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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

BackgroundGroup B streptococcus is a leading cause of serious infection in young infants in many countries worldwide. We aimed to define the burden and clinical features of invasive group B streptococcal disease in infants younger than 90 days in the UK and Ireland, together with the characteristics of disease-causing isolates.MethodsProspective, active national surveillance of invasive group B streptococcal disease in infants younger than 90 days was done from April 1, 2014, to April 30, 2015, through the British Paediatric Surveillance Unit, microbiology reference laboratories, and national public health agencies in the UK and Ireland. Early onset was defined as disease in the first 6 days of life and late onset was defined as 7–89 days of life. Incidence was calculated using livebirths in 2014 (after adjustment for the 13-month surveillance period). Isolates were characterised by serotyping, multilocus sequence typing, and antimicrobial susceptibility testing.Findings856 cases of group B streptococcus were identified in 2014–15, an incidence of 0·94 per 1000 livebirths (95% CI 0·88–1·00). Incidence for early-onset disease (n=517) was 0·57 per 1000 livebirths (95% CI 0·52–0·62), and for late-onset disease (n=339) was 0·37 per 1000 livebirths (0·33–0·41). 53 infants died (case fatality rate 6·2%), of whom 27 had early-onset disease (case fatality rate 5·2%) and 26 had late-onset disease (case fatality rate 7·7%). The predominant serotypes were III (241 [60%] of 402 serotyped isolates) and Ia (69 [17%]); five serotypes (Ia, Ib, II, III, V) accounted for 377 (94%) of all serotyped isolates.InterpretationThe incidence of invasive infant group B streptococcal disease in the UK and Ireland has increased since a comparable study done in 2000–01. The burden of early-onset disease has not declined despite the introduction of national prevention guidelines. New strategies for prevention are required.FundingMeningitis Now.

Objective To describe the epidemiology of neonatal infections and of antimicrobial use in Greek Neonatal Units (NNUs) in order to develop national, evidence-based guidelines on empiric antimicrobial use for neonatal sepsis in Greece. Design Retrospective analysis of prospectively collected infection surveillance data from 2012 to 2015, together with a Point Prevalence Survey (PPS) on antimicrobial use and the collection of data on local empiric antimicrobial policies. Setting 16 NNUs in Greece participating in the neonIN infection surveillance network Patients Newborns in participating NNUs who had a positive blood, cerebrospinal fluid or urine culture and were treated with at least 5 days of antibiotics. Results 459 episodes were recorded in 418 infants. The overall incidence of infection was 50/1000 NNU-admissions. The majority of episodes were late-onset sepsis (LOS) (413, 90%). Coagulase-negative Staphylococci (80%) were the most common Gram-positive organisms causing LOS and Klebsiella spp (39%) the most common Gram-negative. Nearly half (45%) of the Klebsiella spp were resistant to at least one aminoglycoside. The PPS revealed that 196 of 484 (40%) neonates were on antimicrobials. The survey revealed wide variation in empiric antimicrobial policies for LOS. Conclusions This is the largest collection of data on the epidemiology of neonatal infections in Greece and on neonatal antimicrobial use. It provides the background for the development of national evidence-based guidelines. Continuous surveillance, the introduction of antimicrobial stewardship interventions and evidence-based guidelines are urgently required. © 2019 Author(s) (or their employer(s)). Re-use permitted under CC BY-NC.

OBJECTIVES: To determine risk factors for GBS colonisation in Gambian mothers and in their infants from birth to day 60-89 of age. METHODS: Swabs and breastmilk from mothers/infant pairs were collected and cultured on selective agar. Negative samples were analysed for GBS DNA via real-time PCR. Positive isolates were serotyped using multiplex PCR and gel-agarose electrophoresis. RESULTS: Seven hundred and fifty women/infant pairs were recruited. 253 women (33.7%) were GBS-colonised at delivery. The predominant serotypes were: V (55%), II (16%), III (10%), Ia (8%) and Ib (8%). 186 infants were colonised (24.8%) at birth, 181 (24.1%) at 6 days and 96 at day 60-89 (14%). Infants born before 34 weeks of gestation and to women with rectovaginal and breastmilk colonisation at delivery had increased odds of GBS colonisation at birth. Season of birth was associated with increased odds of persistent infant GBS colonisation (dry season vs. wet season AOR 2.9; 95% CI 1.6-5.2). CONCLUSION: GBS colonisation is common in Gambian women at delivery and in their infants to day 60-89 and is dominated by serotype V. In addition to maternal colonisation, breastmilk and season of birth are important risk factors for infant GBS colonisation.

