Comparison of governance approaches for the control of antimicrobial resistance: Analysis of three European countries

Policy makers and governments are calling for coordination to address the crisis emerging from the ineffectiveness of current antibiotics and stagnated pipe-line of new ones – antimicrobial resistance (AMR). Wider contextual drivers and mechanisms are contributing to shifts in governance strategies in health care, but are national health system approaches aligned with strategies required to tackle antimicrobial resistance? This article provides an analysis of governance approaches within healthcare systems including: priority setting, performance monitoring and accountability for AMR prevention in three European countries: England, France and Germany. Advantages and unresolved issues from these different experiences are reported, concluding that mechanisms are needed to support partnerships between healthcare professionals and patients with democratized decision-making and accountability via collaboration. But along with this multi-stakeholder approach to governance, a balance between regulation and persuasion is needed

Pharmaceutical cognitive enhancement in Greek university students: differences between users and non-users in social cognitive variables, burnout and engagement

Pharmaceutical cognitive enhancement (PCE) represents the non-medical use of prescribed medication for the improvement of cognitive functioning and academic performance. Although there are some studies about PCE prevalence, it is less clear how users and non-users of PCE substances differ with respect to their positive and negative student experiences (e.g., academic burnout, engagement with studies) and in social cognitive variables that relate to decision-making and self-regulation of PCE use. The present study assessed whether students with different experiences of PCE substance use displayed differences in academic burnout, study engagement and social cognitive variables relevant to PCE use. Three hundred and forty seven University students (M age = 22.15, SD = 1.69; 54% females) completed a battery of anonymous questionnaires on academic burnout, engagement with studies, social cognitive variables relevant to PCE use, and self-reported use of PCE substances and non-prescribed nutritional supplements. Three user groups emerged, namely, non-users (51.9%, n = 180), single users of non-prescribed dietary supplements (25.4%, n = 88), and dual users of both non-prescribed dietary supplements and PCE (22.8%, n = 79). Multivariate analysis of variance indicated significant differences among the three user groups in intentions, attitudes, social norms, and anticipated regret towards PCE use. No significant differences were observed with respect to academic burnout and work engagement. The findings show that University students may engage in PCE use independently of their student experiences. Rather, a chemically-assisted performance enhancement mindset seems to differentiate users from non-users of PCE substances

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

Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients

With increasing clinical emergence of multidrug-resistant Gram-negative pathogens and the paucity of new agents to combat these infections, colistin (administered as its inactive prodrug colistin methane-sulfonate [CMS]) has reemerged as a treatment option, especially for critically ill patients. There has been a dearth of pharmacokinetic (PK) data available to guide dosing in critically ill patients, including those on renal replacement therapy. In an ongoing study to develop a population PK model for CMS and colistin, 105 patients have been studied to date; these included 12 patients on hemodialysis and 4 on continuous renal replacement therapy. For patients not on renal replacement, there was a wide variance in creatinine clearance, ranging from 3 to 169 ml/min/1.73 m 2. Each patient was treated with a physician-selected CMS dosage regimen, and 8 blood samples for PK analysis were collected across a dosage interval on day 3 or 4 of therapy. A linear PK model with two compartments for CMS and one compartment for formed colistin best described the data. Covariates included creatinine clearance on the total clearance of CMS and colistin, as well as body weight on the central volume of CMS. Model-fitted parameter estimates were used to derive suggested loading and maintenance dosing regimens for various categories of patients, including those on hemodialysis and continuous renal replacement. Based on our current understanding of colistin PK and pharmacodynamic relationships, colistin may best be used as part of a highly active combination, especially for patients with moderate to good renal function and/or for organisms with MICs of ≥1.0 mg/liter

Diagnostic value of triggering receptor expressed on myeloid cells-1 and C-reactive protein for patients with lung infiltrates: an observational study

<p>Abstract</p> <p>Background</p> <p>Differential diagnosis of patients with lung infiltrates remains a challenge. Triggering receptor expressed on myeloid cells (TREM)-1 is a neutrophil and monocyte receptor up-regulated during infection. The aim of this study was to evaluate the diagnostic accuracy of TREM-1 and of C-reactive protein (CRP) from patients with lung infiltrates to discern community acquired lung infections.</p> <p>Methods</p> <p>68 patients admitted to a medical ward with acute respiratory illness were enrolled in the study. Neutrophil and monocyte TREM-1 expression were measured by flow cytometry, sTREM-1 by an enzyme immunoassay and C-reactive protein by nephelometry. Clinical pulmonary infection score was recorded.</p> <p>Results</p> <p>34 patients were diagnosed with bacterial community acquired pneumonia (group A) and 34 with non-bacterial pulmonary disease (group B). Median serum TREM-1 concentration was 102.09 pg/ml in group A and lower than 15.10 pg/ml (p < 0.0001) in group B. Mean±SE neutrophil TREM-1 expression was 4.67 ± 0.53 MFI in group A and 2.64 ± 0.25 MFI (p = 0.001) in group B. Monocyte TREM-1 expression was 4.2 ± 0.42 MFI in group A and 2.64 ± 0.35 MFI (p = 0.007) in group B and mean±SE CRP was 18.03 ± 2 mg/ml in group A and 7.1 ± 1.54 mg/ml (p < 0.001) in group B. A cut-off of 19.53 pg/ml of sTREM-1 with sensitivity 82.6% and specificity 63% to discriminate between infectious and non-infectious pulmonary infiltrates was found. sTREM-1 at admission greater than 180 pg/ml was accompanied with unfavourable outcome.</p> <p>Conclusion</p> <p>TREM-1 myeloid expression and sTREM-1 are reliable markers of bacterial infection among patients with pulmonary infiltrates; sTREM-1 is a predictor of final outcome.</p

