveness of BNT162b2 Vaccination During Pregnancy in Preventing Hospitalization for Severe Acute Respiratory Syndrome Coronavirus 2 in Infants.

OBJECTIVE: To assess the clinical effectiveness of the BNT162b2 vaccine during pregnancy in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hospitalizations of infants. STUDY DESIGN: A retrospective, multicenter, 1:3 case-control (test-negative) study. Symptomatic hospitalized infants less than 6 months of age, with a positive SARS-CoV-2 polymerase chain reaction test between January 3, 2021, and March 11, 2021, were matched by age and time to negative controls, hospitalized with symptoms compatible with SARS-CoV-2 infection. Mothers were defined as fully vaccinated who received 2 doses of BNT162b2 with the second given 2 weeks to 6 months before delivery; or partially vaccinated, if they received only 1 dose or 2 doses with the second given more than 6 months or less than 2 weeks before delivery. Severe SARS-CoV-2 was defined as a need for assisted ventilation. RESULTS: We matched 116 SARS-CoV-2 positive infants with 348 negative controls with symptoms compatible with SARS-CoV-2 infection. The effectiveness of fully vaccinated mothers was 61.6% (95% CI, 31.9-78.4) and the effectiveness of partially vaccinated mothers was not significant. Effectiveness was higher in infants 0-2 vs 3-6 months of age. The effectiveness (57.1%; 95% CI, 22.8-76.4) was similar when excluding mothers who were infected with SARS-CoV-2 during pregnancy. The OR of severe infection in infants born to unvaccinated vs fully vaccinated mothers was 5.8. CONCLUSIONS: At least 2 doses of BNT162b2 vaccine administered during the second or third trimester of pregnancy had an effectiveness of 61.6% in decreasing hospitalization for SARS-CoV-2 infection in infants less than 6 months of age.

Early exposures and inherent factors in premature newborns are associated with type 1 diabetes.

BACKGROUND: Pathophysiology of type 1 diabetes (T1D) involves immune responses that may be associated with early exposure to environmental factors among preterm newborns. The aim of this work was to evaluate for association between T1D and maternal, nutritional, and medical exposures during the neonatal period among premature newborns. METHODS: This is a multicenter, matched case-control study. Preterm newborns, who developed T1D before 18 years, were matched by sex, gestational age (GA), birth date, and medical center of birth with newborns who did not develop TID. Data included maternal medical history, birth weight (BW), length of hospitalization, enteral and parenteral medications, fluid administration, and feeding modalities during hospitalization. RESULTS: Fifty-two patients with T1D, 26 males, median age at T1D diagnosis 8.17 years (5.92-9.77), median GA 34 weeks (33-m36), and 132 matched controls, were included. Multivariate-conditional-regression demonstrated a significant association between T1D and any maternal illness (23.1% vs. 9.1%, OR = 4.99 (1.69-14.72), p = 0.004), higher BW-SDS (0.07 ± 0.95 vs. -0.27 ± 0.97, OR = 2.03 (1.19-3.49), p = 0.01), longer duration of glucose infusion (3 (1-5) days vs. 2 (0-4), OR = 1.23 (1.03-1.46), p = 0.02), and antibiotic therapy beyond the first week of life (19.2% vs. 6.9%, OR = 5.22 (1.32-20.70), p = 0.019). Antibiotic treatment during the first week of life was negatively associated with T1D (51.9% vs. 67.2%, OR 0.31 (0.11-0.88), p = 0.027). CONCLUSIONS: A novel association was demonstrated between the development of T1D and early interventions and exposures among preterm newborns. IMPACT: Type 1 diabetes mellitus during childhood may be associated with early exposures during the neonatal period, in addition to known maternal and neonatal metabolic parameters. Early exposure to intravenous antibiotics, differing between the first week of life and later, and longer parenteral glucose administration to preterm newborns were associated with childhood type 1 diabetes. This is in addition to familiar maternal risk factors. Future prospective studies should examine the microbial changes and immune system characteristics of preterm and term neonates exposed to parenteral antibiotics and glucose treatment, in order to validate our exploratory findings.

