The impact of paediatric antimicrobial stewardship programmes on patient outcomes.

PURPOSE OF REVIEW: Although there has been an unprecedented global effort to reduce the spread of antimicrobial resistance, little emphasis has been placed on children. This review aims to evaluate the impact of paediatric antimicrobial stewardship programmes as well as providing a practical approach for effectively implementing them in community-based settings and in hospitals. RECENT FINDINGS: Although rates of serious bacterial infection are low in children, the rates of antimicrobial use and resistance are comparable with adults. Different strategies are required to implement antimicrobial stewardship in community-based settings compared to in hospitals. Nationally coordinated, whole-system approaches have achieved long-term, sustainable reductions in antimicrobial prescribing, as well as reductions in resistance rates at population level, with no evidence of an increase in rate of serious infection or bacterial complications. SUMMARY: Antimicrobial stewardship programmes in neonates and children have unique characteristics and issues. There is currently no consensus on how to measure consumption of antimicrobials in neonates and children. This is a research priority. Benchmarking and clinical networks in neonates and paediatrics are important to share practice and drive best use of antimicrobials.

Decolonization and decontamination: what's their role in infection control?

PURPOSE OF REVIEW: Hospital-acquired infections cause up to 19% of infections in paediatric patients contributing to the spread of antimicrobial resistance. This review evaluates the effect of decolonization and decontamination in hospitalized children and neonates as an adjunct to standard infection control measures. RECENT FINDINGS: Few studies on decolonization and decontamination are available in children. The evidence about the effectiveness of daily chlorhexidine washcloths on bacteraemia in paediatric patients relies on a single randomized controlled trial, in neonates with central venous access in a single retrospective observational study. It is uncertain whether nasal mupirocin reduces methicillin-resistant Staphylococcus aureus carriage and infections in neonates, whereas oral chlorhexidine mouthwashes have not proven effective in children in intensive care settings. Scanty evidence demonstrates a reduction in the rate of ventilation-acquired pneumonia with digestive tract decontamination in paediatric patients and no studies are available in neonates. These strategies have not been extensively tested in resource-poor countries. SUMMARY: Strong evidence about the efficacy of decolonization and decontamination interventions exists in adult medicine but not in paediatric patients. There is an urgent need to understand how these interventions could be adapted to neonates and resource-poor settings in which the prevalence of hospital-acquired infections is higher.

Characteristics and outcomes of human parechovirus infection in infants (2008-2012).

UNLABELLED: Human parechoviruses (HPeVs) cause a spectrum of disease ranging from self-limiting illness to severe disease and, sometimes, death. We describe the clinical characteristics and outcomes of HPeV infection in infants. The study describes the clinical and laboratory characteristics and outcomes of infants with HPeV infection during 2008-2012, from three paediatric hospitals in London each with a paediatric intensive care unit. The infants were retrospectively identified through laboratory and patient discharge databases and diagnosed through HPeV PCR. Fifty infants were identified. Half required admission to PICU. Infants less than 3 months were more likely to require PICU (16/25: p < 0.01). Clinical signs at presentation were often indistinguishable from those of bacterial sepsis and meningitis, but inflammatory markers were nearly always (95 % of cases) within normal ranges. Brain MRI showed white matter changes in 10/12 infants. Three of 19 infants with follow-up data (16 %) had significant neurological sequelae. CONCLUSION: HPeV may cause severe disease and long-term neurological sequelae in young infants. HPeV should be considered in infants with clinical features of sepsis/meningitis with normal CSF microscopy. Prospective observational studies are warranted to better define the epidemiology of infection and thus inform future treatment trials.

Effect of women's groups and volunteer peer counselling on rates of mortality, morbidity, and health behaviours in mothers and children in rural Malawi (MaiMwana): a factorial, cluster-randomised controlled trial.

