Point prevalence surveys of antimicrobial use among eight neonatal intensive care units in India: 2016

BACKGROUND: Information about antimicrobial use is scarce and poorly understood among neonatal intensive care units (NICUs) in India. In this study, we describe antimicrobial use in eight NICUs using four point prevalence surveys (PPSs). METHODS: As part of the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children (GARPEC) study, one-day, cross-sectional, hospital-based PPSs were conducted four times between 1 February 2016 and 28 February 2017 in eight NICUs. Using a standardized web-based electronic data entry form, detailed data were collected for babies on antimicrobials. RESULTS: A total of 403 babies were admitted to NICUs across all survey days, and 208 (51.6%) were prescribed one or more antimicrobials. Among 208 babies, 155 (74.5%) were prescribed antimicrobials for treatment of an active infection. Among 155 babies with an active infection, treatment was empiric in 109 (70.3%). Sepsis (108, 49.1%) was the most common reason for prescribing antimicrobials. Amikacin (17%) followed by meropenem (12%) were the two most commonly prescribed antimicrobials. For community-acquired sepsis, piperacillin-tazobactam (17.5%) was the most commonly prescribed drug. A combination of ampicillin and gentamicin was prescribed in only two babies (5%). CONCLUSIONS: The recommended first-line antimicrobial agents, ampicillin and gentamicin, were rarely prescribed in Indian NICUs for community acquired neonatal sepsis

Quality indicators for appropriate antibiotic prescribing in urinary tract infections in children

BACKGROUND: The aim of this study was to define a set of urinary tract infections (UTIs)-specific quality indicators for appropriate prescribing in children and evaluate clinical practices in a district general hospital in Greece. METHODS: The aim of this study was to define a set of urinary tract infections (UTIs)-specific quality indicators for appropriate prescribing in children and evaluate clinical practices in a district general hospital in Greece. METHODS: The aim of this study was to define a set of urinary tract infections (UTIs)-specific quality indicators for appropriate prescribing in children and evaluate clinical practices in a district general hospital in Greece. RESULTS: Twelve quality indicators were adapted or developed for prescribing in childhood UTIs. A broad variety of antibiotics were prescribed for UTIs, with a drug utilization (DU) 90% rate of 6 and 9 different antibiotics for febrile and afebrile UTIs, respectively. Despite the low incidence of multi-drug resistant UTIs in the study period (9/261, 3.4%), broad-spectrum antibiotics were prescribed in 33.5% (164/490) of prescriptions. A total of 62.8% (164/261) of patients were started on empiric combined therapies, while opportunities to de-escalate were missed in 37.8% (62/164) of them. One quarter (67/261, 25.7%) of patients did not fulfil the criteria for receiving treatment, while nearly half of those prescribed prophylaxis (82/175, 46.9%) could have avoided having a prophylaxis prescription. CONCLUSIONS: Our study identified substantial gaps for improvement in antimicrobial prescribing for UTIs in children. The application of the proposed quality indicators could help to limit unnecessary antibiotics use in children with UTI

Assessment of pediatric asthma drug use in three European countries; a TEDDY study.

Asthma drugs are amongst the most frequently used drugs in childhood, but international comparisons on type and indication of use are lacking. The aim of this study was to describe asthma drug use in children with and without asthma in the Netherlands (NL), Italy (IT), and the United Kingdom (UK). We conducted a retrospective analysis of outpatient medical records of children 0-18 years from 1 January 2000 until 31 December 2005. For all children, prescription rates of asthma drugs were studied by country, age, asthma diagnosis, and off-label status. One-year prevalence rates were calculated per 100 children per patient-year (PY). The cohort consisted of 671,831 children of whom 49,442 had been diagnosed with asthma at any time during follow-up. ß2-mimetics and inhaled steroids were the most frequently prescribed asthma drug classes in NL (4.9 and 4.1/100 PY), the UK (8.7 and 5.3/100 PY) and IT (7.2 and 16.2/100 PY), respectively. Xanthines, anticholinergics, leukotriene receptor antagonists, and anti-allergics were prescribed in less than one child per 100 per year. In patients without asthma, ß2-mimetics were used most frequently. Country differences were highest for steroids, (Italy highest), and for ß2-mimetics (the UK highest). Off-label use was low, and most pronounced for ß2-mimetics in children <18 months (IT) and combined ß2-mimetics + anticholinergics in children <6 years (NL). CONCLUSION: This study shows that among all asthma drugs, ß2-mimetics and inhaled steroids are most often used, also in children without asthma, and with large variability between countries. Linking multi-country databases allows us to study country specific pediatric drug use in a systematic manner without being hampered by methodological differences. This study underlines the potency of healthcare databases in rapidly providing data on pediatric drug use and possibly safety

Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe) : an analysis of paediatric survey data from 56 countries

Background Improving the quality of hospital antibiotic use is a major goal of WHO's global action plan to combat antimicrobial resistance. The WHO Essential Medicines List Access, Watch, and Reserve (AWaRe) classification could facilitate simple stewardship interventions that are widely applicable globally. We aimed to present data on patterns of paediatric AWaRe antibiotic use that could be used for local and national stewardship interventions. Methods 1-day point prevalence survey antibiotic prescription data were combined from two independent global networks: the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children and the Global Point Prevalence Survey on Antimicrobial Consumption and Resistance networks. We included hospital inpatients aged younger than 19 years receiving at least one antibiotic on the day of the survey. The WHO AWaRe classification was used to describe overall antibiotic use as assessed by the variation between use of Access, Watch, and Reserve antibiotics, for neonates and children and for the commonest clinical indications. Findings Of the 23 572 patients included from 56 countries, 18305 were children (77.7%) and 5267 were neonates (22.3%). Access antibiotic use in children ranged from 7.8% (China) to 61.2% (Slovenia) of all antibiotic prescriptions. The use of Watch antibiotics in children was highest in Iran (77.3%) and lowest in Finland (23.0%). In neonates, Access antibiotic use was highest in Singapore (100.0%) and lowest in China (24.2%). Reserve antibiotic use was low in all countries. Major differences in clinical syndrome-specific patterns of AWaRe antibiotic use in lower respiratory tract infection and neonatal sepsis were observed between WHO regions and countries. Interpretation There is substantial global variation in the proportion of AWaRe antibiotics used in hospitalised neonates and children. The AWaRe classification could potentially be used as a simple traffic light metric of appropriate antibiotic use. Future efforts should focus on developing and evaluating paediatric antibiotic stewardship programmes on the basis of the AWaRe index. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.Peer reviewe

Gabapentinoid consumption in 65 countries and regions from 2008 to 2018: a longitudinal trend study

Recent studies raised concerns about the increasing use of gabapentinoids in different countries. With their potential for misuse and addiction, understanding the global consumption of gabapentinoids will offer us a platform to examine the need for any interventional policies. This longitudinal trend study utilised pharmaceutical sales data from 65 countries and regions across the world to evaluate the global trends in gabapentinoid consumption between 2008-2018. The multinational average annual percentage change of gabapentinoid consumption was +17.20%, increased from 4.17 defined daily dose per ten thousand inhabitants per day (DDD/TID) in 2008 to 18.26 DDD/TID in 2018. High-income countries had the highest pooled gabapentinoid consumption rate (39.92 DDD/TID) in 2018, which was more than six times higher than the lower-middle income countries (6.11 DDD/TID). The study shows that despite differences in healthcare system and culture, a consistent increase in gabapentinoid consumption is observed worldwide, with high-income countries remaining the largest consumers

Antiseizure medications consumption in 73 countries and regions from 2012 to 2022:a longitudinal trend study