Objective: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with increased risk of adverse maternal and perinatal outcomes. Vaccines are highly effective at preventing severe coronavirus disease 2019 (COVID-19), but there are limited data on COVID-19 vaccines in pregnancy. This study aimed to investigate the reactogenicity and immunogenicity of COVID-19 vaccines in pregnant women when administered according to the 12-week-interval dosing schedule recommended in the UK. Methods: this was a cohort study of pregnant women receiving COVID-19 vaccination between April and September 2021. The outcomes were immunogenicity and reactogenicity after COVID-19 vaccination. Pregnant women were recruited by phone, e-mail and/or text and were vaccinated according to vaccine availability at their local vaccination center. For immunogenicity assessment, blood samples were taken at specific timepoints after each dose to evaluate nucleocapsid protein (N) and spike protein (S) antibody titers. The comparator group comprised non-pregnant female healthcare workers in the same age group who were vaccinated as part of the national immunization program in a contemporaneous longitudinal cohort study. Longitudinal changes in serum antibody titers and association with pregnancy status were assessed using a two-step regression approach. Reactogenicity assessment in pregnant women was undertaken using an online questionnaire. The comparator group comprised non-pregnant women aged 18–49 years who had received two vaccine doses in primary care. The association of pregnancy status with reactogenicity was assessed using logistic regression analysis. Results: overall, 67 pregnant women, of whom 66 had received a mRNA vaccine, and 79 non-pregnant women, of whom 50 had received a mRNA vaccine, were included in the immunogenicity study. Most (61.2%) pregnant women received their first vaccine dose in the third trimester, while 3.0% received it in the first trimester and 35.8% in the second trimester. SARS-CoV-2 S-antibody geometric mean concentrations after mRNA vaccination were not significantly different at 2–6 weeks after the first dose but were significantly lower at 2–6 weeks after the second dose in infection-naïve pregnant compared with non-pregnant women. In pregnant women, prior infection was associated with higher antibody levels at 2–6 weeks after the second vaccine dose. Reactogenicity analysis included 108 pregnant women and 116 non-pregnant women. After the first dose, tiredness and chills were reported less commonly in pregnant compared with non-pregnant women (P = 0.043 and P = 0.029, respectively). After the second dose, feeling generally unwell was reported less commonly (P = 0.046) in pregnant compared with non-pregnant women. Conclusions: using an extended 12-week interval between vaccine doses, antibody responses after two doses of mRNA COVID-19 vaccine were found to be lower in pregnant compared with non-pregnant women. Strong antibody responses were achieved after one dose in previously infected women, regardless of pregnancy status. Pregnant women reported fewer adverse events after both the first and second dose of vaccine. These findings should now be addressed in larger controlled studies., NA