BACKGROUND: Women's groups and health education by peer counsellors can improve the health of mothers and children. We assessed their effects on mortality and breastfeeding rates in rural Malawi. METHODS: We did a 2×2 factorial, cluster-randomised trial in 185,888 people in Mchinji district. 48 equal-sized clusters were randomly allocated to four groups with a computer-generated number sequence. 24 facilitators guided groups through a community action cycle to tackle maternal and child health problems. 72 trained volunteer peer counsellors made home visits at five timepoints during pregnancy and after birth to support breastfeeding and infant care. Primary outcomes for the women's group intervention were maternal, perinatal, neonatal, and infant mortality rates (MMR, PMR, NMR, and IMR, respectively); and for the peer counselling were IMR and exclusive breastfeeding (EBF) rates. Analysis was by intention to treat. The trial is registered as ISRCTN06477126. FINDINGS: We monitored outcomes of 26,262 births between 2005 and 2009. In a factorial model adjusted only for clustering and the volunteer peer counselling intervention, in women's group areas, for years 2 and 3, we noted non-significant decreases in NMR (odds ratio 0.93, 0.64-1.35) and MMR (0.54, 0.28-1.04). After adjustment for parity, socioeconomic quintile, and baseline measures, effects were larger for NMR (0.85, 0.59-1.22) and MMR (0.48, 0.26-0.91). Because of the interaction between the two interventions, a stratified analysis was done. For women's groups, in adjusted analyses, MMR fell by 74% (0.26, 0.10-0.70), and NMR by 41% (0.59, 0.40-0.86) in areas with no peer counsellors, but there was no effect in areas with counsellors (1.09, 0.40-2.98, and 1.38, 0.75-2.54). Factorial analysis for the peer counselling intervention for years 1-3 showed a fall in IMR of 18% (0.82, 0.67-1.00) and an improvement in EBF rates (2.42, 1.48-3.96). The results of the stratified, adjusted analysis showed a 36% reduction in IMR (0.64, 0.48-0.85) but no effect on EBF (1.18, 0.63-2.25) in areas without women's groups, and in areas with women's groups there was no effect on IMR (1.05, 0.82-1.36) and an increase in EBF (5.02, 2.67-9.44). The cost of women's groups was US$114 per year of life lost (YLL) averted and that of peer counsellors was $33 per YLL averted, using stratified data from single intervention comparisons. INTERPRETATION: Community mobilisation through women's groups and volunteer peer counsellor health education are methods to improve maternal and child health outcomes in poor rural populations in Africa. FUNDING: Saving Newborn Lives, UK Department for International Development, and Wellcome Trust.

Neonatal severe bacterial infection impairment estimates in South Asia, sub-Saharan Africa, and Latin America for 2010.

BACKGROUND: Survivors of neonatal infections are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified and yet important for program priority setting. Systematic reviews and meta-analyses were undertaken and applied in a three-step compartmental model to estimate NDI cases after severe neonatal bacterial infection in South Asia, sub-Saharan Africa, and Latin America in neonates of >32 wk gestation (or >1,500 g). METHODS: We estimated cases of sepsis, meningitis, pneumonia, or no severe bacterial infection from among estimated cases of possible severe bacterial infection ((pSBI) step 1). We applied respective case fatality risks ((CFRs) step 2) and the NDI risk among survivors (step 3). For neonatal tetanus, incidence estimates were based on the estimated deaths, CFRs, and risk of subsequent NDI. RESULTS: For 2010, we estimated 1.7 million (uncertainty range: 1.1-2.4 million) cases of neonatal sepsis, 200,000 (21,000-350,000) cases of meningitis, 510,000 cases (150,000-930,000) of pneumonia, and 79,000 cases (70,000-930,000) of tetanus in neonates >32 wk gestation (or >1,500 g). Among the survivors, we estimated moderate to severe NDI after neonatal meningitis in 23% (95% confidence interval: 19-26%) of survivors, 18,000 (2,700-35,000) cases, and after neonatal tetanus in 16% (6-27%), 4,700 cases (1,700-8,900). CONCLUSION: Data are lacking for impairment after neonatal sepsis and pneumonia, especially among those of >32 wk gestation. Improved recognition and treatment of pSBI will reduce neonatal mortality. Lack of follow-up data for survivors of severe bacterial infections, particularly sepsis, was striking. Given the high incidence of sepsis, even minor NDI would be of major public health importance. Prevention of neonatal infection, improved case management, and support for children with NDI are all important strategies, currently receiving limited policy attention.

Pediatric Antifungal Prescribing Patterns Identify Significant Opportunities to Rationalize Antifungal Use in Children.

