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  1. Article ; Online: Enzymatic debridement with bromelain and development of bacteremia in burn injuries: A retrospective cohort study.

    Deplazes, Barla C / Hofmaenner, Daniel A / Scheier, Thomas C / Epprecht, Jana / Mayer, Michelle / Schweizer, Tiziano A / Buehler, Philipp K / Frey, Pascal M / Brugger, Silvio D

    Burns : journal of the International Society for Burn Injuries

    2023  Volume 50, Issue 2, Page(s) 405–412

    Abstract: Background: Debridement is crucial for effective wound management in patients with severe burn injuries, and bromelain, a proteolytic enzyme from pineapple stems, has emerged as a promising alternative for surgery. However, potential links of bromelain ... ...

    Abstract Background: Debridement is crucial for effective wound management in patients with severe burn injuries, and bromelain, a proteolytic enzyme from pineapple stems, has emerged as a promising alternative for surgery. However, potential links of bromelain use to fever and sepsis have raised some concerns. Given the uncertainty as to whether this was caused by infection or other inflammatory sources, we aimed to investigate if the use of topical bromelain was associated with bacteremia.
    Methods: This single-centre retrospective cohort study included critically ill adult patients with severe burn injuries hospitalised at the Burn Center of the University Hospital Zurich between January 2017 and December 2021. Data were collected from two in-hospital electronic medical records databases. Our primary outcome, the association between topical bromelain treatment and the development of bacteremia, was investigated using a competing risk regression model, taking into account the competing risk of death. As a secondary outcome, the relationship between bromelain treatment and overall ICU mortality was examined using a Cox proportional hazards model.
    Results: The study included 269 patients with a median age of 50 years and median burnt total body surface area of 19%. A first bacteremia occurred in 61 patients (23%) after a median time of 6 days. Bromelain treatment was given to 83 (31%) of patients, with 22 (27%) of these developing bacteremia. In the fully adjusted competing risk regression model, no evidence for an association between bromelain treatment and bacteremia was found (SHR 0.79, 95%CI 0.42-1.48, p = 0.47). During hospital stay, 40 (15%) of patients died. There was no significant difference in mortality between patients treated with bromelain and those who were not (HR 0.55, 95%CI 0.26-1.20, p = 0.14). Among the five multidrug-resistant (MDR) pathogens identified, three were found in patients with bromelain treatment.
    Conclusion: Our study did not confirm an association between topical bromelain and bacteremia in patients with severe burn injuries. This finding can inform evidence-based practices by addressing concerns about potential risks of bromelain use, contributing to the development of more effective and safe burn wound management strategies.
    MeSH term(s) Adult ; Humans ; Middle Aged ; Retrospective Studies ; Debridement ; Bromelains/therapeutic use ; Burns/complications ; Bacteremia/drug therapy
    Chemical Substances Bromelains (9001-00-7)
    Language English
    Publishing date 2023-12-12
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 197308-3
    ISSN 1879-1409 ; 0305-4179
    ISSN (online) 1879-1409
    ISSN 0305-4179
    DOI 10.1016/j.burns.2023.12.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Pneumococcal carriage and serotype variation before and after introduction of pneumococcal conjugate vaccines in patients with acute otitis media in Switzerland.

    Allemann, Aurélie / Frey, Pascal M / Brugger, Silvio D / Hilty, Markus

    Vaccine

    2017  Volume 35, Issue 15, Page(s) 1946–1953

    Abstract: Background: Acute otitis media (AOM) is an important cause for antibiotic prescription within the paediatric population and Streptococcus pneumoniae is a major pathogen associated with AOM episodes. This study aimed at analysing the influence of the ... ...