Medical Masks Versus N95 Respirators for Preventing COVID-19 Among Health Care Workers : A Randomized Trial.

BACKGROUND: It is uncertain if medical masks offer similar protection against COVID-19 compared with N95 respirators. OBJECTIVE: To determine whether medical masks are noninferior to N95 respirators to prevent COVID-19 in health care workers providing routine care. DESIGN: Multicenter, randomized, noninferiority trial. (ClinicalTrials.gov: NCT04296643). SETTING: 29 health care facilities in Canada, Israel, Pakistan, and Egypt from 4 May 2020 to 29 March 2022. PARTICIPANTS: 1009 health care workers who provided direct care to patients with suspected or confirmed COVID-19. INTERVENTION: Use of medical masks versus fit-tested N95 respirators for 10 weeks, plus universal masking, which was the policy implemented at each site. MEASUREMENTS: The primary outcome was confirmed COVID-19 on reverse transcriptase polymerase chain reaction (RT-PCR) test. RESULTS: In the intention-to-treat analysis, RT-PCR-confirmed COVID-19 occurred in 52 of 497 (10.46%) participants in the medical mask group versus 47 of 507 (9.27%) in the N95 respirator group (hazard ratio [HR], 1.14 [95% CI, 0.77 to 1.69]). An unplanned subgroup analysis by country found that in the medical mask group versus the N95 respirator group RT-PCR-confirmed COVID-19 occurred in 8 of 131 (6.11%) versus 3 of 135 (2.22%) in Canada (HR, 2.83 [CI, 0.75 to 10.72]), 6 of 17 (35.29%) versus 4 of 17 (23.53%) in Israel (HR, 1.54 [CI, 0.43 to 5.49]), 3 of 92 (3.26%) versus 2 of 94 (2.13%) in Pakistan (HR, 1.50 [CI, 0.25 to 8.98]), and 35 of 257 (13.62%) versus 38 of 261 (14.56%) in Egypt (HR, 0.95 [CI, 0.60 to 1.50]). There were 47 (10.8%) adverse events related to the intervention reported in the medical mask group and 59 (13.6%) in the N95 respirator group. LIMITATION: Potential acquisition of SARS-CoV-2 through household and community exposure, heterogeneity between countries, uncertainty in the estimates of effect, differences in self-reported adherence, differences in baseline antibodies, and between-country differences in circulating variants and vaccination. CONCLUSION: Among health care workers who provided routine care to patients with COVID-19, the overall estimates rule out a doubling in hazard of RT-PCR-confirmed COVID-19 for medical masks when compared with HRs of RT-PCR-confirmed COVID-19 for N95 respirators. The subgroup results varied by country, and the overall estimates may not be applicable to individual countries because of treatment effect heterogeneity. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, World Health Organization, and Juravinski Research Institute.

Effects of Diet-Modulated Autologous Fecal Microbiota Transplantation on Weight Regain.