OBJECTIVE: The need for pediatric antifungal stewardship programs has been driven by an increasing consumption of antifungals for prophylactic and empirical use. Drivers and rational of antifungal prescribing need to be identified to optimize prescription behaviors. METHODS: A prospective modified weekly Point Prevalence Survey capturing antifungal prescriptions for children (> 90 days to < 18 years of age) in 12 centers in England during 26 consecutive weeks was performed. Demographic, diagnostic and treatment information was collected for each patient. Data were entered into an online REDCap database. RESULTS: One thousand two hundred fifty-eight prescriptions were included for 656 pediatric patients, 44.9% were girls, with a median age of 6.4 years (interquartile range, 2.5-11.3). Most common underlying condition was malignancy (55.5%). Four hundred nineteen (63.9%) received antifungals for prophylaxis, and 237 (36.1%) for treatment. Among patients receiving antifungal prophylaxis, 40.2% did not belong to a high-risk group. In those receiving antifungal treatment, 45.9%, 29.4%, 5.1% and 19.6% had a diagnosis of suspected, possible, probable of proven invasive fungal disease (IFD), respectively. Proven IFD was diagnosed in 78 patients, 84.6% (n = 66) suffered from invasive candidiasis and 15.4% (n = 12) from an invasive mold infection. Liposomal amphotericin B was the most commonly prescribed antifungal for both prophylaxis (36.6%) and empiric and preemptive treatment (47.9%). Throughout the duration of the study, 72 (11.0%) patients received combination antifungal therapy. CONCLUSIONS: Antifungal use in pediatric patients is dominated by liposomal amphotericin B and often without evidence for the presence of IFD. A significant proportion of prophylactic and empiric antifungal use was seen in pediatric patients not at high-risk for IFD.

Invasive group A streptococcal disease in pregnant women and young children: a systematic review and meta-analysis.

BACKGROUND: The incidence of invasive disease caused by group A streptococcus (GAS) has increased in multiple countries in the past 15 years. However, despite these reports, to the best of our knowledge, no systematic reviews and combined estimates of the incidence of invasive GAS have been done in key high-risk groups. To address this, we estimated the incidence of invasive GAS disease, including death and disability outcomes, among two high-risk groups-namely, pregnant women and children younger than 5 years. METHODS: We did a systematic review and meta-analyses on invasive GAS outcomes, including incidence, case fatality risks, and neurodevelopmental impairment risk, among pregnant women, neonates (younger than 28 days), infants (younger than 1 year), and children (younger than 5 years) worldwide and by income region. We searched several databases for articles published from Jan 1, 2000, to June 3, 2020, for publications that reported invasive GAS outcomes, and we sought unpublished data from an investigator group of collaborators. We included studies with data on invasive GAS cases, defined as laboratory isolation of Streptococcus pyogenes from any normally sterile site, or isolation of S pyogenes from a non-sterile site in a patient with necrotising fasciitis or streptococcal toxic shock syndrome. For inclusion in pooled incidence estimates, studies had to report a population denominator, and for inclusion in pooled estimates of case fatality risk, studies had to report aggregate data on the outcome of interest and the total number of cases included as a denominator. We excluded studies focusing on groups at very high risk (eg, only preterm infants). We assessed heterogeneity with I2. FINDINGS: Of the 950 published articles and 29 unpublished datasets identified, 20 studies (seven unpublished; 3829 cases of invasive GAS) from 12 countries provided sufficient data to be included in pooled estimates of outcomes. We did not identify studies reporting invasive GAS incidence among pregnant women in low-income and middle-income countries (LMICs) nor any reporting neurodevelopmental impairment after invasive GAS in LMICs. In nine studies from high-income countries (HICs) that reported invasive GAS in pregnancy and the post-partum period, invasive GAS incidence was 0·12 per 1000 livebirths (95% CI 0·11 to 0·14; I2=100%). Invasive GAS incidence was 0·04 per 1000 livebirths (0·03 to 0·05; I2=100%; 11 studies) for neonates, 0·13 per 1000 livebirths (0·10 to 0·16; I2=100%; ten studies) for infants, and 0·09 per 1000 person-years (95% CI 0·07 to 0·10; I2=100%; nine studies) for children worldwide; 0·12 per 1000 livebirths (95% CI 0·00 to 0·24; I2=100%; three studies) in neonates, 0·33 per 1000 livebirths (-0·22 to 0·88; I2=100%; two studies) in infants, and 0·22 per 1000 person-years (0·13 to 0·31; I2=100%; two studies) in children in LMICs; and 0·02 per 1000 livebirths (0·00 to 0·03; I2=100%; eight studies) in neonates, 0·08 per 1000 livebirths (0·05 to 0·11; I2=100%; eight studies) in infants, and 0·05 per 1000 person-years (0·03 to 0·06; I2=100%; seven studies) in children for HICs. Case fatality risks were high, particularly among neonates in LMICs (61% [95% CI 33 to 89]; I2=54%; two studies). INTERPRETATION: We found a substantial burden of invasive GAS among young children. In LMICs, little data were available for neonates and children and no data were available for pregnant women. Incidences of invasive GAS are likely to be underestimates, particularly in LMICs, due to low GAS surveillance. It is essential to improve available data to inform development of prevention and management strategies for invasive GAS. FUNDING: Wellcome Trust.