    Abstract Background: Acute otitis media (AOM) is an important cause for antibiotic prescription within the paediatric population and Streptococcus pneumoniae is a major pathogen associated with AOM episodes. This study aimed at analysing the influence of the heptavalent and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) on pneumococcal carriage and serotype distribution in AOM.
    Methods: Nasopharyngeal swabs (NPS) and middle ear fluid (MEF) were collected within a Swiss surveillance study of outpatients from all ages with AOM between 2004 and 2015, covering three vaccination eras (pre-PCV7, PCV7 and PCV13). Samples were cultured for pneumococcal identification, and the association of vaccine era with pneumococcal carriage was investigated by logistic regression analysis adjusting for sociodemographic factors.
    Findings: In total, 3300 NPS and 620 MEF were included in this study. The number of samples from patients with AOM dropped over vaccination eras and S. pneumoniae was less frequently isolated in the PCV13 era as compared to the other two eras. The latest (PCV13) vaccination era was independently associated with a reduced pneumococcal carriage within NPS (adjusted odds ratio 0.65, 95%-CI 0.45-0.94). Investigating serotype epidemiology, vaccine serotypes decreased significantly after the conjugate vaccine introductions with the exception of serotype 3. Within the non-PCV13 serotypes, a particular increase of serogroups 11, 15 and 23 was observed in both NPS and MEF.
    Conclusion: A substantial change in pneumococcal carriage and serotype epidemiology suggests an impact of the conjugate vaccines on pneumococcal AOM in Switzerland.
    Language English
    Publishing date 2017-04-04
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2017.02.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The importance of intravenous immunoglobulin treatment in critically ill patients with necrotizing soft tissue infection: a retrospective cohort study.

    Hofmaenner, Daniel A / Wendel Garcia, Pedro David / Blum, Manuel R / David, Sascha / Schuepbach, Reto A / Buehler, Philipp K / Frey, Pascal M / Zinkernagel, Annelies S / Brugger, Silvio D

    BMC infectious diseases

    2022  Volume 22, Issue 1, Page(s) 168

    Abstract: Background: Necrotizing soft-tissue infections are infections with high mortality. The use of immunoglobulins within a combination therapy including broad-spectrum antibiotics has been debated. We assessed potential benefits of immunoglobulins and ... ...

    Abstract Background: Necrotizing soft-tissue infections are infections with high mortality. The use of immunoglobulins within a combination therapy including broad-spectrum antibiotics has been debated. We assessed potential benefits of immunoglobulins and hypothesized that they were associated with a treatment benefit in a high-resource setting.
    Methods: Patients with necrotizing soft-tissue infection hospitalized in the tertiary intensive care unit of the University Hospital of Zurich, Switzerland, between 2008 and 2020 were included retrospectively. The association between immunoglobulin administration and in-hospital survival, intensive care unit length of stay, the incidences of acute renal failure, acute respiratory distress syndrome and septic shock were analyzed.
    Results: After adjustment for confounders, no difference for in-hospital survival (hazard ratio 2.20, 95% confidence interval [CI] 0.24-20.20, p = 0.5), intensive care unit length of stay (subhazard ratio [SHR] 0.90, CI 0.41-1.98, p = 0.8) and the development of acute respiratory distress syndrome (SHR 1.2, CI 0.36-4.03, p = 0.77) was observed in patients with or without immunoglobulin treatment. The Simplified Acute Physiology Score II, the risk of developing acute renal failure (SHR 2.86, CI 1.33-6.15, p = 0.01) and septic shock (SHR 1.86, CI 1.02-3.40, p = 0.04) was higher in patients treated with immunoglobulins, possibly reflecting a higher disease severity beyond measured confounders.
    Conclusions: No clear evidence for a benefit of immunoglobulins in our cohort with consistent antibiotic use was found. Patients receiving immunoglobulins appeared more severely ill. Complementary to high treatment standards and appropriate antibiotics including beta lactams and protein synthesis inhibitors, immunoglobulins should be administered on a case-to-case basis, at least while more evidence from larger randomized controlled trials is missing.
    MeSH term(s) Critical Illness ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Intensive Care Units ; Retrospective Studies ; Soft Tissue Infections/drug therapy
    Chemical Substances Immunoglobulins, Intravenous
    Language English
    Publishing date 2022-02-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041550-3
    ISSN 1471-2334 ; 1471-2334
    ISSN (online) 1471-2334
    ISSN 1471-2334
    DOI 10.1186/s12879-022-07135-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Critically ill COVID-19 patients with neutralizing autoantibodies against type I interferons have increased risk of herpesvirus disease.

    Busnadiego, Idoia / Abela, Irene A / Frey, Pascal M / Hofmaenner, Daniel A / Scheier, Thomas C / Schuepbach, Reto A / Buehler, Philipp K / Brugger, Silvio D / Hale, Benjamin G

    PLoS biology

    2022  Volume 20, Issue 7, Page(s) e3001709

    Abstract: Autoantibodies neutralizing the antiviral action of type I interferons (IFNs) have been associated with predisposition to severe Coronavirus Disease 2019 (COVID-19). Here, we screened for such autoantibodies in 103 critically ill COVID-19 patients in a ... ...