Background: International trends in antiseizure medication use across countries from different geographical regions and income levels remain underexplored. Valproic acid (valproate) use has raised concerns due to its teratogenic risks, with World Health Organisation (WHO) guidelines recommending lamotrigine or levetiracetam as first-line therapy for epilepsy in women and girls of childbearing potential, advising against valproate use in this population. This study aimed to assess multinational trends in antiseizure medication (ASM) consumption from 2012 to 2022 in the context of evolving policy and regulatory actions. Methods: In this longitudinal trend study, we used pharmaceutical sales data of antiseizure medications from the IQVIA-Multinational Integrated Data Analysis System (MIDAS) between January 1, 2012 and December 31, 2022, covering 73 countries/regions. The list of ASMs included in this study was based on the Anatomical Therapeutic Chemical (ATC) Classification, N03A. We obtained the mid-year national/regional population estimates of each country from the United Nations Population Division and the total epilepsy (active idiopathic and secondary epilepsy) population from the Global Burden of Disease Collaborative Network. 41 high-income, 20 upper-middle income and 12 lower-middle-income countries/regions were included in this study. Antiseizure medication consumption rate was expressed as defined daily doses per 10,000 inhabitants per day (DDD/TID). Linear mixed models were used to estimate multinational, regional, and income-level trends in consumption over time. Findings: Multinational antiseizure medication consumption increased throughout the study period, with an average annual percentage change of +2·58% (95% CI +1·85% to +3·32%), rising from 40·96 DDD/TID (31·94-52·52) in 2012 to 52·87 DDD/TID (42·17-66·27) in 2022. The highest change in consumption was in South-eastern Asia (+5·20%, +3·41% to +7·03%), followed by Western Asia (+4·70%, +0·58% to +8·99%) and Southern Asia (+3·80%, +1·52% to +6·14%). Newer generation antiseizure medications such as levetiracetam (+21·72%, +13·86% to +30·11%) and lamotrigine (+7·48%, +6·34% to +8·63%) showed growth in consumption, while consumption of older medications such as phenobarbital (-2·85%, -9·50% to +4·29%), phenytoin (-11·19%, -17·58% to -4·30%), and carbamazepine (-1·09%, -1·95% to -0·23%) declined. In 2022, the consumption rate of high-income countries (88·36 DDD/TID, 71·69-108·90) was more than four times of lower-middle-income countries (15·63 DDD/TID, 8·75-27·91). Valproate remained the most widely used antiseizure medication globally (10·93 DDD/TID, 8·68-13·77) in 2022, with stronger growth observed in lower- (+4·24%, +1·73% to +6·81%) and upper-middle-income (+3·10%, +0·95% to +5·29%) countries, compared with high-income countries (+0·86%, -0·07% to +1·79%). Interpretation: Multinational antiseizure medication use increased between 2012 and 2022, particularly for newer medications like levetiracetam and lamotrigine. Disparities in access to antiseizure medications across countries of varying income levels persist, with valproate consumption remaining predominant. This underscores the urgent need to align prescribing practice with safety guidelines, in order to optimise patient outcomes. Since patient-level characteristics are not available in IQVIA-MIDAS, further research is warranted to examine consumption rates across different population groups. Funding: This study is partially supported by the Laboratory of Data Discovery for Health (D24H) funded by AIR@InnoHK, administered by Innovation and Technology Commission of the Government of Hong Kong Special Administrative Region

Pediatric drug safety signal detection: a new drug-event reference set for performance testing of data-mining methods and systems