Adaptation of a probabilistic method (InterVA) of verbal autopsy to improve the interpretation of cause of stillbirth and neonatal death in Malawi, Nepal, and Zimbabwe.

BACKGROUND: Verbal autopsy (VA) is a widely used method for analyzing cause of death in absence of vital registration systems. We adapted the InterVA method to extrapolate causes of death for stillbirths and neonatal deaths from verbal autopsy questionnaires, using data from Malawi, Zimbabwe, and Nepal. METHODS: We obtained 734 stillbirth and neonatal VAs from recent community studies in rural areas: 169 from Malawi, 385 from Nepal, and 180 from Zimbabwe. Initial refinement of the InterVA model was based on 100 physician-reviewed VAs from Malawi. InterVA indicators and matrix probabilities for cause of death were reviewed for clinical and epidemiological coherence by a pediatrician-researcher and an epidemiologist involved in the development of InterVA. The modified InterVA model was evaluated by comparing population-level cause-specific mortality fractions and individual agreement from two methods of interpretation (physician review and InterVA) for a further 69 VAs from Malawi, 385 from Nepal, and 180 from Zimbabwe. RESULTS: Case-by-case agreement between InterVA and reviewing physician diagnoses for 69 cases from Malawi, 180 cases from Zimbabwe, and 385 cases from Nepal were 83% (kappa 0.76 (0.75 - 0.80)), 71% (kappa 0.41(0.32-0.51)), and 74% (kappa 0.63 (0.60-0.63)), respectively. The proportion of stillbirths identified as fresh or macerated by the different methods of VA interpretation was similar in all three settings. Comparing across countries, the modified InterVA method found that proportions of preterm births and deaths due to infection were higher in Zimbabwe (44%) than in Malawi (28%) or Nepal (20%). CONCLUSION: The modified InterVA method provides plausible results for stillbirths and newborn deaths, broadly comparable to physician review but with the advantage of internal consistency. The method allows standardized cross-country comparisons and eliminates the inconsistencies of physician review in such comparisons.

Listeria infection in young infants: results from a national surveillance study in the UK and Ireland.

OBJECTIVES: To describe the epidemiology, age at infection, clinical characteristics and outcome of listeria infection in young infants to inform management and empiric antibiotic choice in young infants. DESIGN: Prospective 2-year surveillance of Listeria monocytogenes infection in young infants detected through the British Paediatric Surveillance Unit 'orange card' system and triangulated with the public health laboratories. SETTING: National population study (England, Wales, Scotland and the Ireland) PATIENTS: All infants under 90 days with proven or probable invasive listeriosis MAIN OUTCOME MEASURES: Incidence, mortality, age of infection, clinical characteristics and outcome RESULTS: During a 2-year period (2017-2019), 27 cases of listeriosis in infants <90 days of age were reported. The incidence of listeriosis in this study was 1.8 per 100 000 live births with 7% mortality (2/27). Nearly all cases presented within the first 24 hours of life (26/27). The majority (20/27, 74%) were born preterm and 16/24 (67%) were born to women from ethnic minority backgrounds. CONCLUSIONS: Invasive listeriosis in young infants in the UK and Ireland is rare and presents early in the neonatal period. National guidelines that recommend the use of amoxicillin as part of empiric regimes for sepsis and meningitis in infants over 1 month of age should be modified.

