Projects & Collaborations 5 foundShow per page10 10 20 50 Routes of transmission of ESBL-producing Enterobacterales in a tertiary academic care center Research Project | 1 Project MembersNo Description available NCCR AntiResist: New approaches to combat antibiotic-resistant bacteria Umbrella Project | 32 Project MembersAntibiotics are powerful and indispensable drugs to treat life threatening bacterial infections such as sepsis or pneumonia. Antibiotics also play a central role in many other areas of modern medicine, in particular to protect patients with compromised immunity during cancer therapies, transplantations or surgical interventions. These achievements are now at risk, with the fraction of bacterial pathogens that are resistant to one or more antibiotics steadily increasing. In addition, development of novel antimicrobials lags behind, suffering from inherently high attrition rates in particular for drug candidates against the most problematic Gram-negative bacteria. Together, these factors increasingly limit the options clinicians have for treating bacterial infections. The overarching goal of NCCR AntiResist is to elucidate the physiological properties of bacterial pathogens in infected human patients in order to find new ways of combatting superbugs. Among the many societal, economic, and scientific factors that impact on the development of alternative strategies for antibiotic discovery, our limited understanding of the physiology and heterogeneity of bacterial pathogens in patients ranks highly. Bacteria growing in tissues of patients experience environments very different from standard laboratory conditions, resulting in radically different microbial physiology and population heterogeneity compared to conditions generally used for antibacterial discovery. There is currently no systematic strategy to overcome this fundamental problem. This has resulted in: (i) suboptimal screens that identify new antibiotics, which do not target the special properties of bacteria growing within the patient; (ii) an inability to properly evaluate the efficacy of non-conventional antibacterial strategies; (iii) missed opportunities for entirely new treatment strategies. This NCCR utilizes patient samples from ongoing clinical studies and establishes a unique multidisciplinary network of clinicians, biologists, engineers, chemists, computational scientists and drug developers that will overcome this problem. We are excited to merge these disciplines in order to determine the properties of pathogens infecting patients, establish conditions in the lab that reproduce these properties and utilize these in-vitro models for antimicrobial discovery and development. In addition, clinical-trial networks and the pharmaceutical industry have major footprints in antimicrobial R&D. Exploiting synergies between these players has great potential for making transformative progress in this critical field of human health. This NCCR maintains active collaborations with Biotech SMEs and large pharmaceutical companies with the goal to: accelerate antibiotic discovery by providing relevant read-outs for early prioritization of compounds; enable innovative screens for non-canonical strategies such as anti-virulence inhibitors and immunomodulators; identify new antibacterial strategies that effectively combat bacteria either by targeting refractory subpopulations or by synergizing with bacterial stresses imposed by the patients' own immune system. This NCCR proposes a paradigm shift in antibiotic discovery by investigating the physiology of bacterial pathogens in human patients. This knowledge will be used to develop assays for molecular analyses and drug screening under relevant conditions and to accelerate antibacterial discovery, improve treatment regimens, and uncover novel targets for eradicating pathogens. Through this concerted effort, this NCCR will make a crucial and unique contribution to winning the race against superbugs. The cumulative incidence of seizures during 21 days after new use of oral antibiotics - a cohort study Research Project | 9 Project MembersUse of antibiotics, drugs to cure bacterial infections, has repeatedly been associated with the occurrence of epileptic seizures (abnormal activity in the brain affecting a person's behavior, consciousness or appearance). Various types of antibiotics have been associated with different risks of epileptic seizures. Generally, the risk of epileptic seizure seems to be highest when high doses of antibiotics are used (for example in hospital), or when patients have impaired kidney function, brain disorders, fever, brain infections, or infections in which bacteria are distributed throughout the body. However, it is not clear whether antibiotics are associated with an increased risk of epileptic seizures when taken at usual outpatient (prescribed by the general practitioner) doses. The goal of this study is to quantify the risk of new-onset epileptic seizures in children and adult patients who are newly prescribed oral (taken by mouth) antibiotics by a general practitioner. We further plan to investigate the potential roles of the type of antibiotic, the antibiotic dose, the patients' age, kidney function, underlying type of infection, and pre-existing drug dependence, metabolic disturbances, or brain disorders. Clostridium difficile: Transmissibility and genotypic features Research Project | 2 Project MembersPatients undergoing antimicrobiol therapy in hospitals suffer frequently from diarrhea due to Clostridium difficile. New strains of this bacteria emerged during the last decade and are associated with increased mortality from 2 - 20 %. The pathogenesis of the disease is complex: it requires exposure to C. difficile, an alteration of the microbial flora in the gut, and a lack of antibody against this pathogen. Antibiotics are the leading source for changing of the colonic flora putting even the non-immunocompromised patients at risk for developing C. difficile associated diarrhea (CDAD). The new strains are called PCR Ribotyp 027 and PCR Ribotyp 078. The key features of these strains are the release of toxins that ultimately lead to the disease. Multiple outbreaks with C. difficile have been published with these 027 and 078 strains. Therefore, public