ORCID Profile
0000-0002-3564-8603
Current Organisation
University of Zurich
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Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.EJIM.2022.04.028
Abstract: Guidance for blood culture (BC) collection is limited. Inappropriate BC collection may be associated with potentially harmful consequences for the patient such as unnecessary laboratory testing, treatment and additional costs. The aim of the study was to assess the appropriateness of BC collection and related knowledge and attitude of precribers. We conducted a single-center quality control study to assess the appropriateness of BC collection according to the local guidelines in a Swiss university hospital in 2020 by combining three different approaches: point prevalence, patient-in idual longitudinal and diseases-related analysis. Second, we conducted a survey regarding BC collection practices and knowledge among physicians in two non-university and one university hospital using an 18-item electronic questionnaire. We analyzed 1114 BC collected in 344 patients. Approximately 40% of the BCs were collected inappropriately, in particular in diseases with low pretest probability of bacteremia such as non-severe community acquired pneumonia (CAP). Follow-up blood culture (FUBC) collection was inappropriate in 60%. Growth of a relevant pathogen was more frequently observed in appropriately than in inappropriately collected BCs (18% vs. 3%, p < 0.001). In the survey, uncertainty concerning the need of index BC collection was high in non-severe CAP and uncomplicated cellulitis. Almost half of the BCs was not collected according to the guidelines, especially in non-severe CAP and in case of FUBCs. Substantial uncertainty among physicians regarding BC ordering practices was identified. The implementation of diagnostic stewardship programs may improve BC collection practices, increase adherence to local guidelines, and may help reducing unnecessary diagnostics and treatment.
Publisher: Public Library of Science (PLoS)
Date: 19-03-2021
DOI: 10.1371/JOURNAL.PPAT.1009374
Abstract: The first case of SARS-CoV-2 in Basel, Switzerland was detected on February 26 th 2020. We present a phylogenetic study to explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26 th until March 23 rd . We sequenced SARS-CoV-2 naso-oropharyngeal swabs from 746 positive tests that were performed at the University Hospital Basel during the study period. We successfully generated 468 high quality genomes from unique patients and called variants with our COVID-19 Pipeline (COVGAP), and analysed viral genetic ersity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. Epidemiological data from patient questionnaires was used to facilitate the interpretation of phylogenetic observations. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected first on March 2 nd , although the first s le identified belonged to B.1.1. Within B.1, 68·2% of our s les fall within a clade defined by the SNP C15324T (‘Basel cluster’), including 157 identical sequences at the root of the ‘Basel cluster’, some of which we can specifically trace to regional spreading events. We infer the origin of B.1-C15324T to mid-February in our tri-national region. The other genomes map broadly over the global phylogenetic tree, showing several introduction events from and/or dissemination to other regions of the world via travellers. Family transmissions can also be traced in our data. A single lineage variant dominated the outbreak in the Basel area while other lineages, such as the first (B.1.1), did not propagate. A mass gathering event was the predominant initial source of cases, with travel returners and family transmissions to a lesser extent. We highlight the importance of adding specific questions to epidemiological questionnaires, to obtain data on attendance of large gatherings and their locations, as well as travel history, to effectively identify routes of transmissions in up-coming outbreaks. This phylogenetic analysis in concert with epidemiological and contact tracing data, allows connection and interpretation of events, and can inform public health interventions. Trial Registration: ClinicalTrials.gov NCT04351503 .
Publisher: Cold Spring Harbor Laboratory
Date: 30-07-2020
DOI: 10.1101/2020.07.30.228411
Abstract: Early administration of effective antimicrobial treatments is critical for the outcome of infections. Antimicrobial resistance testing enables the selection of optimal antibiotic treatments, but current culture-based techniques take up to 72 hours. We have developed a novel machine learning approach to predict antimicrobial resistance directly from MALDI-TOF mass spectra profiles of clinical s les. We trained calibrated classifiers on a newly-created publicly available database of mass spectra profiles from clinically most relevant isolates with linked antimicrobial susceptibility phenotypes. The dataset combines more than 300,000 mass spectra with more than 750,000 antimicrobial resistance phenotypes from four medical institutions. Validation against a panel of clinically important pathogens, including Staphylococcus aureus , Escherichia coli , and Klebsiella pneumoniae , resulting in AUROC values of 0.8, 0.74, and 0.74 respectively, demonstrated the potential of using machine learning to substantially accelerate antimicrobial resistance determination and change of clinical management. Furthermore, a retrospective clinical case study found that implementation of this approach would have resulted in a beneficial change in the clinical treatment in 88% (8/9) of cases. MALDI-TOF mass spectra based machine learning may thus be an important new tool for antibiotic stewardship.