A Survey on National Pediatric Antibiotic Stewardship Programs, Networks and Guidelines in 23 European Countries.

BACKGROUND: Misuse, overuse of antimicrobials and increasing rates of antimicrobial resistance are well-recognized problems throughout Europe. The aim of this survey was to describe the current pediatric antibiotic stewardship (PAS) landscape across Europe and identify gaps, in terms of national programs, networks and guidelines. METHODS: A survey of 17 questions was circulated in July 2019 among 24 European pediatric infectious disease researchers and clinicians, professors and heads of department on the existence of PAS programs, national networks and meetings, established competencies, metrics and guidelines. RESULTS: We received responses from 23 countries. National guidelines on the management of children with common infections treated in hospital settings exist in 15 of 23 (70%); only 8 of 15 (53%) had been updated within the previous 4 years. Most provide guidance on antibiotic initiation and duration (14 of 15, 93%), but few on when to transition from intravenous to oral antibiotics (7 of 15, 47%). National PAS competencies have only been developed in 4 countries; only 1 addressed both community and hospital prescribing. Organized national PAS networks are only established in the United Kingdom and Germany; 21 of 23, 91% countries had no agreed metric for antibiotic prescribing in children; 2 of 23 were based on daily defined doses. CONCLUSIONS: Fragmented implementation of PAS programs, no agreed metrics, lack of established PAS competencies and national PAS networks along with inexistent funding is alarming in view of existing high rates of antimicrobial resistance in Europe.

Neonatal Antifungal Consumption Is Dominated by Prophylactic Use; Outcomes From The Pediatric Antifungal Stewardship: Optimizing Antifungal Prescription Study.

BACKGROUND: Diagnostic challenges combined with the vulnerability of neonates to develop invasive candidiasis (IC) may lead to antifungal administration in the absence of IC. A modified point-prevalence study was performed to obtain an improved insight and understanding of antifungal prescribing in this specific patient population. METHODS: Neonates and infants ≤90 days of age receiving systemic antifungals from 12 centers in England were included. Data were collected prospectively during 26 consecutive weeks and entered into an online REDCap database. RESULTS: Two hundred eighty neonates and infants were included, the majority ≤1 month of age (68.2%). Prematurity was the commonest underlying condition (68.9%). Antifungals were prescribed for prophylactic reason in 79.6%; of those, 64.6% and 76.3% were extreme low birth weight infants and prematurely born neonates, respectively. Additional risk factors were present in almost all patients, but only 44.7% had ≥3 risk factors rendering them more susceptible to develop IC. Nonpremature and non extremely low birth weight premature infants only scored ≥3 risk factors in 32.6% and 15%, respectively. Fluconazole was the most common antifungal used (76.7% of all prescriptions), and commonly underdosed as treatment. The number of microbiologic proven IC was low, 5.4%. CONCLUSIONS: Neonatal antifungal prophylaxis is commonly prescribed outside the recommendations based on known risk profiles. Fluconazole is the main antifungal prescribed in neonates and infants, with underdosing frequently observed when prescribed for treatment. Number of proven IC was very low. These observations should be taken into consideration to develop a national pediatric Antifungal Stewardship program aiming to guide rational prescribing.

Women's groups' perceptions of maternal health issues in rural Malawi.

