The WHO Access, Watch, and Reserve (AWaRe) antibiotic classification framework aims to balance appropriate access to antibiotics and stewardship. We aimed to identify how patterns of antibiotic ...consumption in each of the AWaRe categories changed across countries over 15 years.
Antibiotic consumption was classified into Access, Watch, and Reserve categories for 76 countries between 2000, and 2015, using quarterly national sample survey data obtained from IQVIA. We measured the proportion of antibiotic use in each category, and calculated the ratio of Access antibiotics to Watch antibiotics (access-to-watch index), for each country.
Between 2000, and 2015, global per-capita consumption of Watch antibiotics increased by 90·9% (from 3·3 to 6·3 defined daily doses per 1000 inhabitants per day DIDs) compared with an increase of 26·2% (from 8·4 to 10·6 DIDs) in Access antibiotics. The increase in Watch antibiotic consumption was greater in low-income and middle-income countries (LMICs; 165·0%; from 2·0 to 5·3 DIDs) than in high-income countries (HICs; 27·9%; from 6·1 to 7·8 DIDs). The access-to-watch index decreased by 38·5% over the study period globally (from 2·6 to 1·6); 46·7% decrease in LMICs (from 3·0 to 1·6) and 16·7% decrease in HICs (from 1·8 to 1·5), and 37 (90%) of 41 LMICs had a decrease in their relative access-to-watch consumption. The proportion of countries in which Access antibiotics represented at least 60% of their total antibiotic consumption (the WHO national-level target) decreased from 50 (76%) of 66 countries in 2000, to 42 (55%) of 76 countries in 2015.
Rapid increases in Watch antibiotic consumption, particularly in LMICs, reflect challenges in antibiotic stewardship. Without policy changes, the WHO national-level target of at least 60% of total antibiotic consumption being in the Access category by 2023, will be difficult to achieve. The AWaRe framework is an important measure of the effort to combat antimicrobial resistance and to ensure equal access to effective antibiotics between countries.
US Centers for Disease Control and Prevention.
The 2017 WHO Model List of Essential Medicines for Children (EMLc) groups antibiotics as Access, Watch, or Reserve, based on recommendations of their use as first-choice and second-choice empirical ...treatment for the most common infections. This grouping provides an opportunity to review country-level antibiotic consumption and a potential for stewardship. Therefore, we aimed to review 2015 levels of oral antibiotic consumption by young children globally.
We analysed wholesale antibiotic sales in 70 middle-income and high-income countries in 2015. We identified oral antibiotic formulations appropriate for use in young children (defined as child-appropriate formulations CAFs) using wholesale data from the IQVIA-Multinational Integrated Data Analysis System database, and we estimated 2015 antibiotic consumption in reference to the 2017 WHO EMLc Access, Watch, Reserve (AWaRe) antibiotic groups. We used three metrics for assessment of intra-country patterns: access percentage, defined as the number of CAF standard units of Access antibiotics divided by the total number of CAF standard units; amoxicillin index, defined as the number of amoxicillin CAF standard units divided by the total number of CAF standard units; and access-to-watch index, defined as the ratio of Access-to-Watch CAF standard units.
The overall median volume of CAF antibiotic standard units sold in 2015 per country was 74·5 million (IQR 12·4–210·7 million). The median access percentage among the 70 countries was 76·3% (IQR 62·6–84·2). The amoxicillin index was low (median 30·7%, IQR 14·3–47·3). The median access-to-watch index was 6·0 (IQR 3·1–9·8). CAF antibiotic consumption patterns were highly variable between the 70 countries, without a clear difference between high-income and middle-income countries.
Antibiotics in the Access group have a key role in treating young children globally. A simple combination of metrics based on the AWaRe groups can be informative on individual countries' patterns of antibiotic consumption and stewardship opportunities. These metrics could support countries in the development of programmes to improve access to core Access antibiotics, particularly amoxicillin.
Global Antibiotic R&D Partnership (German Federal Ministry of Health, Médecins Sans Frontières, Netherlands Ministry of Health, Welfare and Sport, and UK Department for International Development).