BACKGROUND & AIMS: We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight-loss phase. METHODS: In the DIRECT PLUS (Dietary Intervention Randomized Controlled Trial Polyphenols-Unprocessed) weight-loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to healthy dietary guidelines, Mediterranean diet, and green-Mediterranean diet weight-loss groups. All groups received free gym membership and physical activity guidelines. Both isocaloric Mediterranean groups consumed 28 g/d walnuts (+440 mg/d polyphenols provided). The green-Mediterranean dieters also consumed green tea (3-4 cups/d) and a Wolffia globosa (Mankai strain, 100 g/d) green shake (+800 mg/d polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque, and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight-regain phase (months 6-14). Secondary outcomes were gastrointestinal symptoms, waist circumference, glycemic status, and changes in the gut microbiome, as measured by metagenomic sequencing and 16s ribosomal RNA. We validated the results in a parallel in vivo study of mice specifically fed with Mankai compared with control chow diet. RESULTS: Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules during the transplantation period. No aFMT-related adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6-14 (aFMT, 30.4% vs placebo, 40.6%; P = .28), aFMT significantly attenuated weight regain in the green-Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P = .02), but not in the dietary guidelines (P = .57) or Mediterranean diet (P = .64) groups (P for the interaction = .03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89 cm vs placebo, 5.05 cm; P = .01) and insulin rebound (aFMT, -1.46 ± 3.6 µIU/mL vs placebo, 1.64 ± 4.7 µIU/mL; P = .04) in the green-Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction = .04 and .03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight-loss phase, and to prompt preservation of weight-loss-associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) after the aFMT. In mice, Mankai-modulated aFMT in the weight-loss phase compared with control diet aFMT, significantly prevented weight regain and resulted in better glucose tolerance during a high-fat diet-induced regain phase (all, P < .05). CONCLUSIONS: Autologous FMT, collected during the weight-loss phase and administrated in the regain phase, might preserve weight loss and glycemic control, and is associated with specific microbiome signatures. A high-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure. ClinicalTrials.gov number, NCT03020186.

Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial.

OBJECTIVE: To examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/processed meat, and enriched with green plants and polyphenols on non-alcoholic fatty liver disease (NAFLD), reflected by intrahepatic fat (IHF) loss. DESIGN: For the DIRECT-PLUS 18-month randomized clinical trial, we assigned 294 participants with abdominal obesity/dyslipidaemia into healthy dietary guidelines (HDG), MED and green-MED weight-loss diet groups, all accompanied by physical activity. Both isocaloric MED groups consumed 28 g/day walnuts (+440 mg/day polyphenols provided). The green-MED group further consumed green tea (3-4 cups/day) and Mankai (a Wolffia globosa aquatic plant strain; 100 g/day frozen cubes) green shake (+1240 mg/day total polyphenols provided). IHF% 18-month changes were quantified continuously by proton magnetic resonance spectroscopy (MRS). RESULTS: Participants (age=51 years; 88% men; body mass index=31.3 kg/m2; median IHF%=6.6%; mean=10.2%; 62% with NAFLD) had 89.8% 18-month retention-rate, and 78% had eligible follow-up MRS. Overall, NAFLD prevalence declined to: 54.8% (HDG), 47.9% (MED) and 31.5% (green-MED), p=0.012 between groups. Despite similar moderate weight-loss in both MED groups, green-MED group achieved almost double IHF% loss (-38.9% proportionally), as compared with MED (-19.6% proportionally; p=0.035 weight loss adjusted) and HDG (-12.2% proportionally; p<0.001). After 18 months, both MED groups had significantly higher total plasma polyphenol levels versus HDG, with higher detection of Naringenin and 2-5-dihydroxybenzoic-acid in green-MED. Greater IHF% loss was independently associated with increased Mankai and walnuts intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, changes in microbiome composition (beta-diversity) and specific bacteria (p<0.05 for all). CONCLUSION: The new suggested strategy of green-Mediterranean diet, amplified with green plant-based proteins/polyphenols as Mankai, green tea, and walnuts, and restricted in red/processed meat can double IHF loss than other healthy nutritional strategies and reduce NAFLD in half. TRIAL REGISTRATION NUMBER: NCT03020186.

Presence of SARS-CoV-2 RNA on playground surfaces and water fountains.

The possibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission by fomites or environmental surfaces has been suggested. It is unclear if SARS-CoV-2 can be detected in outdoor public areas. The objective of the current study was to assess the presence of SARS-CoV-2 in environmental samples collected at public playgrounds and water fountains, in a country with high disease prevalence. Environmental samples were collected from six cities in central Israel. Samples were collected from drinking fountains and high-touch recreational equipment at playgrounds. Sterile pre-moistened swabs were used to collect the samples, put in viral transfer media and transferred to the laboratory. Viral detection was achieved by real-time reverse transcriptase-polymerase chain reaction, targeting four genes. Forty-three samples were collected from playground equipment and 25 samples from water fountains. Two of the 43 (4.6%) samples from playground equipment and one (4%) sample from a drinking fountain tested positive. It is unclear whether the recovery of viral RNA on outdoor surfaces also indicates the possibility of acquiring the virus. Adherence to environmental and personal hygiene in urban settings seems prudent.

