Antimicrobial-resistant Gram-negative infections in neonates: burden of disease and challenges in treatment.

PURPOSE OF REVIEW: This review summarizes the main challenges of antimicrobial resistance (AMR) in the neonatal population with a special focus on multidrug-resistant (MDR) Gram-negative pathogens. RECENT FINDINGS: MDR-Gram-negative bacteria are a great concern in the neonatal population, with a worldwide rise in the reported incidence and with very limited therapeutic options. Extended-spectrum β-lactamase and carbapenem-resistant Enterobacteriaceae (CRE) have been reported as responsible for neonatal ICU outbreaks. Hospital data from low/middle-income countries show high proportions of isolates from neonates resistant to the WHO first-line and second-line recommended treatments. The spread of CRE has resulted in old antibiotics, such as colistin and fosfomycin, to be considered as alternative treatment options, despite the paucity of available data on safety and appropriate dosage. SUMMARY: Improved global neonatal AMR surveillance programmes including both epidemiology and clinical outcomes are critical for defining the burden and designing interventions. The optimal empiric treatment for neonatal sepsis in settings of high rates of AMR is currently unknown. Both strategic trials of older antibiotics and regulatory trials of new antibiotics are required to improve clinical outcomes in MDR-Gram-negative neonatal sepsis

Evaluation of existing and desired antimicrobial stewardship activities and strategies in Swiss hospitals.

Antimicrobial stewardship (AMS) is an important component in the fight against antimicrobial resistance. Currently, few hospitals have an ongoing institutional AMS programme. Swissnoso - the national centre for infection prevention - has launched a national Swiss AMS initiative supported by the office of public health. To guide AMS priorities and resources, current AMS activities in Switzerland were assessed. We distributed an internet-based questionnaire directed mainly to board-certified infectious diseases specialists and, if not available, senior internal medicine staff. Responses were received from 63/134 hospitals surveyed. More than 90% were in favour of national treatment guidelines currently in development under the umbrella of the Swiss society for infectious diseases. Many AMS activities - such as antimicrobial formulary restrictions and approval systems, review of antimicrobial prescriptions with point of care intervention, and direct feedback or therapeutic drug monitoring - are currently lacking in the majority of Swiss hospitals surveyed. Development of a modular formal AMS standard for Swiss hospitals may aid in advancing current AMS strategies and in introducing AMS programmes in Switzerland. In combination with the surveillance of antimicrobial use and resistance by ANRESIS, the national antimicrobial resistance surveillance system, this approach may reduce the use of antimicrobial agents and consequently the risk of emergence of multi-resistant pathogens

Association between antimicrobial stewardship programs and antibiotic use globally: a systematic review and meta-analysis

IMPORTANCE: Antimicrobial resistance continues to spread rapidly at a global scale. Little evidence exists on the association of antimicrobial stewardship programs (ASPs) with the consumption of antibiotics across health care and income settings. OBJECTIVE: To synthesize current evidence regarding the association between antimicrobial stewardship programs and the consumption of antibiotics globally. DATA SOURCES: PubMed, Web of Science, and Scopus databases were searched from August 1, 2010, to Aug 1, 2020. Additional studies from the bibliography sections of previous systematic reviews were included. STUDY SELECTION: Original studies of the association of ASPs with antimicrobial consumption across health care and income settings. Animal and environmental studies were excluded. DATA EXTRACTION AND SYNTHESIS: Following the Preferred Reporting Items in Systematic Reviews and Meta-Analyses guideline, the pooled association of targeted ASPs with antimicrobial consumption was measured using multilevel random-effects models. The Effective Public Health Practice Project quality assessment tool was used to assess study quality. MAIN OUTCOMES AND MEASURES: The main outcome measures were proportion of patients receiving an antibiotic prescription and defined daily doses per 100 patient-days. RESULTS: Overall, 52 studies (with 1 794 889 participants) measured the association between ASPs and antimicrobial consumption and were included, with 40 studies conducted in high-income countries and 12 in low- and middle-income countries (LMICs). ASPs were associated with a 10% (95% CI, 4%-15%) reduction in antibiotic prescriptions and a 28% reduction in antibiotic consumption (rate ratio, 0.72; 95% CI, 0.56-0.92). ASPs were also associated with a 21% (95% CI, 5%-36%) reduction in antibiotic consumption in pediatric hospitals and a 28% reduction in World Health Organization watch groups antibiotics (rate ratio, 0.72; 95% CI, 0.56-0.92). CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, ASPs appeared to be effective in reducing antibiotic consumption in both hospital and nonhospital settings. Impact assessment of ASPs in resource-limited settings remains scarce; further research is needed on how to best achieve reductions in antibiotic use in LMICs

Unchecked box Heat from Underground Energy London (Heat FUEL)

This paper aims to introduce a heat recovery scheme that will collect waste energy from the London Underground in Islington, London. The system is based on the installation of an air to water heat exchanger within a ventilation shaft of the London Underground. The heat captured is distributed to a heat pump, which upgrades it to a suitable temperature for reuse and provides low carbon energy to a local district heating network. This paper introduces some of the key aspects of the technical design of this novel urban heat recovery and delivery system. Its theoretical performance is evaluated and compared to the previous heating method used for the buildings supplied by the network. It also provides recommendations for the implementation of future installations for secondary heat recovery and reuse in cities

Quantitative Analysis of Gentamicin Exposure in Neonates and Infants Calls into Question Its Current Dosing Recommendations.

Optimal dosing of gentamicin in neonates is still a matter of debate despite its common use. We identified gentamicin dosing regimens from eight international guidelines and seven Swiss neonatal intensive care units. The dose per administration, the dosing interval, the total daily dose, and the demographic characteristics between guidelines were compared. There was considerable variability with respect to dose (4 to 6 mg/kg), dosing interval (24 h to 48 h), total daily dose (2.5 to 6 mg/kg/day), and patient demographic characteristics that were used to calculate individualized dosing regimens. A model-based simulation study in 1071 neonates was performed to determine the achievement of efficacious peak gentamicin concentrations according to predefined MICs (Cmax/MIC ≥ 10) and safe trough concentrations (Cmin ≤ 2 mg/liter) with recommended dosing regimens. MIC targets of 0.5 and 1 mg/liter were used. Dosing optimization was performed giving priority to the first day of treatment and with the goal of simplifying dosing. Current gentamicin neonatal guidelines allow to achieve effective peak concentrations for MICs ≤ 0.5 mg/liter but not higher. Model-based simulations indicate that to attain peak gentamicin concentrations of ≥10 mg/liter, a dose of 7.5 mg/kg should be administered using an extended dosing interval regimen. Trough concentrations of ≤2 mg/liter can be maintained with a dosing interval of 36 to 48 h in neonates according to gestational and postnatal age. For treatment beyond 3 days, therapeutic drug monitoring is advised to maintain adequate serum concentrations

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. The WHO AWaRe Book amoxicillin dosing guidance can be achieved for infants and older children using only scored 250 mg and 500 mg dispersible tablets (DTs), the WHO recommended child formulation. There is a clear need for wider availability of 250 mg/500 mg dispersible tablets of amoxicillin in both public and private health care sectors, to improve access to essential antibiotics