    Abstract Autoantibodies neutralizing the antiviral action of type I interferons (IFNs) have been associated with predisposition to severe Coronavirus Disease 2019 (COVID-19). Here, we screened for such autoantibodies in 103 critically ill COVID-19 patients in a tertiary intensive care unit (ICU) in Switzerland. Eleven patients (10.7%), but no healthy donors, had neutralizing anti-IFNα or anti-IFNα/anti-IFNω IgG in plasma/serum, but anti-IFN IgM or IgA was rare. One patient had non-neutralizing anti-IFNα IgG. Strikingly, all patients with plasma anti-IFNα IgG also had anti-IFNα IgG in tracheobronchial secretions, identifying these autoantibodies at anatomical sites relevant for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Longitudinal analyses revealed patient heterogeneity in terms of increasing, decreasing, or stable anti-IFN IgG levels throughout the length of hospitalization. Notably, presence of anti-IFN autoantibodies in this critically ill COVID-19 cohort appeared to predict herpesvirus disease (caused by herpes simplex viruses types 1 and 2 (HSV-1/-2) and/or cytomegalovirus (CMV)), which has been linked to worse clinical outcomes. Indeed, all 7 tested COVID-19 patients with anti-IFN IgG in our cohort (100%) suffered from one or more herpesviruses, and analysis revealed that these patients were more likely to experience CMV than COVID-19 patients without anti-IFN autoantibodies, even when adjusting for age, gender, and systemic steroid treatment (odds ratio (OR) 7.28, 95% confidence interval (CI) 1.14 to 46.31, p = 0.036). As the IFN system deficiency caused by neutralizing anti-IFN autoantibodies likely directly and indirectly exacerbates the likelihood of latent herpesvirus reactivations in critically ill patients, early diagnosis of anti-IFN IgG could be rapidly used to inform risk-group stratification and treatment options. Trial Registration: ClinicalTrials.gov Identifier: NCT04410263.
    MeSH term(s) Autoantibodies ; COVID-19 ; Critical Illness ; Cytomegalovirus Infections ; Herpes Simplex ; Humans ; Immunoglobulin G ; Interferon Type I ; SARS-CoV-2
    Chemical Substances Autoantibodies ; Immunoglobulin G ; Interferon Type I
    Language English
    Publishing date 2022-07-05
    Publishing country United States
    Document type Clinical Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3001709
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  5. Article: Quantifying Variation in Bacterial Reproductive Fitness: a High-Throughput Method.

    Frey, Pascal M / Baer, Julian / Bergada-Pijuan, Judith / Lawless, Conor / Bühler, Philipp K / Kouyos, Roger D / Lemon, Katherine P / Zinkernagel, Annelies S / Brugger, Silvio D

    mSystems

    2021  Volume 6, Issue 1

    Abstract: To evaluate changes in reproductive fitness of bacteria, e.g., after acquisition of antimicrobial resistance, a low-cost high-throughput method to analyze bacterial growth on agar is desirable for broad usability. In our bacterial quantitative fitness ... ...

    Abstract To evaluate changes in reproductive fitness of bacteria, e.g., after acquisition of antimicrobial resistance, a low-cost high-throughput method to analyze bacterial growth on agar is desirable for broad usability. In our bacterial quantitative fitness analysis (BaQFA), arrayed cultures are spotted on agar and photographed sequentially while growing. These time-lapse images are analyzed using a purpose-built open-source software to derive normalized image intensity (NI) values for each culture spot. Subsequently, a Gompertz growth model is fitted to NI values, and fitness is calculated from model parameters. To represent a range of clinically important pathogenic bacteria, we used different strains of
    Language English
    Publishing date 2021-02-02
    Publishing country United States
    Document type Journal Article
    ISSN 2379-5077
    ISSN 2379-5077
    DOI 10.1128/mSystems.01323-20
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  6. Article ; Online: Bacterial colonization of handheld devices in a tertiary care setting: a hygiene intervention study.

    Frey, Pascal M / Marti, Grischa R / Droz, Sara / de Roche von Arx, Mirjam / Suter-Riniker, Franziska / Aujesky, Drahomir / Brugger, Silvio D

    Antimicrobial resistance and infection control

    2019  Volume 8, Page(s) 97

    Abstract: Background: Tablet computers are increasingly being used in hospital patient care and are often colonized with important human pathogens, while the impact of disinfection interventions remains controversial.: Method: In a prospective hygiene ... ...