Fever response to ibuprofen in viral and bacterial childhood infections.

OBJECTIVE: to compare the antipyretic effects of ibuprofen in febrile children with serious bacterial infections (SBI), and children with a presumed viral infection. METHODS: A prospective cross- sectional study was conducted in a pediatric Emergency department between October 2018 and March 2020 for children aged 3 months to 4 years with a rectal temperature ≥ 38.5 °C. Patients received 10 mg/kg of ibuprofen oral suspension. Rectal temperature was measured 60 and 120 min after administration. Laboratory and imaging evaluations were performed for each study participant in order to identify serious bacterial infection. RESULTS: Ninety patients were included, of which 18 were diagnosed with serious bacterial infections. There was no significant difference in age, fever at presentation and duration of fever between the groups. No significant difference was noted in body temperature reduction at 60 and 120 min after ibuprofen administration (1.09 ± 0.75 °C vs 0.89 ± 0.58 °C, mean difference -0.12 °C, 95% CI -0.54-0.15 °C; 1.85 ± 0.53 °C vs 1.78 ± 0.83 °C, mean difference - 0.07 °C, 95% CI -0.49-0.36 °C, in the SBI and non-SBI groups respectively). CONCLUSION: Fever response to Ibuprofen administration is not indicative of serious bacterial infections in children under 4 years of age. Larger prospective studies are required to define whether the lack of response to Ibuprofen has any impact on the management of febrile children.

Children discharged from an emergency department with bacteraemia had lower C-reactive protein and better outcomes than admissions.

AIM: To investigate whether there are common clinical findings in bacteraemic children that were discharged from the emergency department (ED) and to follow their clinical outcome. METHODS: A retrospective chart review of children above one-month-old with positive blood cultures obtained in Shamir Medical Center's ED between January 2011 and December 2019 was conducted. RESULTS: A total of 250 cases were analysed, of which 68 discharged after first evaluation. Streptococcus pneumonia was the most commonly isolated pathogen. Compared to children that were admitted when first evaluated in the ED, discharged children had lower C-reactive protein (mean 50.5 ± 62.8 vs 121.7 ± 113.2 mg/L, p < 0.001). Dyspnoea and being ill-looking were less prevalent among the latter (6.7% versus 35.1%, p = <0.001, 3.0% versus 22.2% p < 0.001, respectively), as were presence of Kingella kingae and other Gram-negative bacteria. Of the children hospitalised in our institution, the duration of hospitalisation was significantly lower than in those admitted during the first visit (6.3 ± 4.3 vs 9.0 ± 7.4 days, p = .002). None of the discharged children were admitted to paediatric intensive care unit. CONCLUSION: Children with bacteraemia who were discharged home before knowing their positive blood cultures results had lower C-reactive protein and better outcome compared to those admitted on first evaluation in emergency department.

Benign course and clinical features of COVID-19 in hospitalised febrile infants up to 60 days old.

AIM: Minimal data exist regarding the severity of COVID-19 in febrile infants under 60 days old. This multicentre prospective study explored the clinical course and outcomes of this hospitalised patient population, as, to date, the best approach has not been specifically addressed. METHODS: This study focused on the clinical features, laboratory parameters and outcomes of febrile infants up to 60 days old who tested positive for the virus and were hospitalised in Israel from March 2020 to January 2021. The data were extracted from a real-time prospective surveillance network for COVID-19 that includes 20 of the country's 26 hospitals. RESULTS: We identified 75 febrile young infants (60% female) with COVID-19 at a median age of 28 days (range 8-56 days). Of these, 84% had an unremarkable medical history, 29% had respiratory symptoms, and 96% had a mild illness. The Rochester criteria showed that 44% were considered at high-risk for serious bacterial infections, and we found that eight infants actually had concomitant bacterial infections. Outcomes were excellent, and no complications or fatalities were reported. CONCLUSION: The excellent outcomes of young febrile infants with COVID-19 closely resembled other respiratory viral aetiologies of fever in this age group, and there were no fatalities.