Colistin: recent data on pharmacodynamics properties and clinical efficacy in critically ill patients

Recent clinical studies performed in a large number of patients showed that colistin "forgotten" for several decades revived for the management of infections due to multidrug-resistant (MDR) Gram-negative bacteria (GNB) and had acceptable effectiveness and considerably less toxicity than that reported in older publications. Colistin is a rapidly bactericidal antimicrobial agent that possesses a significant postantibiotic effect against MDR Gram-negative pathogens, such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. The optimal colistin dosing regimen against MDR GNB is still unknown in the intensive care unit (ICU) setting. A better understanding of the pharmacokinetic-pharmacodynamic relationship of colistin is urgently needed to determine the optimal dosing regimen. Although pharmacokinetic and pharmacodynamic data in ICU patients are scarce, recent evidence shows that the pharmacokinetics/pharmacodynamics of colistimethate sodium and colistin in critically ill patients differ from those previously found in other groups, such as cystic fibrosis patients. The AUC:MIC ratio has been found to be the parameter best associated with colistin efficacy. To maximize the AUC:MIC ratio, higher doses of colistimethate sodium and alterations in the dosing intervals may be warranted in the ICU setting. In addition, the development of colistin resistance has been linked to inadequate colistin dosing. This enforces the importance of colistin dose optimization in critically ill patients. Although higher colistin doses seem to be beneficial, the lack of colistin pharmacokinetic-pharmacodynamic data results in difficulty for the optimization of daily colistin dose. In conclusion, although colistin seems to be a very reliable alternative for the management of life-threatening nosocomial infections due to MDR GNB, it should be emphasized that there is a lack of guidelines regarding the ideal management of these infections and the appropriate colistin doses in critically ill patients with and without multiple organ failure

Renal and neurological side effects of colistin in critically ill patients

Colistin is a complex polypeptide antibiotic composed mainly of colistin A and B. It was abandoned from clinical use in the 1970s because of significant renal and, to a lesser extent, neurological toxicity. Actually, colistin is increasingly put forward as salvage or even first-line treatment for severe multidrug-resistant, Gram-negative bacterial infections, particularly in the intensive care setting. We reviewed the most recent literature on colistin treatment, focusing on efficacy and toxicity issues. The method used for literature search was based on a PubMed retrieval using very precise criteria

Efflux pump inhibitors (EPIs) as new antimicrobial agents against Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic human pathogen and one of the leading causes of nosocomial infections worldwide. The difficulty in treatment of pseudomonas infections arises from being multidrug resistant (MDR) and exhibits resistance to most antimicrobial agents due to the expression of different mechanisms overcoming their effects. Of these resistance mechanisms, the active efflux pumps in Pseudomonas aeruginosa that belong to the resistance nodulation division (RND) plays a very important role in extruding the antibiotics outside the bacterial cells providing a protective means against their antibacterial activity. Beside its role against the antimicrobial agents, these pumps can extrude biocides, detergents, and other metabolic inhibitors. It is clear that efflux pumps can be targets for new antimicrobial agents. Peptidomimetic compounds such as phenylalanine arginyl β-naphthylamide (PAβN) have been introduced as efflux pump inhibitors (EPIs); their mechanism of action is through competitive inhibition with antibiotics on the efflux pump resulting in increased intracellular concentration of antibiotic, hence, restoring its antibacterial activity. The advantage of EPIs is the difficulty to develop bacterial resistance against them, but the disadvantage is their toxic property hindering their clinical application. The structure activity relationship of these compounds showed other derivatives from PAβN that are higher in their activity with higher solubility in biological fluids and decreased toxicity level. This raises further questions on how can we compact Pseudomonas infections. Of particular importance, the recent resurgence in the use of older antibiotics such as polymyxins and probably applying stricter control measures in order to prevent their spread in clinical sittings

Management of intra-abdominal infections : recommendations by the WSES 2016 consensus conference

This paper reports on the consensus conference on the management of intra-abdominal infections (IAIs) which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery (WSES) meeting. This document covers all aspects of the management of IAIs. The Grading of Recommendations Assessment, Development and Evaluation recommendation is used, and this document represents the executive summary of the consensus conference findings.Peer reviewe