    Abstract Background: Tablet computers are increasingly being used in hospital patient care and are often colonized with important human pathogens, while the impact of disinfection interventions remains controversial.
    Method: In a prospective hygiene intervention study we consecutively sampled tablet computers exclusively used in a high-resource general internal medicine tertiary care setting with high routine hygiene measures. Our aim was to examine the change in colonizing bacteria on tablet computers before and after the introduction of a mandatory twice daily tablet disinfection intervention. Microbial identification was performed by conventional culture, and the association of bacterial colonization with the intervention was investigated using logistic regression.
    Results: In a total of 168 samples we identified colonizing bacteria in 149 (89%) of samples. While the most commonly identified species were normal skin bacteria,
    Conclusion: Our results indicate that a twice daily disinfection can still substantially reduce bacterial colonization of in-hospital tablet computers used in a high-resource and high hygiene setting.
    MeSH term(s) Bacteria/classification ; Bacteria/drug effects ; Bacteria/isolation & purification ; Computers, Handheld ; Cross Infection/prevention & control ; Disinfection/methods ; Equipment and Supplies/microbiology ; Hand Hygiene ; Humans ; Logistic Models ; Prospective Studies ; Tertiary Healthcare
    Language English
    Publishing date 2019-06-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2666706-X
    ISSN 2047-2994 ; 2047-2994
    ISSN (online) 2047-2994
    ISSN 2047-2994
    DOI 10.1186/s13756-019-0546-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Continual hemodynamic monitoring with a single-use transesophageal echocardiography probe in critically ill patients with shock: a randomized controlled clinical trial.

    Merz, Tobias M / Cioccari, Luca / Frey, Pascal M / Bloch, Andreas / Berger, David / Zante, Bjoern / Jakob, Stephan M / Takala, Jukka

    Intensive care medicine

    2019  Volume 45, Issue 8, Page(s) 1093–1102

    Abstract: Purpose: Mortality in circulatory shock is high. Enhanced resolution of shock may improve outcomes. We aim to determine whether adding hemodynamic monitoring with continual transesophageal echocardiography (hTEE) to usual care accelerates resolution of ... ...

    Abstract Purpose: Mortality in circulatory shock is high. Enhanced resolution of shock may improve outcomes. We aim to determine whether adding hemodynamic monitoring with continual transesophageal echocardiography (hTEE) to usual care accelerates resolution of hemodynamic instability.
    Methods: 550 patients with circulatory shock were randomly assigned to four groups stratified using hTEE (hTEE vs usual care) and assessment frequency (minimum every 4 h vs 8 h). Primary outcome was time to resolution of hemodynamic instability, analyzed as intention-to-treat (ITT) analysis at day 6 and in a predefined secondary analysis at days 3 and 28.
    Results: Of 550 randomized patients, 271 with hTEE and 274 patients with usual care were eligible and included in the ITT analysis. Time to resolution of hemodynamic instability did not differ within the first 6 days [hTEE vs usual care adjusted sub-hazard ratio (SHR) 1.20, 95% confidence interval (CI) 0.98-1.46, p = 0.067]. Time to resolution of hemodynamic instability during the 72 h of hTEE monitoring was shorter in patients with TEE (hTEE vs usual care SHR 1.26, 95% CI 1.02-1.55, p = 0.034). Assessment frequency had no influence. Time to resolution of clinical signs of hypoperfusion, duration of organ support, length of stay and mortality in the intensive care unit and hospital, and mortality at 28 days did not differ between groups.
    Conclusions: In critically ill patients with shock, hTEE monitoring or hemodynamic assessment frequency did not influence resolution of hemodynamic instability or mortality within the first 6 days.
    Trial registration and statistical analysis plan: ClinicalTrials.gov Identifier: NCT02048566.
    MeSH term(s) Aged ; Critical Illness/therapy ; Echocardiography, Transesophageal/instrumentation ; Echocardiography, Transesophageal/methods ; Female ; Hemodynamic Monitoring/instrumentation ; Hemodynamic Monitoring/methods ; Humans ; Intensive Care Units/organization & administration ; Intensive Care Units/statistics & numerical data ; Logistic Models ; Male ; Middle Aged ; Proportional Hazards Models ; Shock/physiopathology ; Switzerland
    Keywords covid19
    Language English
    Publishing date 2019-07-04
    Publishing country United States
    Document type Journal Article ; Randomized Controlled Trial
    ZDB-ID 80387-x
    ISSN 1432-1238 ; 0340-0964 ; 0342-4642 ; 0935-1701
    ISSN (online) 1432-1238
    ISSN 0340-0964 ; 0342-4642 ; 0935-1701
    DOI 10.1007/s00134-019-05670-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: First Clinical Case of

    Clément, Mathieu / Keller, Peter M / Bernasconi, Odette J / Stirnimann, Guido / Frey, Pascal M / Bloemberg, Guido V / Sendi, Parham / Endimiani, Andrea

    Antimicrobial agents and chemotherapy

    2019  Volume 63, Issue 10

    Abstract: ... A pan- ... ...