The prevalence and underreporting of needlestick injuries among hospital workers: a cross-sectional study.

OBJECTIVE: Needlestick and sharps injuries (NSIs) are known occupational risks among health-care workers. Reporting these injuries is important for early prevention and management of blood-borne infections. We investigated the prevalence and characteristics of NSIs and underreporting among hospital workers (HWs) from different sectors. METHODS: A single-center cross-sectional study, involving an anonymous survey delivered to 2205 HWs. The survey included demographic information about the worker and information about training, injuries and reporting. RESULTS: Of the 844 HWs respondents (40%), NSIs occurred in 443 of them (53%); the majority were from needles (68%) and at bedside (51%). Significantly higher prevalences of injuries (P < 0.001) were noted among physicians (75%) and workers in their 40s (61%) and in the emergency and surgical departments (66% and 55%, respectively). NSIs were reported among 28% of workers who did not directly use needles. Underreporting was found in 46%, with a significant decrease in the report rate as the number of injuries increased (P < 0.001). Underreporting was significantly more common (P < 0.001) among physicians (59%), especially seniors (72%), workers without training about NSIs (59%), older age groups (56% in workers above 51 years, P = 0.003) and males (54%, P = 0.01). The highest underreporting rate was in injuries occurring in the operating room and the lowest in witnessed injuries occurring while passing a needle (82% vs. 31%, P < 0.001). CONCLUSIONS: NSIs and underreporting are common among HWs from all sectors, including those who do not use needles. Improving preventive measures and reporting should be encouraged. We recommend reducing bedside procedures as possible and assigning two workers to procedures at risk for injuries, to increase the report rate.

Maternal vaccinations coverage and reasons for non-compliance - a cross-sectional observational study.

BACKGROUND: Maternal influenza and pertussis vaccinations have been proven safe and effective in reducing maternal and infant morbidity and mortality. Though recommended, not all pregnant women receive these important vaccines. We aimed to evaluate the vaccine coverage of maternal immunization in pregnancy for seasonal influenza and acellular pertussis and elucidate the reasons for non-vaccination among pregnant women. The secondary objective was to describe factors that affect vaccine uptake. METHODS: A cross sectional observational study using anonymous questionnaires distributed to women in the maternity ward or pregnant women hospitalized in the high-risk ward, between Nov 2017 and June 2018, In an Israeli tertiary hospital. RESULTS: Of 321 women approached, 313 were eligible, with a total of 290 women completing the questionnaire (92.6%). We found a 75.9% (95% CI 71-81) and 34.5% (95% CI 29-40) vaccination rate for pertussis and influenza vaccines, respectively. The most prominent reason for not receiving the pertussis vaccine was being under-informed (24%). Influenza vaccine was not received mainly due to concerns about vaccine efficacy (28%). Other factors influencing vaccine uptake included education, prior childbirth and vaccine recommendations made by the provider. CONCLUSION: Although maternal vaccination of pertussis and influenza is officially recommended, vaccine uptake is suboptimal. Our study suggests a central role for medical providers in diminishing the concerns about safety and efficacy, and presents novel factors influencing compliance rates, like seasonality and number of prior births.

A Green-Mediterranean Diet, Supplemented with Mankai Duckweed, Preserves Iron-Homeostasis in Humans and Is Efficient in Reversal of Anemia in Rats.