Publisher: Cold Spring Harbor Laboratory
Date: 05-09-2020
DOI: 10.1101/2020.09.01.20186155
Abstract: The first case of SARS-CoV-2 in Basel, Switzerland, was detected on February 26 th 2020. We present a phylogenetic longitudinal study and explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26 th until March 23 rd . We sequenced SARS-CoV-2 from naso-oropharyngeal swabs, generated 468 high quality genomes, and called variants with our COVID-19 Pipeline (COVGAP). We analysed viral genetic ersity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected from March 2 nd , although the first lineage identified was B.1.1. Within B.1, a clade containing 68·2% of our s les, defined by the SNP C15324T, suggests local spreading events. We infer the geographic origin of this mutation to our tri-national region. The remaining genomes map broadly over the global phylogenetic tree, evidencing several events of introduction from and/or dissemination to other regions of the world. We also observe family transmission events. A single lineage dominated the outbreak in the City of Basel while other lineages such as the first (B1.1) did not propagate. Thus spreading events seem to have contributed most to viral spread, while travel returners and family transmissions were better controlled by the recommended measures. This phylogenetic analysis enriches epidemiological and contact tracing data, allowing connection of seemingly unconnected events, and can inform public health interventions. No dedicated funding was used for this work.
Publisher: Microbiology Society
Date: 29-06-2021
Abstract: Lymphogranuloma venereum (LGV), the invasive infection of the sexually transmissible infection (STI) Chlamydia trachomatis , is caused by strains from the LGV biovar, most commonly represented by ompA -genotypes L2b and L2. We investigated the ersity in LGV s les across an international collection over seven years using typing and genome sequencing. LGV-positive s les ( n =321) from eight countries collected between 2011 and 2017 (Spain n =97, Netherlands n =67, Switzerland n =64, Australia n =53, Sweden n =37, Hungary n =31, Czechia n =30, Slovenia n =10) were genotyped for pmpH and ompA variants. All were found to contain the 9 bp insertion in the pmpH gene, previously associated with ompA -genotype L2b. However, analysis of the ompA gene shows ompA -genotype L2b ( n =83), ompA -genotype L2 ( n =180) and several variants of these ( n =52 12 variant types), as well as other/mixed ompA -genotypes ( n =6). To elucidate the genomic ersity, whole genome sequencing (WGS) was performed from selected s les using SureSelect target enrichment, resulting in 42 genomes, covering a ersity of ompA -genotypes and representing most of the countries s led. A phylogeny of these data clearly shows that these ompA -genotypes derive from an ompA -genotype L2b ancestor, carrying up to eight SNPs per isolate. SNPs within ompA are overrepresented among genomic changes in these s les, each of which results in an amino acid change in the variable domains of OmpA (major outer membrane protein, MOMP). A reversion to ompA -genotype L2 with the L2b genomic backbone is commonly seen. The wide ersity of ompA -genotypes found in these recent LGV s les indicates that this gene is under immunological selection. Our results suggest that the ompA -genotype L2b genomic backbone is the dominant strain circulating and evolving particularly in men who have sex with men (MSM) populations.