    Abstract A pan-susceptible
    MeSH term(s) Cephalosporin Resistance/genetics ; Cephalosporins/pharmacology ; Citrobacter/drug effects ; Citrobacter/genetics ; Drug Resistance, Multiple, Bacterial/genetics ; Microbial Sensitivity Tests ; Plasmids/genetics ; Salmonella/drug effects ; Salmonella/genetics
    Chemical Substances Cephalosporins
    Language English
    Publishing date 2019-09-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/AAC.00992-19
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  9. Article ; Online: Correction to: Continual hemodynamic monitoring with a single-use transesophageal echocardiography probe in critically ill patients with shock: a randomized controlled clinical trial.

    Merz, Tobias M / Cioccari, Luca / Frey, Pascal M / Bloch, Andreas / Berger, David / Zante, Bjoern / Jakob, Stephan M / Takala, Jukka

    Intensive care medicine

    2019  Volume 45, Issue 9, Page(s) 1330

    Abstract: The original version of this article unfortunately contained a mistake. ...

    Abstract The original version of this article unfortunately contained a mistake.
    Language English
    Publishing date 2019-07-23
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 80387-x
    ISSN 1432-1238 ; 0340-0964 ; 0342-4642 ; 0935-1701
    ISSN (online) 1432-1238
    ISSN 0340-0964 ; 0342-4642 ; 0935-1701
    DOI 10.1007/s00134-019-05700-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Herpesvirus Reactivations in Critically-Ill COVID-19 Patients with Autoantibodies Neutralizing Type I Interferons

    Busnadiego, Idoia / Abela, Irene A / Frey, Pascal M / Hofmaenner, Daniel A / Scheier, Thomas C / Schuepbach, Reto A / Buehler, Philipp K / Brugger, Silvio D / Hale, Benjamin G

    medRxiv

    Abstract: Autoantibodies neutralizing the antiviral action of type I interferons (IFNs) have been associated with pre-disposition to severe COVID-19. Here, we screened for such autoantibodies in 103 critically-ill COVID-19 patients in a tertiary intensive care ... ...

    Abstract Autoantibodies neutralizing the antiviral action of type I interferons (IFNs) have been associated with pre-disposition to severe COVID-19. Here, we screened for such autoantibodies in 103 critically-ill COVID-19 patients in a tertiary intensive care unit in Switzerland. Eleven patients (10.7%), but no healthy donors, had neutralizing anti-IFNα or anti-IFNα/anti-IFNω IgG in plasma/serum, but anti-IFN IgM or IgA was rare. One patient had non-neutralizing anti-IFNα IgG. Strikingly, all patients with plasma anti-IFNα IgG also had anti-IFNα IgG in tracheobronchial secretions, identifying these autoantibodies at anatomical sites relevant for SARS-CoV-2 infection. Longitudinal analyses revealed patient heterogeneity in terms of increasing, decreasing, or stable anti-IFN IgG levels throughout the length of hospitalization. Notably, presence of anti-IFN autoantibodies in this critically-ill COVID-19 cohort appeared to predict herpesvirus (herpes simplex viruses types 1 and 2, HSV-1/-2; and/or cytomegalovirus, CMV) reactivations, which are linked to worse clinical outcomes. Indeed, all seven tested COVID-19 patients with anti-IFN IgG in our cohort (100%) suffered from one or more herpesvirus reactivations, and analysis revealed that these patients were substantially more likely to experience CMV reactivation than COVID-19 patients without anti-IFN autoantibodies, even when adjusting for systemic steroid treatment (odds ratio 7.28, 95%-CI 1.14-46.31, p=0.036). As the IFN system deficiency caused by neutralizing anti-IFN autoantibodies likely directly and indirectly exacerbates herpesvirus reactivations in critically-ill patients, early diagnosis of anti-IFN IgG could be rapidly used to inform risk-group stratification and treatment options.
    Keywords covid19
    Language English
    Publishing date 2022-03-21
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2022.03.19.22272532
    Database COVID19

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