BACKGROUND: Decreased dietary meat may deplete iron stores, as plant-derived iron bioavailability is typically limited. OBJECTIVES: We explored the effect of a low-meat Mediterranean (green-MED) diet, supplemented with Wolffia globosa duckweed (Mankai: rich in protein and iron) as a food source for humans, on iron status. We further examined the iron bioavailability of Mankai in rats. METHODS: Two hundred and ninety-four abdominally obese/dyslipidemic [mean age = 51.1 y; body mass index (kg/m2) = 31.3; 88% men] nonanemic participants were randomly assigned to physical activity (PA), PA + MED diet, or PA + green-MED diet. Both isocaloric MED groups consumed 28 g walnuts/d and the low-meat green-MED group further consumed green tea (800 mL/d) and Mankai (100 g green shake/d). In a complementary animal experiment, after 44 d of an iron deficiency anemia-inducing diet, 50 female rats (age = 3 wk; Sprague Dawley strain) were randomly assigned into: iron-deficient diet (vehicle), or vehicle + iso-iron: ferrous gluconate (FG) 14, Mankai 50, and Mankai 80 versions (1.7 mg · kg-1 · d-1 elemental iron), or FG9.5 and Mankai 50-C version (1.15 mg · kg-1 · d-1 elemental iron). The specific primary aim for both studies was changes in iron homeostasis parameters. RESULTS: After 6 mo of intervention, iron status trajectory did not differ between the PA and PA + MED groups. Hemoglobin modestly increased in the PA + green-MED group (0.23 g/dL) compared with PA (-0.1 g/dL; P < 0.001) and PA + MED (-0.1 g/dL; P < 0.001). Serum iron and serum transferrin saturation increased in the PA + green-MED group compared with the PA group (8.21 µg/dL compared with -5.23 µg/dL and 2.39% compared with -1.15%, respectively; P < 0.05 for both comparisons), as did folic acid (P = 0.011). In rats, hemoglobin decreased from 15.7 to 9.4 mg/dL after 44 d of diet-induced anemia. After depletion treatment, the vehicle-treated group had a further decrease of 1.3 mg/dL, whereas hemoglobin concentrations in both FG and Mankai iso-iron treatments similarly rebounded (FG14: +10.8 mg/dL, Mankai 50: +6.4 mg/dL, Mankai 80: +7.3 mg/dL; FG9.5: +5.1 mg/dL, Mankai 50-C: +7.1 mg/dL; P < 0.05 for all vs. the vehicle group). CONCLUSIONS: In humans, a green-MED low-meat diet does not impair iron homeostasis. In rats, iron derived from Mankai (a green-plant protein source) is bioavailable and efficient in reversal of anemia. This trial was registered at clinicaltrials.gov as NCT03020186.

Predictors of grade 3-5 vesicoureteral reflux in infants ≤ 2 months of age with pyelonephritis.

BACKGROUND: This study aimed to assess predictors for grade 3-5 vesicoureteral reflux (VUR) in infants ≤ 2 months of age admitted for first urinary tract infection (UTI). METHODS: Retrospective cohort study of 195 infants ≤ 2 months admitted to a pediatric ward for first UTI between 2006 and 2017. Clinical, laboratory, and imaging data were collected from electronic medical charts. We examined associations between grade 3-5 VUR and different patient characteristics. RESULTS: Twenty infants (10%) were diagnosed with grade 3-5 VUR; all had fever. Infants with grade 3-5 VUR had higher blood neutrophil percentage (BNP) (65% vs. 46%, P < 0.001), higher neutrophil-to-lymphocyte ratio (NLR) (2.6 vs. 1.3, P < 0.001), more renal ultrasound abnormalities (prenatal 26% vs. 5%, P = 0.007; postnatal 84% vs. 55%, P = 0.015), and Pseudomonas UTI (15% vs. 1%, respectively, P < 0.001). NLR > 1.65 showed sensitivity 100% and specificity 61% for detecting grade 3-5 VUR. BNP > 53% showed sensitivity 100% and specificity 60% for detecting grade 3-5 VUR. BNP was the best single marker for grade 3-5 VUR with area under the curve (AUC) of 0.82 (95% CI 0.75-0.89). In a multivariate model, AUC for combination of BNP and hydronephrosis was 0.86 (95% CI 0.79-0.93, P = 0.007). CONCLUSIONS: Infants ≤ 2 months of age admitted for a first UTI are at risk for grade 3-5 VUR and thus should undergo a voiding cystourethrography (VCUG) if their renal ultrasound is abnormal or if they have Pseudomonas UTI. Avoiding VCUG can be considered in afebrile infants and in infants with BNP < 53% or NLR < 1.65.