health authorities such as the European and the Centers for disease Control and Prevention (Atlanta, USA) require the isolation of affected patients in hospitals to prevent spread of all C. difficile patients, especially those epidemiologically important cases with PCR Ribotyp 027 and 078. The detection of C. difficile is - as the name implies - difficult. This study will evaluate the rate of transmission of C. difficile, stratified by common strains and those epidemiologically important 027 and 078 strains. Most clinical laboratories in hospital do not isolate C. difficile from clinical specimens, but rely on simple direct toxin detection. Therefore, the epidemiology of C. difficile in Switzerland is unknown because the sensitivity of this test to detect toxin-positive C. difficile is around 50%. In addition, PCR ribotyping is not routinely performed to detect the 027 or 078 strains. The first step of the study is the implementation of state-of-the art methodology to detect strains of C. difficile followed by PCR ribotyping to detect this epidemiologically important strain. Patients exposed to a patient who is identified as a case will be screened for C. difficile. The results of this study will allow to provide a detailed epidemiology of the different C. difficile strains in our institution, and provide an estimate of extend of spread. Our hypothesis is that only these epidemiologically important strains 027 or 078 require contact isolation, and the 95% of all other strains can be placed on standard precautions. This would lead to savings of more than one million Swiss Francs a year per large hospital. It would improve patient comfort and potentially quality of care. In addition, the impact of environmental contamination will be analyzed as well. The results will be compared with the German national database (Leader: Prof. P. Gastmeier, Berlin). In addition, Basel was elected as National reference center for the surveillance of C. difficile in Europe (Leader: J.Kuijper, Leiden, the Netherlands). mayTransmission is linked to contamination of the environment, contaminated hands of healthcare workers Transmission of ESBL-producing Enterobacteriaceae and their mobile genetic elements– identification of sources by whole genome sequencing Research Project | 1 Project MembersSwiss National Science foundation (SNF), project NRP 72 1 1
Routes of transmission of ESBL-producing Enterobacterales in a tertiary academic care center Research Project | 1 Project MembersNo Description available
NCCR AntiResist: New approaches to combat antibiotic-resistant bacteria Umbrella Project | 32 Project MembersAntibiotics are powerful and indispensable drugs to treat life threatening bacterial infections such as sepsis or pneumonia. Antibiotics also play a central role in many other areas of modern medicine, in particular to protect patients with compromised immunity during cancer therapies, transplantations or surgical interventions. These achievements are now at risk, with the fraction of bacterial pathogens that are resistant to one or more antibiotics steadily increasing. In addition, development of novel antimicrobials lags behind, suffering from inherently high attrition rates in particular for drug candidates against the most problematic Gram-negative bacteria. Together, these factors increasingly limit the options clinicians have for treating bacterial infections. The overarching goal of NCCR AntiResist is to elucidate the physiological properties of bacterial pathogens in infected human patients in order to find new ways of combatting superbugs. Among the many societal, economic, and scientific factors that impact on the development of alternative strategies for antibiotic discovery, our limited understanding of the physiology and heterogeneity of bacterial pathogens in patients ranks highly. Bacteria growing in tissues of patients experience environments very different from standard laboratory conditions, resulting in radically different microbial physiology and population heterogeneity compared to conditions generally used for antibacterial discovery. There is currently no systematic strategy to overcome this fundamental problem. This has resulted in: (i) suboptimal screens that identify new antibiotics, which do not target the special properties of bacteria growing within the patient; (ii) an inability to properly evaluate the efficacy of non-conventional antibacterial strategies; (iii) missed opportunities for entirely new treatment strategies. This NCCR utilizes patient samples from ongoing clinical studies and establishes a unique multidisciplinary network of clinicians, biologists, engineers, chemists, computational scientists and drug developers that will overcome this problem. We are excited to merge these disciplines in order to determine the properties of pathogens infecting patients, establish conditions in the lab that reproduce these properties and utilize these in-vitro models for antimicrobial discovery and development. In addition, clinical-trial networks and the pharmaceutical industry have major footprints in antimicrobial R&D. Exploiting synergies between these players has great potential for making transformative progress in this critical field of human health. This NCCR maintains active collaborations with Biotech SMEs and large pharmaceutical companies with the goal to: accelerate antibiotic discovery by providing relevant read-outs for early prioritization of compounds; enable innovative screens for non-canonical strategies such as anti-virulence inhibitors and immunomodulators; identify new antibacterial strategies that effectively combat bacteria either by targeting refractory subpopulations or by synergizing with bacterial stresses imposed by the patients' own immune system. This NCCR proposes a paradigm shift in antibiotic discovery by investigating the physiology of bacterial pathogens in human patients. This knowledge will be used to develop assays for molecular analyses and drug screening under relevant conditions and to accelerate antibacterial discovery, improve treatment regimens, and uncover novel targets for eradicating pathogens. Through this concerted effort, this NCCR will make a crucial and unique contribution to winning the race against superbugs.
