We present a 70‐year‐old female patient diagnosed with epidermal growth factor receptor‐mutated metastatic non‐small cell lung cancer (T4N2M1a), who developed afatinib‐induced toxic epidermal ...necrolysis (TEN). We have also performed a PubMed/Medline literature review to detect other possible cases of TEN/Stevens–Johnson syndrome associated with afatinib treatment and found only 5 other cases reported. To our best knowledge, this is the first case of afatinib‐induced TEN successfully treated with cyclosporine.
Abstract
Objectives
The aim of the study was to assess the impact of the COVID-19 pandemic on antimicrobial consumption (AMC) in the hospital sector in Croatia by analysing data reported to the ...European Surveillance of Antimicrobial Consumption Network (ESAC-Net) between 2016 and 2020.
Methods
AMC was measured as the number of DDDs/1000 inhabitants/day and as the number of DDDs/100 bed days. To assess trends, linear regression was performed. To assess the impact of the pandemic on AMC, the compound annual growth rate was calculated for the years preceding the pandemic based on which AMC for 2020 was forecasted and compared with the actual consumption.
Results
While hospital AMC expressed as DDDs/1000 inhabitants/day between 2019 and 2020 decreased by 17%, when expressed as DDDs/100 bed days, an 8% increase was observed. Hospital consumption of antibacterials for systemic use in the 5 year period did not significantly change when expressed as DDDs/1000 inhabitants/day, while it statistically significantly increased when expressed as DDDs/100 bed days. An increasing trend in consumption of broad-spectrum antimicrobials was found.
Conclusions
During the pandemic there was an increase in hospital AMC with a shift towards broad-spectrum antimicrobials requiring further in-depth qualitative analysis based on patient-level data. Contrasting results obtained using different denominators indicate that the metric DDDs/1000 inhabitants/day is not sensitive enough to evaluate hospital AMC. When assessing hospital AMC, the population under surveillance should be relevant for healthcare context. Antimicrobial stewardship remains one of the most important strategies to tackle antimicrobial resistance and antimicrobial surveillance methods must be as sensitive as possible.
We present a European Union/European Economic Area-wide overview of the changes in consumption of antibacterials for systemic use (ATC J01) in the community between 2019 and 2020 as reported to the ...European Surveillance of Antimicrobial Consumption Network. Overall antibiotic consumption decreased by 18.3% between 2019 and 2020, the largest annual decrease in the network's two-decade history. We observed a strong association between the level of community antibiotic consumption in 2019 and the size of the decrease between 2019 and 2020.
At the 2015 World Health Assembly, UN member states adopted a resolution that committed to the development of national action plans (NAPs) for antimicrobial resistance (AMR). The political ...determination to commit to NAPs and the availability of robust governance structures to assure sustainable translation of the identified NAP objectives from policy to practice remain major barriers to progress. Inter-country variability in economic and political resilience and resource constraints could be fundamental barriers to progressing AMR NAPs. Although there have been regional and global analyses of NAPs from a One Health and policy perspective, a global assessment of the NAP objectives targeting antimicrobial use in human populations is needed. In this Health Policy, we report a systematic evidence synthesis of existing NAPs that are aimed at tackling AMR in human populations. We find marked gaps and variability in maturity of NAP development and operationalisation across the domains of: (1) policy and strategic planning; (2) medicines management and prescribing systems; (3) technology for optimised antimicrobial prescribing; (4) context, culture, and behaviours; (5) operational delivery and monitoring; and (6) patient and public engagement and involvement. The gaps identified in these domains highlight opportunities to facilitate sustainable delivery and operationalisation of NAPs. The findings from this analysis can be used at country, regional, and global levels to identify AMR-related priorities that are relevant to infrastructure needs and contexts.
Surveillance of antimicrobial consumption (AMC) is important to address inappropriate use. AMC data for countries in the European Union (EU) and European Economic Area (EEA) and Eastern European and ...Central Asian countries were compared to provide future guidance.
Analyses of 2014-2018 data from 30 EU/EEA countries of the European Surveillance of Antibiotic Consumption network (ESAC-Net) and 15 countries of the WHO Regional Office for Europe (WHO Europe) AMC Network were conducted using the Anatomical Therapeutic Chemical (ATC) classification and Defined Daily Dose (DDD) methodology. Total consumption (DDD per 1000 inhabitants per day) of antibacterials for systemic use (ATC group J01), relative use (percentages), trends over time, alignment with the WHO Access, Watch, Reserve (AWaRe) classification, concordance with the WHO global indicator (60% of total consumption should be Access agents), and composition of the drug utilization 75% (DU75%) were calculated.