Nationwide epidemiology of early-onset sepsis in Israel 2010-2015, time to re-evaluate empiric treatment.

AIM: Early-onset neonatal sepsis (EOS) may lead to significant morbidity and mortality, yet the recommended antimicrobials have not changed for many years. We aimed to optimise EOS treatment by examining EOS pathogens, resistance rates and resistance risk factors. METHODS: A retrospective, nationwide cohort study analysing 2010-2015 EOS data in Israel. RESULTS: The 21 participating centres constitute 92% of the total birth cohort (around 180 000 live births/year). Of 549 EOS neonates (0.57/1000 live births), 306 (56%) and 243 (44%) were full-term and preterm, respectively (0.35 vs. 2.94 per/1000 live births). Gram-negative pathogens predominated, especially in preterms. Escherichia coli and Streptococcus agalactiae were most common pathogens (0.2 and 0.19 per 1000 live births, respectively). In 277 Gram-negatives, 16%, 14%, 8% and 3% were gentamicin-resistant, extended-spectrum beta-lactamase (ESBL)-positive, gentamicin-resistant and ESBL-positive, and amikacin-resistant, respectively; preterms had higher resistance rates. No risk factors for antimicrobial resistance were identified. Mortality was reported in 21% of Gram-negative EOS versus 7% of Gram-positive EOS [OR 3.4 (95% CI 1.8-6.2), p < 0.01]. CONCLUSION: In this nationwide study, EOS was caused predominantly by Gram-negatives, with high gentamicin resistance and ESBL phenotype rates, without identifiable resistance risk factors. As EOS is life-threatening, modification of empiric therapy for amikacin-based regimens should be considered, mainly in preterms.

Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012-2013.

Background: Influenza vaccination aims to prevent infection by influenza virus and reduce associated morbidity and mortality; however, vaccine effectiveness (VE) can be modest, especially for subtype A(H3N2). Low VE has been attributed to mismatches between the vaccine and circulating influenza strains and to the vaccine's elicitation of protective immunity in only a subset of the population. The low H3N2 VE in the 2012-2013 season was attributed to egg-adaptive mutations that created antigenic mismatch between the actual vaccine strain (IVR-165) and both the intended vaccine strain (A/Victoria/361/2011) and the predominant circulating strains (clades 3C.2 and 3C.3). Methods: We investigated the basis of low VE in 2012-2013 by determining whether vaccinated and unvaccinated individuals were infected by different viral strains and by assessing the serologic responses to IVR-165, A/Victoria/361/2011, and 3C.2 and 3C.3 strains in an adult cohort before and after vaccination. Results: We found no significant genetic differences between the strains that infected vaccinated and unvaccinated individuals. Vaccination increased titers to A/Victoria/361/2011 and 3C.2 and 3C.3 representative strains as much as to IVR-165. These results are consistent with the hypothesis that vaccination boosted cross-reactive immune responses instead of specific responses against unique vaccine epitopes. Only approximately one-third of the cohort achieved a ≥4-fold increase in titer. Conclusions: In contrast to analyses based on ferret studies, low H3N2 VE in 2012-2013 in adults does not appear to be due to egg adaptation of the vaccine strain. Instead, low VE might have been caused by low vaccine immunogenicity in a subset of the population.

[THE EPIDEMIOLOGY OF CLOSTRIDIUM DIFFICILE INFECTIONS AND ASPECTS PERTAINING TO TREATMENT WITH VANCOMYCIN AT ASSAF HAROFEH MEDICAL CENTER].

