The role of microbiology and pharmacy departments in the stewardship of antibiotic prescribing in European hospitals

This observational, cross-sectional study describes the role played by clinical microbiology and pharmacy departments in the stewardship of antibiotic prescribing in European hospitals. A total of 170 acute care hospitals from 32 European countries returned a questionnaire on antibiotic policies and practices implemented in 2001. Data on antibiotic use, expressed as De.ned Daily Doses per 100 occupied bed-days (DDD/100 BD) were provided by 139 hospitals from 30 countries. A total of 124 hospitals provided both datasets. 121 (71%) of Clinical Microbiology departments and 66 (41%) of Pharmacy departments provided out of hours clinical advice. 70 (41%) of microbiology/infectious disease specialists and 28 (16%) of pharmacists visited wards on a daily basis. The majority of laboratories provided monitoring of blood cultures more than once per day and summary data of antibiotic susceptibility testing (AST) for empiric prescribing (86% and 73% respectively). Most of the key laboratory and pharmacy-led initiatives examined did not vary signi.cantly by geographical location. Hospitals from the North and West of Europe were more likely to examine blood cultures more than once daily compared with other regions (p < 0.01). Hospitals in the North were least likely routinely to report susceptibility results for restricted antibiotics compared to those in the South-East and Central/Eastern Europe (p < 0.01). Hospital wards in the North were more likely to hold antibiotic stocks (100%) compared with hospitals in the South-East which were least likely (39%) (p < 0.001). Conversely, hospital pharmacies in the North were least likely to dispense antibiotics on an individual patient basis (16%) compared with hospital pharmacies from Southern Europe (60%) (p = 0.01). Hospitals that routinely reported susceptibility results for restricted antibiotics had signi.cantly lower median total antibiotic use in 2001 (p < 0.01). Hospitals that provided prescribing advice outside normal working hours had signi.cantly higher antibiotic use compared with institutions that did not provide this service (p = 0.01). A wide range of antibiotic stewardship measures was practised in the participating hospitals in 2001, although there remains great scope for expansion of those overseen by pharmacy departments. Most hospitals had active antibiotic stewardship programmes led by specialists in infection, although there is no evidence that these were associated with reduced antibiotic consumption. There was also no evidence that pharmacy services reduced the amount of antibiotics prescribed.The ARPAC study was funded by the European Commission (project QLK2-CT-2001-00915). F.M. MacKenzie was supported by the European Study Group on Antibiotic Policies to write this manuscript

Trained Immunity or Tolerance: Opposing Functional Programs Induced in Human Monocytes After Engagement of Various Pattern Recognition Receptors

Upon priming with Candida albicans or with the fungal cell wall component β-glucan, monocytes respond with an increased cytokine production upon restimulation, a phenomenon termed trained immunity. In contrast, the prestimulation of monocytes with lipopolysaccharide has long been known to induce tolerance. Because the vast majority of commensal microorganisms belong to bacterial or viral phyla, we sought to systematically investigate the functional reprogramming of monocytes induced by the stimulation of pattern recognition receptors (PRRs) with various bacterial or viral ligands. Monocytes were functionally programmed for either enhanced (training) or decreased (tolerance) cytokine production, depending on the type and concentration of ligand they encountered. The functional reprogramming of monocytes was also associated with cell shape, granulocity, and cell surface marker modifications. The training effect required p38- and Jun N-terminal protein kinase (JNK)-mediated mitogen-activated protein kinase (MAPK) signaling, with specific signaling patterns directing the functional fate of the cell. The long-term effects on the function of monocytes were mediated by epigenetic events, with both histone methylation and acetylation inhibitors blocking the training effects. In conclusion, our experiments identify the ability of monocytes to acquire adaptive characteristics after prior activation with a wide variety of ligands. Trained immunity and tolerance are two distinct and opposing functional programs induced by the specific microbial ligands engaging the monocytes

Mycobacterium tuberculosis Beijing genotype strains associated with febrile response to treatment.

DNA fingerprinting has demonstrated predominance of the Beijing genotype among Mycobacterium tuberculosis strains isolated in Southeast Asia. We prospectively examined the occurrence of Beijing genotype strains in tuberculosis patients in Indonesia. Early in treatment, patients infected with Beijing genotype strains more often had fever unrelated to disease severity, toxicity, or drug resistance, indicating that Beijing genotype strains may have specific pathogenic properties

Control Measures Used during Lymphogranuloma Venereum Outbreak, Europe

The degree of preparedness may affect the ability to respond quickly and to control an outbreak

Dexamethasone attenuates interferon-related cytokine hyperresponsiveness in COVID-19 patients

Background: Dexamethasone improves the survival of COVID-19 patients in need of supplemental oxygen therapy. Although its broad immunosuppressive effects are well-described, the immunological mechanisms modulated by dexamethasone in patients hospitalized with COVID-19 remain to be elucidated.Objective: We combined functional immunological assays and an omics-based approach to investigate the in vitro and in vivo effects of dexamethasone in the plasma and peripheral blood mononuclear cells (PBMCs) of COVID-19 patients.Methods: Hospitalized COVID-19 patients eligible for dexamethasone therapy were recruited from the general care ward between February and July, 2021. Whole blood transcriptomic and targeted plasma proteomic analyses were performed before and after starting dexamethasone treatment. PBMCs were isolated from healthy individuals and COVID-19 patients and stimulated with inactivated SARS-CoV-2 ex vivo in the presence or absence of dexamethasone and transcriptome and cytokine responses were assessed.Results: Dexamethasone efficiently inhibited SARS-CoV-2-induced in vitro expression of chemokines and cytokines in PBMCs at the transcriptional and protein level. Dexamethasone treatment in COVID-19 patients resulted in down-regulation of genes related to type I and II interferon (IFN) signaling in whole blood immune cells. In addition, dexamethasone attenuated circulating concentrations of secreted interferon-stimulating gene 15 (ISG15) and pro-inflammatory cytokines and chemokines correlating with disease severity and lethal outcomes, such as tumor necrosis factor (TNF), interleukin-6 (IL-6), chemokine ligand 2 (CCL2), C-X-C motif ligand 8 (CXCL8), and C-X-C motif chemokine ligand 10 (CXCL10). In PBMCs from COVID-19 patients that were stimulated ex vivo with multiple pathogens or Toll-like receptor (TLR) ligands, dexamethasone efficiently inhibited cytokine responses.Conclusion: We describe the anti-inflammatory impact of dexamethasone on the pathways contributing to cytokine hyperresponsiveness observed in severe manifestations of COVID-19, including type I/II IFN signaling. Dexamethasone could have adverse effects in COVID-19 patients with mild symptoms by inhibiting IFN responses in early stages of the disease, whereas it exhibits beneficial effects in patients with severe clinical phenotypes by efficiently diminishing cytokine hyperresponsiveness.</p

Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors

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