The impact of antimicrobial use guidelines on prescription habits in fourteen Flemish small animal practices

A prospective study was performed to explore the prescription habits in fourteen first-line, small animal practices during first consultations of cats and dogs. Consultations one month prior to the implementation of antimicrobial use guidelines and at least 20 days thereafter were examined. Differences in the proportion of consultations during which antimicrobials were prescribed, were assessed. Additionally, changes in the choice of active substance were critically evaluated against the introduced antimicrobial use guidelines. The proportion of consultations where antimicrobials were prescribed decreased in cats and dogs (both -12%) after the introduction of the antimicrobial use guidelines. There was an increase of consultations of cats (+13%) and dogs (+10%) where veterinarians handled according to those guidelines. However, an increase in the prescription of third-choice antimicrobials and highest priority critically important antimicrobials was noticed both in cats (+8% and +12%, respectively) and dogs (both +5%). This unexpected increase invites to create extra awareness amongst prescribers

Reduced availability of voltage-gated sodium channels by depolarization or blockade by tetrodotoxin boosts burst firing and catecholamine release in mouse chromaffin cells

KEY POINTS: Mouse chromaffin cells (MCCs) of the adrenal medulla possess fast-inactivating Nav channels whose availability alters spontaneous action potential firing patterns and the Ca2+ -dependent secretion of catecholamines. Here, we report MCCs expressing large densities of neuronal fast-inactivating Nav1.3 and Nav1.7 channels that carry little or no subthreshold pacemaker currents and can be slowly inactivated by 50% upon slight membrane depolarization. Reducing Nav1.3/Nav1.7 availability by tetrodotoxin or by sustained depolarization near rest leads to a switch from tonic to burst-firing patterns that give rise to elevated Ca2+ -influx and increased catecholamine release. Spontaneous burst firing is also evident in a small percentage of control MCCs. Our results establish that burst firing comprises an intrinsic firing mode of MCCs that boosts their output. This occurs particularly when Nav channel availability is reduced by sustained splanchnic nerve stimulation or prolonged cell depolarizations induced by acidosis, hyperkalaemia and increased muscarine levels. ABSTRACT: Action potential (AP) firing in mouse chromaffin cells (MCCs) is mainly sustained by Cav1.3 L-type channels that drive BK and SK currents and regulate the pacemaking cycle. As secretory units, CCs optimally recruit Ca2+ channels when stimulated, a process potentially dependent on the modulation of the AP waveform. Our previous work has shown that a critical determinant of AP shape is voltage-gated sodium channel (Nav) channel availability. Here, we studied the contribution of Nav channels to firing patterns and AP shapes at rest (-50 mV) and upon stimulation (-40 mV). Using quantitative RT-PCR and immunoblotting, we show that MCCs mainly express tetrodotoxin (TTX)-sensitive, fast-inactivating Nav1.3 and Nav1.7 channels that carry little or no Na+ current during slow ramp depolarizations. Time constants and the percentage of recovery from fast inactivation and slow entry into closed-state inactivation are similar to that of brain Nav1.3 and Nav1.7 channels. The fraction of available Nav channels is reduced by half after 10 mV depolarization from -50 to -40 mV. This leads to low amplitude spikes and a reduction in repolarizing K+ currents inverting the net current from outward to inward during the after-hyperpolarization. When Nav channel availability is reduced by up to 20% of total, either by TTX block or steady depolarization, a switch from tonic to burst firing is observed. The spontaneous occurrence of high frequency bursts is rare under control conditions (14% of cells) but leads to major Ca2+ -entry and increased catecholamine release. Thus, Nav1.3/Nav1.7 channel availability sets the AP shape, burst-firing initiation and regulates catecholamine secretion in MCCs. Nav channel inactivation becomes important during periods of high activity, mimicking stress responses

Differential Roles for L-Type Calcium Channel Subtypes in Alcohol Dependence

It has previously been shown that the inhibition of L-type calcium channels (LTCCs) decreases alcohol consumption, although the contribution of the central LTCC subtypes Cav1.2 and Cav1.3 remains unknown. Here, we determined changes in Cav1.2 (Cacna1c) and Cav1.3 (Cacna1d) mRNA and protein expression in alcohol-dependent rats during protracted abstinence and naive controls using in situ hybridization and western blot analysis. Functional validation was obtained by electrophysiological recordings of calcium currents in dissociated hippocampal pyramidal neurons. We then measured alcohol self-administration and cue-induced reinstatement of alcohol seeking in dependent and nondependent rats after intracerebroventricular (i.c.v.) injection of the LTCC antagonist verapamil, as well as in mice with an inducible knockout (KO) of Cav1.2 in Ca2+/calmodulin-dependent protein kinase parallel to alpha (CaMKII alpha)-expressing neurons. Our results show that Cacna1c mRNA concentration was increased in the amygdala and hippocampus of alcohol-dependent rats after 21 days of abstinence, with no changes in Cacna1d mRNA. This was associated with increased Cav1.2 protein concentration and L-type calcium current amplitudes. Further analysis of Cacna1c mRNA in the CA1, basolateral amygdala (BLA), and central amygdala (CeA) revealed a dynamic regulation over time during the development of alcohol dependence. The inhibition of central LTCCs via i. c. v. administration of verapamil prevented cue-induced reinstatement of alcohol seeking in alcohol-dependent rats. Further studies in conditional Cav1.2-KO mice showed a lack of dependence-induced increase of alcohol-seeking behavior. Together, our data indicate that central Cav1.2 channels, rather than Cav1.3, mediate alcohol-seeking behavior. This finding may be of interest for the development of new antirelapse medications