The cumulative incidence of seizures during 21 days after new use of oral antibiotics - a cohort study Research Project | 9 Project MembersUse of antibiotics, drugs to cure bacterial infections, has repeatedly been associated with the occurrence of epileptic seizures (abnormal activity in the brain affecting a person's behavior, consciousness or appearance). Various types of antibiotics have been associated with different risks of epileptic seizures. Generally, the risk of epileptic seizure seems to be highest when high doses of antibiotics are used (for example in hospital), or when patients have impaired kidney function, brain disorders, fever, brain infections, or infections in which bacteria are distributed throughout the body. However, it is not clear whether antibiotics are associated with an increased risk of epileptic seizures when taken at usual outpatient (prescribed by the general practitioner) doses. The goal of this study is to quantify the risk of new-onset epileptic seizures in children and adult patients who are newly prescribed oral (taken by mouth) antibiotics by a general practitioner. We further plan to investigate the potential roles of the type of antibiotic, the antibiotic dose, the patients' age, kidney function, underlying type of infection, and pre-existing drug dependence, metabolic disturbances, or brain disorders.
Clostridium difficile: Transmissibility and genotypic features Research Project | 2 Project MembersPatients undergoing antimicrobiol therapy in hospitals suffer frequently from diarrhea due to Clostridium difficile. New strains of this bacteria emerged during the last decade and are associated with increased mortality from 2 - 20 %. The pathogenesis of the disease is complex: it requires exposure to C. difficile, an alteration of the microbial flora in the gut, and a lack of antibody against this pathogen. Antibiotics are the leading source for changing of the colonic flora putting even the non-immunocompromised patients at risk for developing C. difficile associated diarrhea (CDAD). The new strains are called PCR Ribotyp 027 and PCR Ribotyp 078. The key features of these strains are the release of toxins that ultimately lead to the disease. Multiple outbreaks with C. difficile have been published with these 027 and 078 strains. Therefore, public health authorities such as the European and the Centers for disease Control and Prevention (Atlanta, USA) require the isolation of affected patients in hospitals to prevent spread of all C. difficile patients, especially those epidemiologically important cases with PCR Ribotyp 027 and 078. The detection of C. difficile is - as the name implies - difficult. This study will evaluate the rate of transmission of C. difficile, stratified by common strains and those epidemiologically important 027 and 078 strains. Most clinical laboratories in hospital do not isolate C. difficile from clinical specimens, but rely on simple direct toxin detection. Therefore, the epidemiology of C. difficile in Switzerland is unknown because the sensitivity of this test to detect toxin-positive C. difficile is around 50%. In addition, PCR ribotyping is not routinely performed to detect the 027 or 078 strains. The first step of the study is the implementation of state-of-the art methodology to detect strains of C. difficile followed by PCR ribotyping to detect this epidemiologically important strain. Patients exposed to a patient who is identified as a case will be screened for C. difficile. The results of this study will allow to provide a detailed epidemiology of the different C. difficile strains in our institution, and provide an estimate of extend of spread. Our hypothesis is that only these epidemiologically important strains 027 or 078 require contact isolation, and the 95% of all other strains can be placed on standard precautions. This would lead to savings of more than one million Swiss Francs a year per large hospital. It would improve patient comfort and potentially quality of care. In addition, the impact of environmental contamination will be analyzed as well. The results will be compared with the German national database (Leader: Prof. P. Gastmeier, Berlin). In addition, Basel was elected as National reference center for the surveillance of C. difficile in Europe (Leader: J.Kuijper, Leiden, the Netherlands). mayTransmission is linked to contamination of the environment, contaminated hands of healthcare workers
Transmission of ESBL-producing Enterobacteriaceae and their mobile genetic elements– identification of sources by whole genome sequencing Research Project | 1 Project MembersSwiss National Science foundation (SNF), project NRP 72