In 2018, total consumption of antibacterials for systemic use (ATC J01) ranged from 8.9 to 34.1 DDD per 1000 inhabitants per day (population-weighted mean for ESAC-Net 20.0, WHO Europe AMC Network 19.6, ESAC-Net Study Group, and WHO Europe AMC Network Study Group). ESAC-Net countries consumed more penicillins (J01C; 8.7 versus 6.3 DDD per 1000 inhabitants per day), more tetracyclines (J01A; 2.2 versus 1.2), less cephalosporins (J01D; 2.3 versus 3.8) and less quinolones (J01M; 1.7 versus 3.4) than WHO Europe AMC Network countries. Between 2014 and 2018, there were statistically significant reductions in total consumption in eight ESAC-Net countries. In 2018, the relative population-weighted mean consumption of Access agents was 57.9% for ESAC-Net and 47.4% for the WHO Europe AMC Network. For each year during 2014-2018, 14 ESAC-Net and one WHO Europe AMC Network countries met the WHO global monitoring target of 60% of total consumption being Access agents. DU75% analyses showed differences in the choices of agents in the two networks.
Although total consumption of antibacterials for systemic use was similar in the two networks, the composition of agents varied substantially. The greater consumption of Watch group agents in WHO Europe AMC Network countries suggests opportunities for improved prescribing. Significant decreases in consumption in several ESAC-Net countries illustrate the value of sustained actions to address antimicrobial resistance.
Antibiotic stewardship is a necessity given the worldwide antimicrobial resistance crisis. Outpatient antibiotic use represents around 90% of total antibiotic use, with more than half of these ...prescriptions being either unnecessary or inappropriate. Efforts to improve antibiotic prescribing need to incorporate two complementary strategies: changing healthcare professionals' behaviour, and modifying the healthcare system. In this review, we present a broad perspective on antibiotic stewardship in primary care in high and high-middle income country settings, focussing on studies published in the last five years. We present the limitations of available literature, discuss perspectives, and provide suggestions for where future work should be concentrated.
Immunotherapy has improved the prognosis of metastatic melanoma patients, although most patients do not achieve a complete response. While specific gut microbiome and dietary habits might influence ...treatment success, there is a lack of concordance between the studies, potentially due to dichotomizing patients only into responders and non-responders. The aim of this study was to elucidate whether metastatic melanoma patients with complete and sustained response to immunotherapy exhibit differences in gut microbiome composition among themselves, and whether those differences were associated with specific dietary habits. Shotgun metagenomic sequencing revealed that patients who exhibited a complete response after more than 9 months of treatment (late responders) exhibited a significantly higher beta-diversity (
= 0.02), with a higher abundance of
(LDA 3.548,
= 0.010),
(LDA 3.392,
= 0.024), and lower abundance of
(
= 0.04) compared to early responders. Furthermore, late responders exhibited a different diet profile, with a significantly lower intake of proteins and sweets and a higher intake of flavones (
< 0.05). The research showed that metastatic melanoma patients with a complete and sustained response to immunotherapy were a heterogeneous group. Patients with a late complete response exhibited microbiome and dietary habits which were previously associated with an improved response to immunotherapy.
Studies suggest that the incidence of coinfections in patients with the coronavirus disease 2019 (COVID-19) is low, but a large number of patients receive antimicrobials during hospitalisation. This ...may fuel a rise in antimicrobial resistance (AMR). We conducted a multicentre point-prevalence survey in seven tertiary university hospitals (in medical wards and intensive care units) in Croatia, Italy, Serbia and Slovenia. Of 988 COVID-19 patients, 521 were receiving antibiotics and/or antifungals (52.7%; range across hospitals: 32.9-85.6%) on the day of the study. Differences between hospitals were statistically significant (χ
(6,
= 988) = 192.57,
< 0.001). The majority of patients received antibiotics and/or antifungals within 48 h of admission (323/521, 62%; range across hospitals: 17.4-100%), their most common use was empirical (79.4% of prescriptions), and pneumonia was the main indication for starting the treatment (three-quarters of prescriptions). The majority of antibiotics prescribed (69.9%) belonged to the "Watch" group of the World Health Organization AWaRe classification. The pattern of antimicrobial use differed across hospitals. The data show that early empiric use of broad-spectrum antibiotics is common in COVID-19 patients, and that the pattern of antimicrobial use varies across hospitals. Judicious use of antimicrobials is warranted to prevent an increase in AMR.
