Consensus group on the design, analysis and reporting of antibiotic stewardship trials – MRC

Improving antibiotic stewardship [Interview] Professor Martin Llewelyn and Dr Valentijn Schweitzer discuss antibiotic stewardship and explain why there is an urgent need to develop recommendations for better research in this fiel

Aims and challenges of building national trainee networks in clinical microbiology and infectious disease disciplines

Trainees represent the medical practice of tomorrow. Interactions and collaborations at the early stage in career will strengthen the future of our specialties, clinical microbiology and infectious diseases. Trainee networks at the national level help access the best education and career opportunities. The aim of this collaborative white paper between the Trainee Association of European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and four national trainee networks is to discuss the motivation for building such networks and offer guidance for their creation and sustainability even during a health crisis.Publisher PDFPeer reviewe

Non-COVID-19 respiratory viral infection

Implemented control measures brought about by the coronavirus disease 2019 (COVID-19) pandemic have changed the prevalence of other respiratory viruses, often relegating them to a secondary plan. However, it must not be forgotten that a diverse group of viruses, including other human coronaviruses, rhinoviruses, respiratory syncytial virus, human metapneumoviruses, parainfluenza and influenza, continue to be responsible for a large burden of disease. In fact, they are among the most common causes of acute upper and lower respiratory tract infections globally. Viral respiratory infections can be categorised in several ways, including by clinical syndrome or aetiological agent. We describe their clinical spectrum. Distinctive imaging features, advances in microbiological diagnosis and treatment of severe forms are also discussed.info:eu-repo/semantics/publishedVersio

Does plasmid-based beta-lactam resistance increase E. coli infections: Modelling addition and replacement mechanisms

Infections caused by antibiotic-resistant bacteria have become more prevalent during past decades. Yet, it is unknown whether such infections occur in addition to infections with antibiotic-susceptible bacteria, thereby increasing the incidence of infections, or whether they replace such infections, leaving the total incidence unaffected. Observational longitudinal studies cannot separate both mechanisms. Using plasmid-based beta-lactam resistant E. coli as example we applied mathematical modelling to investigate whether seven biological mechanisms would lead to replacement or addition of infections. We use a mathematical neutral null model of individuals colonized with susceptible and/or resistant E. coli, with two mechanisms implying a fitness cost, i.e., increased clearance and decreased growth of resistant strains, and five mechanisms benefitting resistance, i.e., 1) increased virulence, 2) increased transmission, 3) decreased clearance of resistant strains, 4) increased rate of horizontal plasmid transfer, and 5) increased clearance of susceptible E. coli due to antibiotics. Each mechanism is modelled separately to estimate addition to or replacement of antibiotic-susceptible infections. Fitness costs cause resistant strains to die out if other strain characteristics are maintained equal. Under the assumptions tested, increased virulence is the only mechanism that increases the total number of infections. Other benefits of resistance lead to replacement of susceptible infections without changing the total number of infections. As there is no biological evidence that plasmid-based beta-lactam resistance increases virulence, these findings suggest that the burden of disease is determined by attributable effects of resistance rather than by an increase in the number of infections

Molecular Characterization and Clinical Relevance of Taxonomic Reassignment of Staphylococcus schleiferi Subspecies into Two Separate Species, Staphylococcus schleiferi and Staphylococcus coagulans.

Staphylococcus schleiferi is an opportunistic pathogen in humans and dogs. Recent taxonomic reassignment of its subspecies (S. schleiferi subsp. schleiferi and S. schleiferi subsp. coagulans) into two separate species (S. schleiferi and S. coagulans) lacks supporting data for diagnostic implications and clinical relevance. We aimed to confirm the reclassification of S. schleiferi by using genomic and matrix-Assisted laser desorption ionization-time of flight (MALDI-TOF) data for a large set of isolates from humans and animals to investigate their molecular epidemiology and clinical relevance. Routine MALDI-TOF analysis and Illumina sequencing were performed on 165 S. schleiferi isolates from the Netherlands. With 33 publicly available genomes, the study included 198 genomes from 149 dogs, 34 humans, and 15 other sources. The Type Strain Genome Server was used to identify species in the genomes, and the MALDI-TOF MS database was extended to improve species differentiation. MALDI-TOF did not discriminate between S. schleiferi and S. coagulans. Genome phylogeny distinguished the two species in two monophyletic clusters. S. schleiferi isolates originated from humans, while S. coagulans isolates were found in animals and three human isolates clustering with the animal isolates. The sialidase B gene (nanB) was a unique marker gene for S. schleiferi, whereas the chrA gene was exclusive for S. coagulans. The mecA gene was exclusively detected in S. coagulans, as were the lnu(A), blaZ, erm(B/C), tet(O/M), and aac(69)-Aph(299) genes. The MALDI-TOF database extension did not improve differentiation between the two species. Even though our whole-genome sequencing- based approach showed clear differentiation between these two species, it remains critical to identify S. schleiferi and S. coagulans correctly in routine diagnostics. IMPORTANCE This study clearly shows that S. schleiferi is a concern in human hospital settings, whereas S. coagulans predominantly causes infections in animals. S. coagulans is more resistant to antibiotics and can sometimes transmit to humans via exposure to infected dogs. Even though genome-based methods can clearly differentiate the two species, current diagnostic methods used routinely in clinical microbiology laboratories cannot distinguish the two bacterial species

