Publications by authors named "Zinkernagel A"

Group A streptococcal (GAS; aka Streptococcus pyogenes) meningitis is a fulminant disease associated with high morbidity and mortality. To elucidate the mechanisms underlying the invasiveness of GAS in meningitis, we compared GAS isolates derived from five cases of meningitis to otitis and colonizing isolates. We did not observe differences in adherence to and invasion of human brain microvascular endothelial cells, virulence factors activity, or barrier disruption.

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Infective endocarditis (IE) is a life-threatening biofilm-associated infection, yet the factors driving biofilm formation remain poorly understood. Here, we identified the Fsr quorum sensing (QS) system of as a potent negative regulator of IE pathogenesis. Using microfluidic and models, we show that Fsr is induced in late IE when bacteria become shielded from blood flow.

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Introduction: The ability to detect pathogenic bacteria before the onsets of severe respiratory symptoms and to differentiate bacterial infection allows to improve patient-tailored treatment leading to a significant reduction in illness severity, comorbidity as well as antibiotic resistance. As such, this study refines the application of the non-invasive Secondary Electrospray Ionization-High Resolution Mass Spectrometry (SESI-HRMS) methodology for real-time and early detection of human respiratory bacterial pathogens in the respiratory tract of a mouse infection model.

Methods: A real-time analysis of changes in volatile metabolites excreted by mice undergoing a lung infection by Staphylococcus aureus or Streptococcus pneumoniae were evaluated using a SESI-HRMS instrument.

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Article Synopsis
  • - The study aimed to assess improvements in health-related quality of life, as measured by the Short Form-36 (SF-36) scores, for patients in a Swiss Outpatient Parenteral Antimicrobial Therapy (OPAT) program from before discharge to 7-14 days after discharge.
  • - It involved a cohort of 33 patients from a public hospital in Switzerland, who completed a shortened version of the SF-36 questionnaire and additional questions on satisfaction at two different times.
  • - Results indicated significant improvements in three out of four domains (emotional role, social functioning, emotional well-being) and a high patient satisfaction rate, suggesting OPAT programs positively impact patients' health-related quality of life.
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Background: Necrotizing soft tissue infections (NSTIs) are often caused by group A (GAS). As the number of invasive GAS infections decreased during the coronavirus disease 2019 (COVID-19) pandemic restrictions, this study aimed to compare the occurrence of GAS-NSTIs before, during, and after the COVID-19 pandemic restrictions.

Methods: This retrospective cohort study included adult patients with NSTIs admitted to the intensive care unit (ICU) of the University Hospital Zurich, Switzerland, from July 2008 to December 2023.

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Article Synopsis
  • The study investigates the anti-biofilm effects of cell-free supernatants from two probiotic bacterial strains on a human pathobiont responsible for serious infections, including pharyngotonsillitis and necrotizing fasciitis.
  • It finds that these supernatants significantly reduce the survival of both planktonic and biofilm forms of the pathogen, particularly affecting already established biofilms more intensely, suggesting the involvement of glycolipid compounds in this antimicrobial action.
  • The results highlight the need for new therapeutic strategies against biofilm-associated infections, particularly for vulnerable populations, and aim to enhance understanding of lactobacillus properties that could lead to innovative treatment options.
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Group A (GAS) necrotizing fasciitis (NF) is a difficult-to-treat bacterial infection associated with high morbidity and mortality despite extensive surgery and targeted antibiotic treatment. Difficult-to-treat infections are often characterized by the presence of bacteria surviving prolonged antibiotic exposure without displaying genetic resistance, referred to as persisters. In the present study, we investigated the presence of GAS persisters in tissue freshly debrided from patients as well as in an mouse model of NF and examined the phenomenon of antibiotic tolerance.

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Article Synopsis
  • The study focuses on the effectiveness of outpatient parenteral antimicrobial therapy (OPAT) and its role in antimicrobial stewardship (AMS) at the University Hospital of Zurich from November 2018 to September 2022.
  • It analyzed 303 OPAT assignments, with 260 leading to effective treatment; significant cost savings of approximately 9.8 million CHF were achieved by reducing in-hospital stays, while maintaining patient safety and a 77% clinical cure rate.
  • The findings suggest that integrating OPAT within AMS enhances patient care and hospital efficiency, with minimal adverse events and readmissions linked to the treatment.
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The surgical repair of a ruptured tendon faces two major problems: specifically increased fibrous adhesion to the surrounding tissue and inferior mechanical properties of the scar tissue compared to the native tissue. Bacterial attachment to implant materials is an additional problem as it might lead to severe infections and impaired recovery. To counteract adhesion formation, two novel implant materials were fabricated by electrospinning, namely, a random fiber mesh containing hyaluronic acid (HA) and poly(ethylene oxide) (PEO) in a ratio of 1:1 (HA/PEO 1:1) and 1:4 (HA/PEO 1:4), respectively.