Publisher: Cold Spring Harbor Laboratory
Date: 04-01-2021
DOI: 10.1101/2020.12.28.20248663
Abstract: Antiviral treatments for COVID-19 have involved many repurposed drugs. Currently, SARS-CoV-2 RNA-dependent RNA polymerase (RdRp, encoded by nsp12-nsp7-nsp8 ) has been targeted by numerous inhibitors with debated clinical impact. Among these, remdesivir has been conditionally approved for the treatment of COVID-19 patients. Although the emergence of antiviral resistance, an indirect proxy for antiviral efficacy, poses a considerable healthcare threat, an evolutionary perspective on emerging resistant mutants is still lacking. Here we show that SARS-CoV-2 RdRp is under purifying selection, that potential escape mutations are rare, and unlikely to lead to viral fitness loss. In more than 56,000 viral genomes from 105 countries dating from December 2019 to July 2020 we found negative selective pressure affecting nsp12 (Tajima’s D = −2.62), with potential antiviral escape mutations in only 0.3% of sequenced genomes. Those affected known key residues, such as Nsp12:Val473 and Nsp12:Arg555. Of the potential escape mutations found globally, in silico structural models show that this rarely implies loss of stability in RdRp. No potential escape mutation were found in our local cohort of remdesivir treated patients from the first wave (n=8). Our results indicate that RdRp is a suitable drug target, and that remdesivir does not seem to exert high selective pressure. Our study could be the starting point of a larger monitoring effort of drug resistance throughout the COVID-19 pandemic. We recommend the application of repetitive genome sequencing of SARS-CoV-2 from patients treated with antivirals to provide early insights into the evolution or antiviral resistance.
Publisher: Public Library of Science (PLoS)
Date: 16-03-2023
DOI: 10.1371/JOURNAL.PONE.0282918
Abstract: Blood cultures (BC) are critical for the diagnosis of bloodstream infections, pathogen identification, and resistance testing. Guidelines recommend a blood volume of 8–10 mL per bottle as lower volumes result in decreased sensitivity. We aimed to evaluate factors for non-adherence to recommended volumes and assess the effects on diagnostic performance. From February to April 2020, we measured collected blood volumes by weighing all BC containers from inpatient s les at the University Hospital Basel. Information on BC volumes was merged with clinical and microbiological data, as well as nursing staff schedules. We analyzed factors associated with (i) BC s ling volume, (ii) reaching recommended volumes (≥8 mL), (iii) BC positivity, and (iv) time to positivity using linear and generalized linear mixed effect models. We evaluated a total of 4’118 BC bottles collected from 686 patients. A total of 1’495 (36.3%) of all bottles contained the recommended filling volume of ≥8 mL. Using a central venous and arterial catheter for drawing blood resulted in an increase of filling volume by 0.26 mL (95% CI 0.10, 0.41) and 0.50 mL (95% CI 0.31, 0.69) compared to peripheral venipuncture, respectively. Each additional nursing staff working at the time of blood drawing was associated with 6% higher odds of achieving the recommended filling volume. We found no significant correlation between the filling volume and the positivity rate. Our results indicate critical pre-analytical quality markers linked to BC collection procedures to reach recommended collection volumes. No significant impact on the positivity rate was found.
Publisher: Springer Science and Business Media LLC
Date: 21-03-2018
Publisher: European Centre for Disease Control and Prevention (ECDC)
Date: 13-04-2017
Publisher: MDPI AG
Date: 19-05-2021
DOI: 10.3390/MICROORGANISMS9051094
Abstract: A variety of antiviral treatments for COVID-19 have been investigated, involving many repurposed drugs. Currently, the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp, encoded by nsp12-nsp7-nsp8) has been targeted by numerous inhibitors, e.g., remdesivir, the only provisionally approved treatment to-date, although the clinical impact of these interventions remains inconclusive. However, the potential emergence of antiviral resistance poses a threat to the efficacy of any successful therapies on a wide scale. Here, we propose a framework to monitor the emergence of antiviral resistance, and as a proof of concept, we address the interaction between RdRp and remdesivir. We show that SARS-CoV-2 RdRp is under purifying selection, that potential escape mutations are rare in circulating lineages, and that those mutations, where present, do not destabilise RdRp. In more than 56,000 viral genomes from 105 countries from the first pandemic wave, we found negative selective pressure affecting nsp12 (Tajima’s D = −2.62), with potential antiviral escape mutations in only 0.3% of sequenced genomes. Potential escape mutations included known key residues, such as Nsp12:Val473 and Nsp12:Arg555. Of the potential escape mutations involved globally, in silico structural models found that they were unlikely to be associated with loss of stability in RdRp. No potential escape mutation was found in a local cohort of remdesivir treated patients. Collectively, these findings indicate that RdRp is a suitable drug target, and that remdesivir does not seem to exert high selective pressure. We anticipate our framework to be the starting point of a larger effort for a global monitoring of drug resistance throughout the COVID-19 pandemic.
Publisher: Springer Science and Business Media LLC
Date: 12-2015
No related grants have been discovered for Adrian Egli.