BACKGROUND: Improvements in preventive and care-seeking behaviours to reduce maternal mortality in rural Africa depend on the knowledge and attitudes of women and communities. Surveys have indicated a poor awareness of maternal health problems by individual women. We report the perceptions of women's groups to such issues in the rural Mchinji district of Malawi. METHODS: Participatory women's groups in the Mchinji district identified maternal health problems (172 groups, 3171 women) and prioritised problems they considered most important (171 groups, 2833 women). In-depth qualitative data was obtained through six focus-group discussions with the women's groups, three with women's group facilitators, and four interviews with facilitator supervisors. FINDINGS: The maternal health problems most commonly identified by more than half the groups were anaemia (87%), malaria (80%), retained placenta (77%), obstructed labour (76%), malpresentation (71%), antepartum and postpartum haemorrhage (70% each), and pre-eclampsia (56%). The five problems prioritised as most important were anaemia (sum of rank score 304), malpresentation (295), retained placenta (277), obstructed labour (276). and postpartum haemorrhage (275). HIV/AIDS and sepsis were identified or prioritised much less because complexity and contextual factors hindered their consideration. INTERPRETATION: Rural Malawian women meeting in participatory groups showed a developed awareness of maternal health problems and the concern and motivation to address them. Community mobilisation strategies, such as women's groups, might be effective at reducing maternal mortality because they can draw on the collective capacity in communities to solve problems and make women's voices heard by decision-makers.

Serious bacterial infections in neonates: improving reporting and case definitions.

Neonatal infections affect about 7 million neonates causing over 600 000 deaths every year. Estimating the burden is challenging as there are multiple reporting criteria and definitions for serious bacterial infections in neonates. Essential criteria for reporting serious neonatal bacterial infections have recently been published as the STROBE-NI checklist and, in the context of maternal vaccination, definitions have been published by the Brighton Collaboration Global Alignment of Immunization safety Assessment in pregnancy (GAIA) project. Standardisation of reporting criteria is essential to allow data comparability. This an important step in providing a clearer picture of the burden of serious bacterial infections in neonates and a welcome progress for guiding new investments in interventions.

Neonatal listeriosis in the UK 2004-2014.

OBJECTIVE: To define the clinical features and outcomes of neonatal listeriosis, and identify the maternal risk factors to seek scope for improvement. METHODS: Neonatal listeriosis was identified prospectively from a United Kingdom neonatal infection surveillance network (neonIN) between 2004 and 2014. The participating neonatal units completed a study-specific proforma. RESULTS: The incidence of neonatal listeriosis was 3.4 per 100,000 live births. Of the 21 cases identified, 19 were confirmed with a median gestational age of 33 weeks and a median birth weight of 1960 g. The majority had clinical features (95%, 18/19), presented within the first 24 h (95%, 18/19), and received penicillin empirically (94%, 18/19). The neonatal case-fatality rate was 21% (24% if probable cases were included). A proportion of mothers were investigated (60%, 12/18) and diagnosed with listeriosis (58%, 7/12); 32% (6/19) were treated with antibiotics but only 33% (6/12) included penicillin. DISCUSSION: Despite its rarity and the prompt and appropriate use of antibiotics neonatal listeriosis has a high case-fatality rate. There is room for improvement in the adherence to the empiric antibiotic choice for puerperal sepsis, according to the national guidelines as this, would target listeriosis. Strategies should be in place to prevent pregnancy-associated listeriosis in higher risk population.

Guidance for the collection of case report form variables to assess safety in clinical trials of vaccines in pregnancy.

Vaccination in pregnancy is an effective strategy to prevent serious infections in mothers and their infants. Safety of this strategy is of principal importance to all stakeholders. As the number of studies assessing safety of vaccines in pregnancy increases, the need to ensure consistent collection and reporting of critical data to allow comparisons and data pooling becomes more important. The Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project aims to improve data collection and create a shared understanding of maternal, fetal and neonatal outcomes in order to progress the global agenda for vaccination in pregnancy. The guidance in this document has been developed to harmonize the data collected in case report forms used for safety monitoring in clinical trials of vaccination in pregnant women. Data to be collected is prioritized to allow applicability in diverse research settings, including low and middle-income countries. Standardized data will enable the research community to have a common base upon which to conduct meta-analyses, strengthening the applicability of outcomes to different settings.

Using a simple point-prevalence survey to define appropriate antibiotic prescribing in hospitalised children across the UK.