Antibiotic fixed dose combinations (FDCs) can have clinical advantages such as improving effectiveness and adherence to therapy. However, high use of potentially inappropriate FDCs has been reported, ...with implications for antimicrobial resistance (AMR) and toxicity. We used a pharmaceutical database, IQVIA-Multinational Integrated Data Analysis System (IQVIA-MIDAS®), to estimate sales of antibiotic FDCs from 75 countries in 2015. Antibiotic consumption was estimated using standard units (SU), defined by IQVIA as a single tablet, capsule, ampoule, vial or 5ml oral suspension. For each FDC antibiotic, the approval status was assessed by either registration with the United States Food and Drug Administration (US FDA) or inclusion on the World Health Organization (WHO) Essential Medicines List (EML). A total of 119 antibiotic FDCs were identified, contributing 16.7 x 109 SU, equalling 22% of total antibiotic consumption in 2015. The most sold antibiotic FDCs were amoxicillin-clavulanic acid followed by trimethoprim/sulfamethoxazole and ampicillin/cloxacillin. The category with the highest consumption volume was aminopenicillin/β-lactamase inhibitor +/- other agents. The majority of antibiotic FDCs (92%; 110/119) were not approved by the US FDA. Of these, the most sold were ampicillin/cloxacillin, cefixime/ofloxacin and metronidazole/spiramycin. More than 80% (98/119) of FDC antibiotics were not compatible with the 2017 WHO EML. The countries with the highest numbers of FDC antibiotics were India (80/119), China (25/119) and Vietnam (19/119). There is high consumption of FDC antibiotics globally, particularly in middle-income countries. The majority of FDC antibiotic were not approved by either US FDA or WHO EML. International initiatives such as clear guidance from the WHO EML on which FDCs are not appropriate may help to regulate the manufacturing and sales of these antibiotics.
Respiratory syncytial virus (RSV) is a major worldwide cause of morbidity and mortality in children under five years of age. Evidence-based management guidelines suggest that there is no effective ...treatment for RSV lower respiratory tract infection (LRTI) and that supportive care, ie, hydration and oxygenation, remains the cornerstone of clinical management. However, RSV treatments in development in the past decade include 10 vaccines and 11 therapeutic agents in active clinical trials. Maternal vaccination is particularly relevant because the most severe disease occurs within the first 6 months of life, when children are unlikely to benefit from active immunisation. We must optimise the implementation of novel RSV therapeutics by understanding the target populations, showing safety, and striving for acceptable pricing in the context of this worldwide health problem. In this Review, we outline the limitations of RSV LRTI management, the drugs in development, and the remaining challenges related to study design, regulatory approval, and implementation.
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.
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. Coagulase-negative Staphylococcus, Corynebacteria and Bacillus spp. were excluded. Patient-level clinical and laboratory data were not available.
There were 8,319 significant isolates, giving an infection rate of 14.3/1000 patient-days. Infection rates increased from 12.0 to 15.7/1000 patient-days (estimated average yearly change 0.695%CI, 0.5-0.7;p = <0.001). Gram-negative infection rates increased from 4.3 to 10.8/1000 patient-days (estimated average yearly change 0.795%CI,0.6-0.8;p = <0.001). The 2 most commonly isolated Gram-negative organisms were Acinetobacter baumannii (44%) and Klebsiella pneumoniae (39%). Carbapenem resistance was seen in 31% of all Gram-negatives and increased over time (estimated average yearly change 4.8%95%CI,4.2%-5.3%;p<0.001). Gram-positive infection rates decreased (estimated average yearly change -0.195%CI,-0.2- -0.05;p = <0.001). Staphylococcus aureus was the most common Gram-positive isolated. Rates of methicillin-resistant Staphylococcus aureus decreased from 91% to 55%(estimated average yearly change -2.8%95%CI,-3.5%-2%,p< 0.001). Rates of fungal isolates decreased (estimated average yearly change -0.0695%CI,-0.1 --0.02);p = 0.007). Candida parapsilosis (52%) and Candida albicans (35%) were the most common fungi isolated.
There has been a marked overall increase in rates of blood and/or CSF infections, with an absolute increase in Gram-negative infections observed, replacing Gram-positive and fungal pathogens. Extended spectrum beta-lactamase Gram-negative isolates are being replaced by carbapenem resistance, with around one third of all significant Gram-negative isolates now carbapenem resistant. Research into hospital based novel treatment and prevention interventions for neonatal sepsis should be urgently prioritized.
Summary Background Meningitis remains one of the most feared infectious diseases worldwide, yet there are few population-based studies on the epidemiology, causes, or trends over time in meningitis, ...especially in industrialised countries. Our aim was to do such a study using routinely reported data available in England and Wales. Methods In England and Wales, UK National Health Service hospitals routinely report laboratory-confirmed pathogens electronically to Public Health England. Records of all positive bacterial, mycobacterial, and fungal results from cerebrospinal fluid or from blood cultures in patients with clinical meningitis were extracted for analysis. The percentage change in annual incidence was estimated using linear regression analysis of the log of the annual incidence. Findings During 2004–11, 7061 cases of meningitis were reported (mean annual incidence 1·62 per 100 000 people, 95% CI 1·58–1·66), including 2594 cases in children (37%). The incidence of bacterial (1·44 per 100 000 people, 1·41–1·48), fungal (0·09, 0·08–0·10), and mycobacterial (0·09, 0·08–0·09) meningitis remained stable overall and across the age groups, apart from significant year-on-year increases in children younger than 3 months (978 cases; incidence 72·2 per 100 000 people; annual increase 7·4%, 5·1–9·8; p<0·0001) driven mainly by group B streptococci (GBS), and in adults aged 65 years or older (752 cases; incidence 1·2 per 100 000 people; annual increase 3·0%, 1·4–4·8; p<0·0001) primarily because of Escherichia coli . By contrast, meningococcal meningitis rates declined steadily, but remained the most common cause of meningitis in children. Overall, five groups of bacteria accounted for 60% (3790/6286) of bacterial meningitis cases: Neisseria meningitidis (1350 cases, 22%), Streptococcus pneumoniae (1143, 18%), Staphylococcus aureus (652, 10%), GBS (326, 5%), and E coli (319, 5%). Interpretation In England and Wales, laboratory-based surveillance shows a remarkably stable incidence of bacterial, fungal, and mycobacterial meningitis in recent years, although there were differences in individual trends among the main pathogens causing meningitis in different age groups. Funding None.
Background Pneumonia is the most common cause of death in children worldwide, accounting for 15% of all deaths of children under 5 years of age. This review summarises the evidence for the empirical ...antibiotic treatment of community-acquired pneumonia in neonates and children and puts emphasis on publications since the release of the previous WHO Evidence Summary report published in 2014.
Methods A systematic search for systematic reviews and meta-analyses of antibiotic therapy for community-acquired pneumonia was conducted between 1 January 2013 and 10 November 2016.
Results The optimal dosing recommendation for amoxicillin remains unclear with limited pharmacological and clinical evidence. There is limited evidence from surveillance to indicate whether amoxicillin or broader spectrum antibiotics (e.g. third-generation cephalosporins) are being used most commonly for paediatric CAP in different WHO regions. Data are lacking on clinical efficacy in the context of pneumococcal, staphylococcal and mycoplasma disease and the relative contributions of varying first-line and step-down options to the selection of such resistance.
Conclusion Further pragmatic trials are required to optimise management of hospitalised children with severe and very severe pneumonia.
Abstract
Objectives
Appropriate use of and access to antimicrobials are key priorities of global strategies to combat antimicrobial resistance (AMR). The WHO recently classified key antibiotics into ...three categories (AWaRe) to improve access (Access), monitor important antibiotics (Watch) and preserve effectiveness of ‘last resort’ antibiotics (Reserve). This classification was assessed for antibiotic stewardship and quality improvement in English hospitals.
Methods
Using an expert elicitation exercise, antibiotics used in England but not included in the WHO AWaRe index were added to an appropriate category following a workshop consensus exercise with national experts. The methodology was tested using national antibiotic prescribing data and presented by primary and secondary care.
Results
In 2016, 46/108 antibiotics included within the WHO AWaRe index were routinely used in England and an additional 25 antibiotics also commonly used in England were not included in the WHO AWaRe index. WHO AWaRe-excluded and -included antibiotics were reviewed and reclassified according to the England-adapted AWaRE index with the justification by experts for each addition or alteration. Applying the England-adapted AWaRe index, Access antibiotics accounted for the majority (60.9%) of prescribing, followed by Watch (37.9%) and Reserve (0.8%); 0.4% of antibiotics remained unclassified. There was unexplained 2-fold variation in prescribing between hospitals within each AWaRe category, highlighting the potential for quality improvement.
Conclusions
We have adapted the WHO AWaRe index to create a specific index for England. The AWaRe index provides high-level understanding of antibiotic prescribing. Subsequent to this process the England AWaRe index is now embedded into national antibiotic stewardship policy and incentivized quality improvement schemes.
To examine the timing and duration of RSV bronchiolitis hospital admission among term and preterm infants in England and to identify risk factors for bronchiolitis admission.
A population-based birth ...cohort with follow-up to age 1 year, using the Hospital Episode Statistics database.
71 hospitals across England.
We identified 296618 individual birth records from 2007/08 and linked to subsequent hospital admission records during the first year of life.
In our cohort there were 7189 hospital admissions with a diagnosis of bronchiolitis, 24.2 admissions per 1000 infants under 1 year (95%CI 23.7-24.8), of which 15% (1050/7189) were born preterm (47.3 bronchiolitis admissions per 1000 preterm infants (95% CI 44.4-50.2)). The peak age group for bronchiolitis admissions was infants aged 1 month and the median was age 120 days (IQR = 61-209 days). The median length of stay was 1 day (IQR = 0-3). The relative risk (RR) of a bronchiolitis admission was higher among infants with known risk factors for severe RSV infection, including those born preterm (RR = 1.9, 95% CI 1.8-2.0) compared with infants born at term. Other conditions also significantly increased risk of bronchiolitis admission, including Down's syndrome (RR = 2.5, 95% CI 1.7-3.7) and cerebral palsy (RR = 2.4, 95% CI 1.5-4.0).
Most (85%) of the infants who are admitted to hospital with bronchiolitis in England are born at term, with no known predisposing risk factors for severe RSV infection, although risk of admission is higher in known risk groups. The early age of bronchiolitis admissions has important implications for the potential impact and timing of future active and passive immunisations. More research is needed to explain why babies born with Down's syndrome and cerebral palsy are also at higher risk of hospital admission with RSV bronchiolitis.
Despite a high mortality rate in childhood, there is limited evidence on the causes and outcomes of paediatric bloodstream infections from low- and middle-income countries (LMICs). We conducted a ...systematic review and meta-analysis to characterize the bacterial causes of paediatric bloodstream infections in LMICs and their resistance profile.
We searched Pubmed and Embase databases between January 1st 1990 and October 30th 2019, combining MeSH and free-text terms for "sepsis" and "low-middle-income countries" in children. Two reviewers screened articles and performed data extraction to identify studies investigating children (1 month-18 years), with at least one blood culture. The main outcomes of interests were the rate of positive blood cultures, the distribution of bacterial pathogens, the resistance patterns and the case-fatality rate. The proportions obtained from each study were pooled using the Freeman-Tukey double arcsine transformation, and a random-effect meta-analysis model was used.
We identified 2403 eligible studies, 17 were included in the final review including 52,915 children (11 in Africa and 6 in Asia). The overall percentage of positive blood culture was 19.1% 95% CI: 12.0-27.5%; 15.5% 8.4-24.4% in Africa and 28.0% 13.2-45.8% in Asia. A total of 4836 bacterial isolates were included in the studies; 2974 were Gram-negative (63.9% 52.2-74.9) and 1858 were Gram-positive (35.8% 24.9-47.5). In Asia,
typhi (26.2%) was the most commonly isolated pathogen, followed by
(7.7%) whereas in Africa,
(17.8%) and
(16.8%) were predominant followed by
(10.7%).
was more likely resistant to methicillin in Africa (29.5% vs. 7.9%), whereas
was more frequently resistant to third-generation cephalosporins (31.2% vs. 21.2%), amikacin (29.6% vs. 0%) and ciprofloxacin (36.7% vs. 0%) in Asia. The overall estimate for case-fatality rate among 8 studies was 12.7% 6.6-20.2%. Underlying conditions, such as malnutrition or HIV infection were assessed as a factor associated with bacteraemia in 4 studies each.
We observed a marked variation in pathogen distribution and their resistance profiles between Asia and Africa. Very limited data is available on underlying risk factors for bacteraemia, patterns of treatment of multidrug-resistant infections and predictors of adverse outcomes.
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