To decrease the incidence and resistance rates of extended-spectrum β-lactamases (ESBL)
(KP) by restriction of the use of third-generation cephalosporins (3GCs) and fluoroquinolones.
Consumption of ...3GCs, fluoroquinolones, and carbapenems in association with ertapenem and fluoroquinolone-resistant KP isolates, were analyzed in 21 months by autoregressive integrated moving average models. A follow-up analysis was performed 5 years later.
Consumption of 3GCs decreased significantly during the postintervention period. Their restriction was associated with a decrease in ertapenem-resistant KP isolates by 17.5%. Fluoroquinolone, 3GCs, and carbapenem use did not significantly predict the percentage of ertapenem-resistant KP isolates. Fluoroquinolone, but not cephalosporin use, significantly predicted the percentage of fluoroquinolone-resistant isolates, with an increase of 1 defined daily dose (DDD) of fluoroquinolone/100 occupied bed-days (OBDs) corresponding to a 0.32% increase of fluoroquinolone-resistant isolates (
= 0.008). A decrease of 1 DDD of carbapenem/100 OBD was associated with a 16.94% increase of fluoroquinolone-resistant isolates (
= 0.007). Five years later, the consumption of all three antimicrobial classes increased significantly compared with the 2011-2013 period, whereas ertapenem-resistant KP rates significantly decreased.
This study may bring a valuable contribution to the understanding of the intricate association between antibiotic consumption and bacterial resistance. Reporting a spectrum of different results could present a useful basis for more profound research of various interventions' effects.
Cilj: Procijeniti spremnost za racionalno propisivanje antimikrobnih lijekova među diplomantima četiriju hrvatskih medicinskih fakulteta temeljem samoprocjene. Nadalje, ustvrditi i raspraviti ...eventualno prisutne nejednakosti među edukacijskim kurikulumima medicinskih fakulteta. Ispitanici i metode: Svi studenti završne godine studija na svim četirima hrvatskim medicinskim fakultetima (Osijek, Rijeka, Split i Zagreb) mogli su sudjelovati u ovom presječnom istraživanju. Korišten je validirani upitnik radne skupine ESGAP Student-PREPARE. Riječ je o upitniku od 47 čestica, a uključuje pitanja o demografskim odrednicama, samoprocijenjenoj spremnosti za racionalno propisivanje antimikrobnih lijekova, percepciji o korisnosti različitih metoda poučavanja te percipiranoj potrebi za daljnjom edukacijom iz ove tematike. Rezultati: Stopa odaziva po pojedinim fakultetima bila je u rasponu od 15,71% do 31,33%. Razina samoprocijenjene „sveukupne spremnosti“ (engl. global preparedness score, GPS) za racionalno propisivanje antimikrobnih lijekova po fakultetima iznosila je redom: Osijek 48,82; Zagreb 53,56; Rijeka 57,14 te Split 66,28. Prosječni GPS (56,45) u 2019. u Hrvatskoj nije bio statistički značajno različit od vrijednosti u 2015. godini (62,66). Splitski su studenti imali statistički značajno bolje rezultate u 3/27 kurikularnih područja, dok za preostala područja statistički značajna razlika nije pronađena. Većina je diplomanata (73,68% – 100%) izrazila potrebu za dodatnom edukacijom iz ove tematike. Samoprocijenjena dostupnost/korisnost interaktivnijih metoda poučavanja bila je veća na splitskom fakultetu. Zaključak: Hrvatski diplomanti medicine po završetku studija generalno se ne osjećaju dovoljno spremnima za samostalno propisivanje antimikrobnih lijekova koje im predstoji u skorašnjoj kliničkoj praksi. Osjetne interregionalne diskrepancije u spremnosti studenata za racionalno propisivanje antimikrobnih lijekova nisu pronađene, međutim uočene su značajnije razlike po pitanju samoprocijenjene dostupnosti/korisnosti pojedinih metoda poučavanja među fakultetima.
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