BACKGROUND: The National Health Service England, Commissioning for Quality and Innovation for Antimicrobial Resistance (CQUIN AMR) aims to reduce the total antibiotic consumption and the use of certain broad-spectrum antibiotics in secondary care. However, robust baseline antibiotic use data are lacking for hospitalised children. In this study, we aim to describe, compare and explain the prescription patterns of antibiotics within and between paediatric units in the UK and to provide a baseline for antibiotic prescribing for future improvement using CQUIN AMR guidance. METHODS: We conducted a cross-sectional study using a point prevalence survey (PPS) in 61 paediatric units across the UK. The standardised study protocol from the Antibiotic Resistance and Prescribing in European Children (ARPEC) project was used. All inpatients under 18 years of age present in the participating hospital on the day of the study were included except neonates. RESULTS: A total of 1247 (40.9%) of 3047 children hospitalised on the day of the PPS were on antibiotics. The proportion of children receiving antibiotics showed a wide variation between both district general and tertiary hospitals, with 36.4% ( 95% CI 33.4% to 39.4%) and 43.0% (95% CI 40.9% to 45.1%) of children prescribed antibiotics, respectively. About a quarter of children on antibiotic therapy received either a medical or surgical prophylaxis with parenteral administration being the main prescribed route for antibiotics (>60% of the prescriptions for both types of hospitals). General paediatrics units were surprisingly high prescribers of critical broad-spectrum antibiotics, that is, carbapenems and piperacillin-tazobactam. CONCLUSIONS: We provide a robust baseline for antibiotic prescribing in hospitalised children in relation to current national stewardship efforts in the UK. Repeated PPS with further linkage to resistance data needs to be part of the antibiotic stewardship strategy to tackle the issue of suboptimal antibiotic use in hospitalised children.

Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE-NI): an extension of the STROBE statement for neonatal infection research.

Neonatal infections are estimated to account for a quarter of the 2·8 million annual neonatal deaths, as well as approximately 3% of all disability-adjusted life-years. Despite this burden, few data are available on incidence, aetiology, and outcomes, particularly regarding impairment. We aimed to develop guidelines for improved scientific reporting of observational neonatal infection studies, to increase comparability and to strengthen research in this area. This checklist, Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE- NI), is an extension of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement. STROBE-NI was developed following systematic reviews of published literature (1996-2015), compilation of more than 130 potential reporting recommendations, and circulation of a survey to relevant professionals worldwide, eliciting responses from 147 professionals from 37 countries. An international consensus meeting of 18 participants (with expertise in infectious diseases, neonatology, microbiology, epidemiology, and statistics) identified priority recommendations for reporting, additional to the STROBE statement. Implementation of these STROBE-NI recommendations, and linked checklist, aims to improve scientific reporting of neonatal infection studies, increasing data utility and allowing meta-analyses and pathogen-specific burden estimates to inform global policy and new interventions, including maternal vaccines.

Neonatal infections: Case definition and guidelines for data collection, analysis, and presentation of immunisation safety data.

Maternal vaccination is an important area of research and requires appropriate and internationally comparable definitions and safety standards. The GAIA group, part of the Brighton Collaboration was created with the mandate of proposing standardised definitions applicable to maternal vaccine research. This study proposes international definitions for neonatal infections. The neonatal infections GAIA working group performed a literature review using Medline, EMBASE and the Cochrane collaboration and collected definitions in use in neonatal and public health networks. The common criteria derived from the extensive search formed the basis for a consensus process that resulted in three separate definitions for neonatal blood stream infections (BSI), meningitis and lower respiratory tract infections (LRTI). For each definition three levels of evidence are proposed to ensure the applicability of the definitions to different settings. Recommendations about data collection, analysis and presentation are presented and harmonized with the Brighton Collaboration and GAIA format and other existing international standards for study reporting.

The current and future roles of neonatal infection surveillance programmes in combating antimicrobial resistance.

Neonatal sepsis is an important cause of morbidity and mortality, particularly in premature or low birth weight babies. Hospital-acquired blood stream infections represent a significant and largely preventable cause of disease in this population. Neonatal units have been identified as a common site for the development and transmission of antimicrobial-resistant pathogens, a significant issue in modern medicine. Neonatal surveillance programmes collect prospective data on infection rates and may be used to optimise therapy, benchmark practice and develop quality improvement programmes. Despite this, the number of networks is relatively few and these are largely concentrated in resource-rich nations. Furthermore, surveillance definitions may vary between programmes impairing our ability to draw comparisons between them. Better harmonisation is required between networks to ensure that they achieve their potential as a valuable tool for benchmarking of hospital-acquired infection rates between units.