BACKGROUND: Better evidence regarding drug safety in the pediatric population might be generated from existing data sources such as spontaneous reporting systems and electronic healthcare records. The Global Research in Paediatrics (GRiP)-Network of Excellence aims to develop pediatric-specific methods that can be applied to these data sources. A reference set of positive and negative drug-event associations is required. OBJECTIVE: The aim of this study was to develop a pediatric-specific reference set of positive and negative drug-event associations. METHODS: Considering user patterns and expert opinion, 16 drugs that are used in individuals aged 0-18 years were selected and evaluated against 16 events, regarded as important safety outcomes. A cross-table of unique drug-event pairs was created. Each pair was classified as potential positive or negative control based on information from the drug's Summary of Product Characteristics and Micromedex. If both information sources consistently listed the event as an adverse event, the combination was reviewed as potential positive control. If both did not, the combination was evaluated as potential negative control. Further evaluation was based on published literature. RESULTS: Selected drugs include ibuprofen, flucloxacillin, domperidone, methylphenidate, montelukast, quinine, and cyproterone/ethinylestradiol. Selected events include bullous eruption, aplastic anemia, ventricular arrhythmia, sudden death, acute kidney injury, psychosis, and seizure. Altogether, 256 unique combinations were reviewed, yielding 37 positive (17 with evidence from the pediatric population and 20 with evidence from adults only) and 90 negative control pairs, with the remainder being unclassifiable. CONCLUSION: We propose a drug-event reference set that can be used to compare different signal detection methods in the pediatric population

System-wide approaches to antimicrobial therapy and antimicrobial resistance in the UK: the AMR-X framework

Antimicrobial resistance (AMR) threatens human, animal, and environmental health. Acknowledging the urgency of addressing AMR, an opportunity exists to extend AMR action-focused research beyond the confines of an isolated biomedical paradigm. An AMR learning system, AMR-X, envisions a national network of health systems creating and applying optimal use of antimicrobials on the basis of their data collected from the delivery of routine clinical care. AMR-X integrates traditional AMR discovery, experimental research, and applied research with continuous analysis of pathogens, antimicrobial uses, and clinical outcomes that are routinely disseminated to practitioners, policy makers, patients, and the public to drive changes in practice and outcomes. AMR-X uses connected data-to-action systems to underpin an evaluation framework embedded in routine care, continuously driving implementation of improvements in patient and population health, targeting investment, and incentivising innovation. All stakeholders co-create AMR-X, protecting the public from AMR by adapting to continuously evolving AMR threats and generating the information needed for precision patient and population care

The burden of bacterial antimicrobial resistance in the WHO African region in 2019: a cross-country systematic analysis

Background A critical and persistent challenge to global health and modern health care is the threat of antimicrobial resistance (AMR). Previous studies have reported a disproportionate burden of AMR in low-income and middle-income countries, but there remains an urgent need for more in-depth analyses across Africa. This study presents one of the most comprehensive sets of regional and country-level estimates of bacterial AMR burden in the WHO African region to date. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen–drug combinations for countries in the WHO African region in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). We obtained data from research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. Findings In the WHO African region in 2019, there were an estimated 1·05 million deaths (95% UI 829 000–1 316000) associated with bacterial AMR and 250000 deaths (192000–325000) attributable to bacterial AMR. The largest fatal AMR burden was attributed to lower respiratory and thorax infections (119 000 deaths [92 000–151 000], or 48% of all estimated bacterial pathogen AMR deaths), bloodstream infections (56000 deaths [37000–82000], or 22%), intra-abdominal infections (26 000 deaths [17 000–39000], or 10%), and tuberculosis (18 000 deaths [3850–39 000], or 7%). Seven leading pathogens were collectively responsible for 821 000 deaths (636 000–1 051 000) associated with resistance in this region, with four pathogens exceeding 100 000 deaths each: Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus. Third-generation cephalosporin-resistant K pneumoniae and meticillin-resistant S aureus were shown to be the leading pathogen–drug combinations in 25 and 16 countries, respectively (53% and 34% of the whole region, comprising 47 countries) for deaths attributable to AMR. Interpretation This study reveals a high level of AMR burden for several bacterial pathogens and pathogen–drug combinations in the WHO African region. The high mortality rates associated with these pathogens demonstrate an urgent need to address the burden of AMR in Africa. These estimates also show that quality and access to health care and safe water and sanitation are correlated with AMR mortality, with a higher fatal burden found in lower resource settings. Our cross-country analyses within this region can help local governments to leverage domestic and global funding to create stewardship policies that target the leading pathogen–drug combinations