Improving community-acquired pneumonia treatment by antimicrobial stewardship

Antibiotic resistance is a global health threat, with overuse of antibiotics being one of its main drivers. Antimicrobial stewardship is needed to reduce inappropriate use of antibiotics. In hospitals, a substantial proportion of antibiotics is prescribed for pneumonia. Therefore, improving guideline adherence for this infection is an appealing target of antimicrobial stewardship. However, both effectiveness and safety of antimicrobial stewardship interventions in community-acquired pneumonia have not been unequivocally demonstrated. This thesis describes the methodology of studies evaluating antimicrobial stewardship interventions and discusses ways it may be improved. It investigates whether antimicrobial stewardship is effective in reducing broad-spectrum antibiotic use in patients with moderate-severe community-acquired pneumonia without compromising patient outcomes. Lastly, it explores optimal antibiotic treatment strategies in adult patients with moderate-severe community-acquired pneumonia

Improving community-acquired pneumonia treatment by antimicrobial stewardship

Antibiotic resistance is a global health threat, with overuse of antibiotics being one of its main drivers. Antimicrobial stewardship is needed to reduce inappropriate use of antibiotics. In hospitals, a substantial proportion of antibiotics is prescribed for pneumonia. Therefore, improving guideline adherence for this infection is an appealing target of antimicrobial stewardship. However, both effectiveness and safety of antimicrobial stewardship interventions in community-acquired pneumonia have not been unequivocally demonstrated. This thesis describes the methodology of studies evaluating antimicrobial stewardship interventions and discusses ways it may be improved. It investigates whether antimicrobial stewardship is effective in reducing broad-spectrum antibiotic use in patients with moderate-severe community-acquired pneumonia without compromising patient outcomes. Lastly, it explores optimal antibiotic treatment strategies in adult patients with moderate-severe community-acquired pneumonia

Plasma cytokine profile on admission related to aetiology in Community Acquired Pneumonia

Background: Potentially unnecessary antibiotic use for community-acquired pneumonia (CAP) contributes to selection of antibiotic-resistant pathogens. Cytokine expression at the time that treatment is started may assist in identifying patients not requiring antibiotics. We determined plasma cytokine patterns in patients retrospectively categorized as strict viral, pneumococcal or combined viral-bacterial CAP. Objective: To investigate whether cytokine-based prediction models can be used to differentiate strict viral CAP from other aetiologies at admission. Methods: From 344 hospitalized CAP patients, 104 patients were categorized as viral CAP (n = 17), pneumococcal CAP (n = 48) and combined bacterial-viral CAP (n = 39). IL-6, IL-10, IL-27, IFN-γ and C-reactive protein (CRP) were determined on admission in plasma. Prediction of strict viral aetiology was explored with two multivariate regression models and ROC curves. Results: Viral pneumonia was predicted by logistic regression using multiple cytokine levels (IL-6, IL-27 and CRP) with an AUC of 0.911 (95% CI: 0.852-0.971, P <.001). For the same patients the AUC of CRP was 0.813 (95% CI: 0.728-0.898, P <.001). Conclusions: This study demonstrated differences in cytokine expression in selected CAP patients between viral and bacterial aetiology. Prospective validation studies are warranted

Plasma cytokine profile on admission related to aetiology in community-acquired pneumonia

Background: Potentially unnecessary antibiotic use for community-acquired pneumonia (CAP) contributes to selection of antibiotic-resistant pathogens. Cytokine expression at the time that treatment is started may assist in identifying patients not requiring antibiotics. We determined plasma cytokine patterns in patients retrospectively categorized as strict viral, pneumococcal or combined viral-bacterial CAP. Objective: To investigate whether cytokine-based prediction models can be used to differentiate strict viral CAP from other aetiologies at admission. Methods: From 344 hospitalized CAP patients, 104 patients were categorized as viral CAP (n = 17), pneumococcal CAP (n = 48) and combined bacterial-viral CAP (n = 39). IL-6, IL-10, IL-27, IFN-γ and C-reactive protein (CRP) were determined on admission in plasma. Prediction of strict viral aetiology was explored with two multivariate regression models and ROC curves. Results: Viral pneumonia was predicted by logistic regression using multiple cytokine levels (IL-6, IL-27 and CRP) with an AUC of 0.911 (95% CI: 0.852-0.971, P <.001). For the same patients the AUC of CRP was 0.813 (95% CI: 0.728-0.898, P <.001). Conclusions: This study demonstrated differences in cytokine expression in selected CAP patients between viral and bacterial aetiology. Prospective validation studies are warranted