Identifying AWaRe indicators for appropriate antibiotic use: a narrative review.

Introduction: Quality indicators (QIs) are widely used tools for antibiotic stewardship programmes. The Access, Watch, Reserve (AWaRe) system has been developed by the WHO to classify antibiotics based on their spectrum of activity and potential selection of antibiotic resistance. This review aimed to identify existing indicators for optimal antibiotic use to inform the development of future AWaRe QIs.

Multicentre external validation of the Neonatal Healthcare-associated infectiOn Prediction (NeoHoP) score: a retrospective case-control study.

Background And Objectives: Neonatal mortality due to severe bacterial infections is a pressing global issue, especially in low-middle-income countries (LMICs) with constrained healthcare resources. This study aims to validate the Neonatal Healthcare-associated infectiOn Prediction (NeoHoP) score, designed for LMICs, across diverse neonatal populations.

Methods: Prospective data from three South African neonatal units in the Neonatal Sepsis Observational (NeoOBS) study were analysed.

Determining sample size in a personalized randomized controlled (PRACTical) trial.

In clinical settings with no commonly accepted standard-of-care, multiple treatment regimens are potentially useful, but some treatments may not be appropriate for some patients. A personalized randomized controlled trial (PRACTical) design has been proposed for this setting. For a network of treatments, each patient is randomized only among treatments which are appropriate for them.

The scope of the antimicrobial resistance challenge.

Each year, an estimated 7·7 million deaths are attributed to bacterial infections, of which 4.95 million are associated with drug-resistant pathogens, and 1·27 million are caused by bacterial pathogens resistant to the antibiotics available. Access to effective antibiotics when indicated prolongs life, reduces disability, reduces health-care expenses, and enables access to other life-saving medical innovations.

Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries.

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs.

A systematic review of national interventions and policies to optimize antibiotic use in healthcare settings in England.

Objectives: To identify and assess the effectiveness of national antibiotic optimization interventions in primary and secondary care in England (2013-2022).

Methods: A systematic scoping review was conducted. Literature databases (Embase and Medline) were used to identify interventions and evaluations.

Challenges for global antibiotic regimen planning and establishing antimicrobial resistance targets: implications for the WHO Essential Medicines List and AWaRe antibiotic book dosing.

SUMMARYThe World Health Organisation's 2022 AWaRe Book provides guidance for the use of 39 antibiotics to treat 35 infections in primary healthcare and hospital facilities. We review the evidence underpinning suggested dosing regimens. Few ( = 18) population pharmacokinetic studies exist for key oral AWaRe antibiotics, largely conducted in homogenous and unrepresentative populations hindering robust estimates of drug exposures.

Safety and efficacy of whole-body chlorhexidine gluconate cleansing with or without emollient in hospitalised neonates (NeoCHG): a multicentre, randomised, open-label, factorial pilot trial.

Background: Healthcare-associated infections account for substantial neonatal in-hospital mortality. Chlorhexidine gluconate (CHG) whole body skin application could reduce sepsis by lowering bacterial colonisation density, although safety and optimal application regimen is unclear. Emollients, including sunflower oil, may independently improve skin condition, thereby reducing sepsis.

Incidence, pathogens and antimicrobial resistance of blood and cerebrospinal fluid isolates from a tertiary neonatal unit in South Africa: A 10 year retrospective review.

Objective: To determine trends in incidence, etiology and antimicrobial susceptibility of blood and cerebrospinal fluid (CSF) culture confirmed infections in hospitalized infants in a large tertiary neonatal unit in South Africa.

Methods: Single-center, retrospective review of laboratory records of bacteria and fungi, and their susceptibility profiles, isolated from blood and CSF of infants hospitalized in the neonatal unit at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, from 1st January 2010 to 31st December 2019. Laboratory data on isolates and their antimicrobial susceptibilities were collected.

The Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA): investigating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin pharmacokinetics from birth to adolescence.

Background: Pharmacokinetic (PK) data underlying paediatric penicillin dosing remain limited, especially in critical care.

Objectives: The primary objective of the Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA) was to characterize PK profiles of commonly used penicillins using data obtained during routine care, to further understanding of PK variability and inform future evidence-based dosing.

Methods: NAPPA was a multicentre study of amoxicillin, co-amoxiclav, benzylpenicillin, flucloxacillin and piperacillin/tazobactam.

Early-versus late-onset sepsis in neonates - time to shift the paradigm?

Background: Neonatal sepsis is traditionally classified as early-onset sepsis (EOS) and late-onset sepsis (LOS) disease categories. This paradigm was based on observed epidemiological data from high income settings. However, increasing availability of microbiology results from diverse settings challenges these assumptions, necessitating re-examination of neonatal sepsis classifications.

Harmonization of Amoxicillin Dose, Duration, and Formulation for Acute Childhood Respiratory Infections.

Pediatric guidelines vary in their recommended amoxicillin dosing for common respiratory infections. It would help program delivery if there was harmonization of dosing and formulation of amoxicillin across multiple clinical respiratory infections, considering the pharmacokinetics, common targets, drug resistance, availability, cost effectiveness, and ease of administration. The World Health Organization EML AWaRe Book recommends higher dose amoxicillin given twice daily for five days for all uncomplicated respiratory infections where an antibiotic is indicated.

Antibiotics for lower respiratory tract infection in children presenting in primary care: ARTIC-PC RCT.

Background: Antimicrobial resistance is a global health threat. Antibiotics are commonly prescribed for children with uncomplicated lower respiratory tract infections, but there is little randomised evidence to support the effectiveness of antibiotics in treating these infections, either overall or relating to key clinical subgroups in which antibiotic prescribing is common (chest signs; fever; physician rating of unwell; sputum/rattly chest; shortness of breath).

Objectives: To estimate the clinical effectiveness and cost-effectiveness of amoxicillin for uncomplicated lower respiratory tract infections in children both overall and in clinical subgroups.

Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS).

Background: There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design.

Methods And Findings: Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa).

Cefotaxime/sulbactam plus gentamicin as a potential carbapenem- and amikacin-sparing first-line combination for neonatal sepsis in high ESBL prevalence settings.

Background: Infection with ESBL-producing Enterobacteriaceae infection is ubiquitous in some neonatal ICUs and increasing levels of antibiotic resistance are a cause for urgent concern. Delineation of bacterial and viral sepsis can be challenging, often leading to patients receiving empirical antibiotics without or whilst waiting for a definitive causal diagnosis. Empirical therapy is often dependent on broad-spectrum 'Watch' antibiotics, contributing to further resistance.

Challenges in the Implementation of the NeoOBS Study, a Global Pragmatic Observational Cohort Study, to Investigate the Aetiology and Management of Neonatal Sepsis in the Hospital Setting.

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis.