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The COVID-19 pandemic and related restrictions have potentially impacted the use of antibiotics. We aimed to analyze the use of systemic antibiotics (J01) in ambulatory care in Hungary during two pandemic years, to compare it with pre-COVID levels (January 2015-December 2019), and to describe trends based on monthly utilization. Our main findings were that during the studied COVID-19 pandemic period, compared to the pre-COVID level, an impressive 23.22% decrease in the use of systemic antibiotics was detected in ambulatory care. A significant reduction was shown in the use of several antibacterial subgroups, such as beta-lactam antibacterials, penicillins (J01C, -26.3%), and quinolones (J01M, -36.5%). The trends of antibiotic use moved in parallel with the introduction or revoking of restriction measures with a nadir in May 2020, which corresponded to a 55.46% decrease in use compared to the previous (pre-COVID) year's monthly means. In general, the systemic antibiotic use (J01) was lower compared to the pre-COVID periods' monthly means in almost every studied pandemic month, except for three months from September to November in 2021. The seasonal variation of antibiotic use also diminished. Active agent level analysis revealed an excessive use of azithromycin, even after evidence of ineffectiveness for COVID-19 emerged.

Background: The elderly use antibiotics frequently due to their increasing infection susceptibility. Given the high and increasing proportion of elderly in the population, their antibiotic use is substantial. Objective: This study aimed to compare antibiotic use in the elderly in the ambulatory care sector between Hungary and Sweden. Methods: This retrospective, descriptive, cross-national, comparative study included antibacterial use data from the Hungarian National Health Insurance Fund and the Swedish eHealth Agency. Antibiotic use (anatomical therapeutical chemical: J01) was expressed as the number of prescriptions/1000 inhabitants/year or month and was further stratified by age and sex. Results: Antibiotic exposure was higher in the Hungarian elderly population (649.8 prescriptions/1000 inhabitants/year) compared to its Swedish counterparts (545.0 prescriptions/1000 inhabitants/year). Hungary had a similar scale of antibacterial exposure across all elderly age subgroups, with different trends in males and females, while Sweden had a stepwise increase in antibiotic exposure by age in both sexes. The seasonal fluctuation was high in Hungary and reached a peak of 80.7 prescriptions/1000 inhabitants/month in January 2017, while even antibiotic use was detected throughout the year in Sweden. The pattern of antibiotic use in the elderly considerably differed between the two countries. Penicillin and beta-lactamase combinations, such as co-amoxiclav, were more frequently used in Hungary than in Sweden (19.08% vs 1.83% of corresponding total ambulatory antibiotic use). Likewise, quinolones were more commonly used in Hungary than in Sweden (34.53% vs. 9.98). The elderly in Sweden were mostly prescribed narrow spectra penicillins (26.71% vs. 0.29% in Hungary). Conclusion: This cross-national comparison revealed important differences in all aspects of antibiotic use in the elderly between the two countries. The identical scale and pattern of antibiotic use cannot be anticipated due to the poorer health status of the Hungarian elderly population. However, the substantial differences indicate some room for improvement in the antibiotic prescription for the Hungarian elderly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kusuma, Matuz, Bordás, Juhasz Haverinen, Bahar, Hajdu, Visnyovszki, Ruzsa, Doró, Engi, Csupor and Benko.)

The aim of this study was to analyse characteristics of paediatric antibiotic use in ambulatory care in Hungary. Data on antibiotics for systemic use dispensed to children (0-19 years) were retrieved from the National Health Insurance Fund. Prescribers were categorised by age and specialty. Antibiotic use was expressed as the number of prescriptions/100 children/year or month. For quality assessment, the broad per narrow (B/N) ratio was calculated as defined by the European Surveillance of Antimicrobial Consumption (ESAC) network. Paediatric antibiotic exposure was 108.28 antibiotic prescriptions/100 children/year and was the highest in the age group 0-4 years. Sex differences had heterogenous patterns across age groups. The majority of prescriptions were issued by primary care paediatricians (PCP). The use of broad-spectrum agents dominated, co-amoxiclav alone being responsible for almost one-third of paediatric antibiotic use. Elderly physicians tended to prescribe less broad-spectrum agents. Seasonal variation was found to be substantial: antibiotic prescribing peaked in January with 16.6 prescriptions/100 children/month, while it was the lowest in July with 4 prescriptions/100 children/month. Regional variation was prominent with an increasing west to east gradient (max: 175.6, min: 63.8 prescriptions/100 children/year). The identified characteristics of paediatric antibiotic use suggest that prescribing practice should be improved.

Összefoglaló. Bevezetés: Az antibiotikumok észszerű alkalmazása kulcsfontosságú a hatékonyságuk megőrzésében és a néhol kritikus méreteket öltő antibiotikumrezisztencia visszaszorításában. Célkitűzés: A hazai ambuláns antibiotikumfelhasználás jellemzőinek, trendjeinek bemutatása. Módszer: A 2010 és 2019 közötti időszakra vonatkozó, dobozszámban kifejezett ambuláns szisztémás antibiotikumfelhasználási adatokat - a WHO 2019. évi indexe alapján - "defined daily dose" (DDD - napi átlagdózis) egységbe konvertáltuk. Standardizált technikai egységünk a DDD/1000 fő/nap volt (DID). Az antibiotikumfelhasználás értékelésére nemzetközileg elfogadott minőségi indikátorokat alkalmaztunk. Eredmények: Az antibiotikumfelhasználás mértéke kismértékű ingadozást mutatott (min.: 12,9 DID, max.: 14,7 DID), viszont a szezonális ingadozás a teljes megfigyelt időszakban jelentős mértékű volt. A széles versus szűk spektrumú béta-laktámok és makrolidek felhasználási hányadosa évről évre tovább emelkedett (2010: 13,3 vs. 2019: 71,6), a fluorokinolonok alkalmazási aránya továbbra is meghatározó (2010: 14,3%, 2019: 14,5%). A vizsgált 12 minőségi indikátor közül a tanulmány nyitó évében 4, a tanulmány záró évében 6 indikátor esetében a legkedvezőtlenebbül teljesítő európai országok közé tartoztunk. Megbeszélés: A hazai antibiotikumalkalmazás mértéke európai mérce szerint nem magas, de csökkentésére látszik lehetőség; mintázata szuboptimális, és az évek során kedvezőtlen irányba változott. Következtetés: A kapott antibiotikumfelhasználási adatok s azok értelmezése alapján rendkívül sürgető morális kötelesség a szakmai és hatósági intervenciókra épülő hazai antibiotikumstratégia és -akcióterv mielőbbi kidolgozása, implementálása. Orv Hetil. 2022; 163(4): 140-149., Introduction: Prudent antibiotic use is an important tool to preserve their effectiveness as well as reverse and confine antibiotic resistance., Objective: To evaluate the trends and characteristics of Hungarian outpatient antibiotic use., Methods: Crude, package level antibiotic sales data for the period 2010-2019 were converted into DDD (defined daily dose) and were standardized for 1000 inhabitants and per year (ATC-DDD index, version 2019). Internationally validated drug-specific quality indicators were used to evaluate antibiotic use., Results: The scale of antibiotic use was stagnating with minimal fluctuation (min.: 12.9 DID, max.: 14.7 DID), and with high intra-year seasonality index. The ratio of the consumption of broad to narrow spectrum beta-lactams and macrolides increased gradually from year to year (2010: 13.3 vs. 2019: 71.6) and the relative consumption of fluoroquinolones is still remarkable (2010: 14.3%, 2019: 14.5%). Out of the twelve surveyed drug-specific quality indicators in the first and last year of analysis, we were ranked among the weakest European countries in the case of four and six indicators, respectively., Discussion: The scale of Hungarian outpatient antibiotic use is not high, in European comperison, but has some reserve capacity for reduction. The pattern of Hungarian antibiotic use is suboptimal and had further decreased quality through the years., Conclusion: Based on the recorded data of antibiotic use and their interpretation, the development of national antibiotic strategy (including both professional and authority interventions) is a pressing moral obligation. Orv Hetil. 2021; 163(4): 140-149.

Aims: Subunit interactions at the cytoplasmic domain interface (CD-I) have recently been shown to control gating in inward rectifier potassium channels. Here we report the novel KCNJ2 variant p.Glu293Lys that has been found in a patient with Andersen-Tawil syndrome type 1 (ATS1), causing amino acid substitution at the CD-I of the inward rectifier potassium channel subunit Kir2.1. Neither has the role of Glu293 in gating control been investigated nor has a pathogenic variant been described at this position. This study aimed to assess the involvement of Glu293 in CD-I subunit interactions and to establish the pathogenic role of the p.Glu293Lys variant in ATS1., Methods and Results: The p.Glu293Lys variant produced no current in homomeric form and showed dominant-negative effect over wild-type (WT) subunits. Immunocytochemical labelling showed the p.Glu293Lys subunits to distribute in the subsarcolemmal space. Salt bridge prediction indicated the presence of an intersubunit salt bridge network at the CD-I of Kir2.1, with the involvement of Glu293. Subunit interactions were studied by the NanoLuc® Binary Technology (NanoBiT) split reporter assay. Reporter constructs carrying NanoBiT tags on the intracellular termini produced no bioluminescent signal above background with the p.Glu293Lys variant in homomeric configuration and significantly reduced signals in cells co-expressing WT and p.Glu293Lys subunits simultaneously. Extracellularly presented reporter tags, however, generated comparable bioluminescent signals with heteromeric WT and p.Glu293Lys subunits and with homomeric WT channels., Conclusions: Loss of function and dominant-negative effect confirm the causative role of p.Glu293Lys in ATS1. Co-assembly of Kir2.1 subunits is impaired in homomeric channels consisting of p.Glu293Lys subunits and is partially rescued in heteromeric complexes of WT and p.Glu293Lys Kir2.1 variants. These data point to an important role of Glu293 in mediating subunit assembly, as well as in gating of Kir2.1 channels., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)