Summary Background Vancomycin is the most widely used antibiotic for neonatal Gram-positive sepsis, but clinical outcome data of dosing strategies are scarce. The NeoVanc programme comprised extensive preclinical studies to inform a randomised controlled trial to assess optimised vancomycin dosing. We compared the efficacy of an optimised regimen to a standard regimen in infants with late onset sepsis that was known or suspected to be caused by Gram-positive microorganisms. Methods NeoVanc was an open-label, multicentre, phase 2b, parallel-group, randomised, non-inferiority trial comparing the efficacy and toxicity of an optimised regimen of vancomycin to a standard regimen in infants aged 90 days or younger. Infants with at least three clinical or laboratory sepsis criteria or confirmed Gram-positive sepsis with at least one clinical or laboratory criterion were enrolled from 22 neonatal intensive care units in Greece, Italy, Estonia, Spain, and the UK. Infants were randomly assigned (1:1) to either the optimised regimen (25 mg/kg loading dose, followed by 15 mg/kg every 12 h or 8 h dependent on postmenstrual age, for 5 ± 1 days) or the standard regimen (no loading dose; 15 mg/kg every 24 h, 12 h, or 8 h dependent on postmenstrual age for 10 ± 2 days). Vancomycin was administered intravenously via 60 min infusion. Group allocation was not masked to local investigators or parents. The primary endpoint was success at the test of cure visit (10 ± 1 days after the end of actual vancomycin therapy) in the per-protocol population, where success was defined as the participant being alive at the test of cure visit, having a successful outcome at the end of actual vancomycin therapy, and not having a clinically or microbiologically significant relapse or new infection requiring antistaphylococcal antibiotics for more than 24 h within 10 days of the end of actual vancomycin therapy. The non-inferiority margin was −10%. Safety was assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov ( NCT02790996 ). Findings Between March 3, 2017, and July 29, 2019, 242 infants were randomly assigned to the standard regimen group (n=122) or the optimised regimen group (n=120). Primary outcome data in the per-protocol population were available for 90 infants in the optimised group and 92 in the standard group. 64 (71%) of 90 infants in the optimised group and 73 (79%) of 92 in the standard group had success at test of cure visit; non-inferiority was not confirmed (adjusted risk difference −7% [95% CI −15 to 2]). Incomplete resolution of clinical or laboratory signs after 5 ± 1 days of vancomycin therapy was the main factor contributing to clinical failure in the optimised group. Abnormal hearing test results were recorded in 25 (30%) of 84 infants in the optimised group and 12 (15%) of 79 in the standard group (adjusted risk ratio 1·96 [95% CI 1·07 to 3·59], p=0·030). There were six vancomycin-related adverse events in the optimised group (one serious adverse event) and four in the standard group (two serious adverse events). 11 infants in the intention-to-treat population died (six [6%] of 102 infants in the optimised group and five [5%] of 98 in the standard group). Interpretation In the largest neonatal vancomycin efficacy trial yet conducted, no clear clinical impact of a shorter duration of treatment with a loading dose was demonstrated. The use of the optimised regimen cannot be recommended because a potential hearing safety signal was identified; long-term follow-up is being done. These results emphasise the importance of robust clinical safety assessments of novel antibiotic dosing regimens in infants. Funding EU Seventh Framework Programme for research, technological development and demonstration.

Background: concerns have been raised regarding a potential surge of COVID-19 in pregnancy, secondary to the rising numbers of COVID-19 in the community, easing of societal restrictions, and vaccine hesitancy. Although COVID-19 vaccination is now offered to all pregnant women in the United Kingdom; limited data exist on its uptake and safety. Objective: this study aimed to investigate the uptake and safety of COVID-19 vaccination among pregnant women. Study design: this was a cohort study of pregnant women who gave birth at St George's University Hospitals National Health Service Foundation Trust, London, United Kingdom, between March 1, 2020, and July 4, 2021. The primary outcome was uptake of COVID-19 vaccination and its determinants. The secondary outcomes were perinatal safety outcomes. Data were collected on COVID-19 vaccination uptake, vaccination type, gestational age at vaccination, and maternal characteristics, including age, parity, ethnicity, index of multiple deprivation score, and comorbidities. Further data were collected on perinatal outcomes, including stillbirth (fetal death at ?24 weeks’ gestation), preterm birth, fetal and congenital abnormalities, and intrapartum complications. Pregnancy and neonatal outcomes of women who received the vaccine were compared with that of a matched cohort of women with balanced propensity scores. Effect magnitudes of vaccination on perinatal outcomes were reported as mean differences or odds ratios with 95% confidence intervals. Factors associated with antenatal vaccination were assessed with logistic regression analysis. Results: Data were available for 1328 pregnant women of whom 140 received at least 1 dose of the COVID-19 vaccine before giving birth and 1188 women who did not; 85.7% of those vaccinated received their vaccine in the third trimester of pregnancy and 14.3% in the second trimester of pregnancy. Of those vaccinated, 127 (90.7%) received a messenger RNA vaccine and 13 (9.3%) a viral vector vaccine. There was evidence of reduced vaccine uptake in younger women (P=.001), women with high levels of deprivation (ie, fifth quintile of the index of multiple deprivation; P=.008), and women of Afro-Caribbean or Asian ethnicity compared with women of White ethnicity (P[removed].05 for all): stillbirth (0.0% vs 0.2%), fetal abnormalities (2.2% vs 2.5%), postpartum hemorrhage (9.8% vs 9.0%), cesarean delivery (30.8% vs 34.1%), small for gestational age (12.0% vs 12.8%), maternal high-dependency unit or intensive care admission (6.0% vs 4.0%), or neonatal intensive care unit admission (5.3% vs 5.0%). Intrapartum pyrexia (3.7% vs 1.0%; P=.046) was significantly increased but the borderline statistical significance was lost after excluding women with antenatal COVID-19 infection (P=.079). Mixed-effects Cox regression showed that vaccination was not significantly associated with birth at, NA