BACKGROUND: The epidemiology of Clostridium difficile infections (CDI) have evolved dramatically in the past decade. Vancomycin is the treatment of choice for moderate to severe CDI. However, controlled comparative data pertaining to mild CDI is lacking. Furthermore, the potential impact of vancomycin treatment on subsequent vancomycin-resistant Enterococcus (VRE) isolation remains unknown. METHODS: A retrospective cohort analysis was executed at the Assaf Harofeh Medical Center, from 2013 to 2015. Adult patients (>18 years) with a first episode of acute CDI, determined per pre-established criteria, were enrolled. The efficacy of vancomycin vs. metronidazole among patients with mild CDI, and the independent association of oral vancomycin treatment during the acute CDI and later (up to 18 months) VRE isolation, was analyzed by logistic regression. RESULTS: A total of 260 patients with CDI were enrolled. The majority were elderly (75%), and 56% had moderate to severe disease. Among 75 patients with mild disease, no differences were observed in terms of clinical outcomes between vancomycin or metronidazole treatment. Metronidazole remained non-inferior even after incorporating a prediction score to control for confounders associated with being a "vancomycin case". In multivariable analysis, oral vancomycin treatment during the acute CDI was the strongest independent predictor for later isolation of VRE (aOR=74, p=0.004). CONCLUSIONS: Our study suggests that metronidazole should remain the recommended treatment of choice for mild CDI, due to clinical non-inferiority and an apparent association between vancomycin therapy and subsequent VRE isolation on an individual patient level analysis.

Editorial: Making Fecal Microbiota Transplantation Easier to Swallow: Freeze-Dried Preparation for Recurrent Clostridium difficile Infections.

Fecal microbiota transplant (FMT) has emerged as an effective and increasingly popular therapy for recurrent Clostridium difficile infections in patients that have failed standard antimicrobial treatment. Patient access to FMT is hampered by the logistics of manufacturing, storing, and delivering the inocula. An observational study describes the development and clinical efficacy of freeze-dried FMT capsules for oral administration. While awaiting the emergence of defined bacterial therapeutics for Clostridium difficile infections, this refinement of FMT is an encouraging step toward simplifying FMT treatment. Randomized controlled trials are required to further establish the efficacy and safety of lyophilized FMT.

Shivering in Febrile Children: Frequency and Usefulness in Predicting Serious Bacterial Infections - A Prospective Case-Control Study.

A prospective case-control study was conducted in a pediatric emergency department to describe the proportion of febrile children experiencing shivering and its clinical significance. Shivering was reported in 186 of 645 febrile children (28.8%). The rate of serious bacterial infection was similar in 86 children with shivering and 86 matched controls.

Antibiotic Use in Children - A Cross-National Analysis of 6 Countries.

OBJECTIVES: To describe the rates of pediatric antibiotic use across 6 countries on 3 continents. STUDY DESIGN: Cross-national analysis of 7 pediatric cohorts in 6 countries (Germany, Italy, South Korea, Norway, Spain, and the US) was performed for 2008-2012. Antibiotic dispensings were identified and grouped into subclasses. We calculated the rates of antimicrobial prescriptions per person-year specific to each age group, comparing the rates across different countries. RESULTS: A total of 74 744 302 person-years from all participating centers were included in this analysis. Infants in South Korea had the highest rate of antimicrobial consumption, with 3.41 prescribed courses per child-year during the first 2 years of life. This compares with 1.6 in Lazio, Italy; 1.4 in Pedianet, Italy; 1.5 in Spain; 1.1 in the US; 1.0 in Germany; and 0.5 courses per child-year in Norway. Of antimicrobial prescriptions written in Norway, 64.8% were for first-line penicillins, compared with 38.2% in Germany, 31.8% in the US, 27.7% in Spain, 25.1% in the Italian Pedianet population, 9.8% in South Korea, and 8% in the Italian Lazio population. CONCLUSIONS: We found substantial differences of up to 7.5-fold in pediatric antimicrobial use across several industrialized countries from Europe, Asia, and North America. These data reinforce the need to develop strategies to decrease the unnecessary use of antimicrobial agents.