Antimicrobial use in European acute care hospitals: results from the second point prevalence survey (PPS) of healthcare-associated infections and antimicrobial use, 2016 to 2017

Antimicrobial agents used to treat infections are life-saving. Overuse may result in more frequent adverse effects and emergence of multidrug-resistant microorganisms. In 2016-17, we performed the second point-prevalence survey (PPS) of healthcare-associated infections (HAIs) and antimicrobial use in European acute care hospitals. We included 1,209 hospitals and 310,755 patients in 28 of 31 European Union/European Economic Area (EU/EEA) countries. The weighted prevalence of antimicrobial use in the EU/EEA was 30.5% (95% CI: 29.2-31.9%). The most common indication for prescribing antimicrobials was treatment of a community-acquired infection, followed by treatment of HAI and surgical prophylaxis. Over half (54.2%) of antimicrobials for surgical prophylaxis were prescribed for more than 1 day. The most common infections treated by antimicrobials were respiratory tract infections and the most commonly prescribed antimicrobial agents were penicillins with beta-lactamase inhibitors. There was wide variation of patients on antimicrobials, in the selection of antimicrobial agents and in antimicrobial stewardship resources and activities across the participating countries. The results of the PPS provide detailed information on antimicrobial use in European acute care hospitals, enable comparisons between countries and hospitals, and highlight key areas for national and European action that will support efforts towards prudent use of antimicrobials

Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases

We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment

Resultaten van de tweede ECDC puntprevalentiestudie van antimicrobiële consumptie en zorginfecties in Belgische acute ziekenhuizen in 2017

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Antibiotic use and resistance in Belgium: the impact of two decades of multi-faceted campaigning

: To present an overview of almost two decades of multi-faceted campaigning by the Belgian Antibiotic Policy Coordination Committee (BAPCOC) and partners, and its impact on public and prescribers’ awareness, outpatient antibiotic use, its cost and antimicrobial resistance in Belgium.: Awareness of both public and prescribers was assessed through pre- and post-campaign interviews and surveys. Outpatient antibiotic use was evaluated using national reimbursement data expressed in number of defined daily doses and packages (a good proxy for treatments) per 1000 inhabitants per day (DID and PID, respectively) from July 1997 to June 2018. Its cost was studied using the same data expressed in number of euros per 1000 inhabitants per day. Antimicrobial resistance was evaluated between 1986 and 2017 using national data on the proportion of Streptococcus pneumoniae isolates not susceptible to penicillins, macrolides and tetracyclines.: Antibiotic awareness improved significantly, with general practitioners preferred by 87.5% of respondents as source of information. The Belgian outpatient antibiotic use has decreased by 12.8% in DID and by 42.8% in PID in the 2017-2018 winter compared to the winter before the start of its public awareness campaigns (1999-2000). This evolution coincided with decreasing costs for antibiotics and decreasing antimicrobial resistance. Despite multi-faceted campaigning, outpatient antibiotic use and use of broad-spectrum antibiotics, especially fluoroquinolones and amoxicillin with clavulanic acid, are still high in Belgium.: Almost two decades of multi-faceted campaigning coincide with improvements in antibiotic awareness among the public and prescribers, outpatient antibiotic use and resistance. Nevertheless, additional efforts are needed to reach the targets set in BAPCOC’s national action plan 2014-2019. Therefore, a new national action plan was developed for 2020-2024 using a One Health&nbsp;approach.</p

Antibiotic use and resistance in Belgium: the impact of two decades of multi-faceted campaigning.

: To present an overview of almost two decades of multi-faceted campaigning by the Belgian Antibiotic Policy Coordination Committee (BAPCOC) and partners, and its impact on public and prescribers’ awareness, outpatient antibiotic use, its cost and antimicrobial resistance in Belgium.: Awareness of both public and prescribers was assessed through pre- and post-campaign interviews and surveys. Outpatient antibiotic use was evaluated using national reimbursement data expressed in number of defined daily doses and packages (a good proxy for treatments) per 1000 inhabitants per day (DID and PID, respectively) from July 1997 to June 2018. Its cost was studied using the same data expressed in number of euros per 1000 inhabitants per day. Antimicrobial resistance was evaluated between 1986 and 2017 using national data on the proportion of Streptococcus pneumoniae isolates not susceptible to penicillins, macrolides and tetracyclines.: Antibiotic awareness improved significantly, with general practitioners preferred by 87.5% of respondents as source of information. The Belgian outpatient antibiotic use has decreased by 12.8% in DID and by 42.8% in PID in the 2017-2018 winter compared to the winter before the start of its public awareness campaigns (1999-2000). This evolution coincided with decreasing costs for antibiotics and decreasing antimicrobial resistance. Despite multi-faceted campaigning, outpatient antibiotic use and use of broad-spectrum antibiotics, especially fluoroquinolones and amoxicillin with clavulanic acid, are still high in Belgium.: Almost two decades of multi-faceted campaigning coincide with improvements in antibiotic awareness among the public and prescribers, outpatient antibiotic use and resistance. Nevertheless, additional efforts are needed to reach the targets set in BAPCOC’s national action plan 2014-2019. Therefore, a new national action plan was developed for 2020-2024 using a One Health&nbsp;approach.</p