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Bacterial infections are a growing global healthcare concern, as an estimated annual 4.95 million deaths are associated with antimicrobial resistance (AMR). Methicillin-resistant is one of the deadliest pathogens and a high-priority pathogen according to the World Health Organization.

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BackgroundWomen are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown.AimWe assessed the impact of sex and gender on PASC in a Swiss population.

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Antimicrobial strategies for musculoskeletal infections are typically first developed with in vitro models. The In Vitro Section of the 2023 Orthopedic Research Society Musculoskeletal Infection international consensus meeting (ICM) probed our state of knowledge of in vitro systems with respect to bacteria and biofilm phenotype, standards, in vitro activity, and the ability to predict in vivo efficacy. A subset of ICM delegates performed systematic reviews on 15 questions and made recommendations and assessment of the level of evidence that were then voted on by 72 ICM delegates.

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Antibiotic resistance and tolerance are substantial healthcare-related problems, hampering effective treatment of bacterial infections. Mutations in the phosphodiesterase GdpP, which degrades cyclic di-3', 5'-adenosine monophosphate (c-di-AMP), have recently been associated with resistance to beta-lactam antibiotics in clinical isolates. In this study, we show that high c-di-AMP levels decreased the cell size and increased the cell wall thickness in mutant strains.

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In microbiology, accessing single-cell information within large populations is pivotal. Here we introduce bio-sCAPA, a technique for patterning bacterial cells in defined geometric arrangements and monitoring their growth in various nutrient environments. We demonstrate bio-sCAPA with a study of subpopulations of antibiotic-tolerant bacteria, known as persister cells, which can survive exposure to high doses of antibiotics despite lacking any genetic resistance to the drug.

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Article Synopsis
  • Scientists are having a tough time treating infections caused by certain bacteria because these bacteria are becoming resistant to common medicines.
  • A special type of enzyme called peptidoglycan hydrolases can help fight these bacteria, as they work quickly without worrying about resistance.
  • The researchers are working on a way to make these enzymes target the exact spot of the infection in bones, even helping to reach bacteria that hide inside cells, to improve treatment.
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Viruses have been present during all evolutionary steps on earth and have had a major effect on human history. Viral infections are still among the leading causes of death. Another public health concern is the increase of non-communicable metabolic diseases in the last four decades.

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Background: Pseudomonas aeruginosa and other Gram-negative bacteria have the ability to persist in moist environments in healthcare settings, but their spread from these areas can result in outbreaks of healthcare-associated infections.

Methods: This study reports the investigation and containment of a multi-drug-resistant P. aeruginosa outbreak in three intensive care units of a Swiss university hospital.

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Staphylococcus aureus carriage is a risk factor for invasive infections. Unique genetic elements favoring the transition from colonizing to invasive phenotype have not yet been identified, and phenotypic adaptation traits are understudied. We therefore assessed phenotypic and genotypic profiles of 11 S.

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Autophagy serves an innate immune function in defending the host against invading bacteria, including group A (GAS). Autophagy is regulated by numerous host proteins, including the endogenous negative regulator calpain, a cytosolic protease. Globally disseminated serotype M1T1 GAS strains associated with high invasive disease potential express numerous virulence factors and resist autophagic clearance.

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Regulated cell death (RCD) and the concomitant release of extracellular traps by neutrophils (NETs) constitute an important antibacterial effector response. Usually, the dynamic processes of RCD and NETs release are assessed independently of each other by either unspecific or time-consuming methods. Here, we describe a flow cytometry-based high-throughput analysis method incorporating neutrophil RCD and NETs release with visual live-imaging conformation upon ex vivo bacterial challenge.

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Aims Of The Study: The goal of this descriptive study was to assess the performance as well as the extent of the clinical impact of rapid automated antimicrobial susceptibility testing in patients with bacteraemia due to Enterobacterales. We also aimed to analyse how rapid automated antimicrobial susceptibility testing influences clinical decision-making.

Methods: This single-centre study conducted at the University Hospital of Zurich included data from all consecutive patients with Enterobacterales bacteraemia from November 2019 to October 2020.

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