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Modellierung von nosokomialen Infektionen unter Verwendung von individuellen Patientendaten

Förderung: 36 Monate, seit 2011

Beschreibung

Infektionskrankheiten in Krankenhäusern unterliegen komplexen Mechanismen, die bisher unzureichend verstanden worden sind. Um die Dynamik in der Übertragung von Krankenhauskeimen (KHK) geeignet zu modellieren, sollten folgende vier Komponten berücksichtigt werden: biologische Kenntnis der Übertragungsdynamik, epidemiologische Information auf individueller Patientenebene, demographische Kenntnis über die Krankenhauspopulation und die Einbeziehung von zeitlich variierenden Daten. Für unsere Forschung können wir auf detaillierte Patientendaten einer prospektiven Kohorte eines internationalen Netzwerkes von 537 Intensivstationen (IS) mit 119,699 Aufnahmen zugreifen. Die Daten beinhalten u.a. Informationen über verschiedene Mikroorganismen, Resistenzen, Antibiotikatherapien, tägliche Exposition zu invasiven Eingriffen und potentielle Risikofaktoren. Das Hauptziel unserer Forschung ist nun zunächst die Entwicklung eines innovativen Modelles, welches alle 4 Komponenten entsprechend einbindet. Dies erlaubt uns in den nächsten Schritten, die Wichtigkeit der vier Komponenten genau zu untersuchen und neue Einblicke in die Übertragungsdynamik zu erhalten. Dies wird direkte Auswirkungen auf potentielle Interventionen zur KHK-Prävention haben. Aufgrund der großen Kohorte können wir nicht nur epidemische Ausbrüche besser verstehen, sondern auch und vor allem endemische Situationen. Dieser Ansatz erlaubt es, Risikofaktoren über alle IS hinweg zu studieren, wobei dabei potentielle Übertragungen berücksichtigt werden. Somit können die Ergebnisse auf andere IS extrapoliert werden. Desweiteren werden verschiedene Zeitskalen und gängige Studiendesigns für Risikofaktorenanalysen (nested case-control) methodisch untersucht.

Publikationen

  • F. P. Paling, D. P. R. Troeman, M. Wolkewitz, R. Kalyani, D. R. Prins, S. Weber, C. Lammens, L. Timbermont, H. Goossens, S. Malhotra-Kumar, F. Sifakis, M. J. M. Bonten, and J. A. J. W. Kluytmans, "Rationale and design of ASPIRE-ICU: a prospective cohort study on the incidence and predictors of Staphylococcus aureus and Pseudomonas aeruginosa pneumonia in the ICU", BMC Infect. Dis., vol. 17, no. 1, Sep. 2017.
  • M. Wolkewitz, M. Zortel, M. Palomar-Martinez, F. Alvarez-Lerma, P. Olaechea-Astigarraga, and M. Schumacher, "Landmark prediction of nosocomial infection risk to disentangle short- and long-stay patients", J. Hosp. Infect., vol. 96, no. 1, pp. 81-84, May 2017.
  • M. Wolkewitz, M. von Cube, and M. Schumacher, "Multistate Modeling to Analyze Nosocomial Infection Data: An Introduction and Demonstration", Infection Control and Hospital Epidemiology, pp. 1-7, June 2017.
  • J. F. Timsit, M. E. A. de Kraker, H. Sommer, E. Weiss, E. Bettiol, M. Wolkewitz, S. Nikolakopoulos, D. Wilson, and S. Harbarth, "Appropriate endpoints for evaluation of new antibiotic therapies for severe infections: a perspective from COMBACTE's STAT-Net", Intensive Care Med, vol. 43, no. 7, pp. 1002-1012, July 2017.
  • H. Sommer, M. Wolkewitz, and M. Schumacher, "The time-dependent "cure-death" model investigating two equally important endpoints simultaneously in trials treating high-risk patients with resistant pathogens", Pharmaceutical Statistics, vol. 16, no. 4, pp. 267-279, July 2017.
  • M. von Cube, M. Schumacher, and M. Wolkewitz, "Basic parametric analysis for a multi-state model in hospital epidemiology", Bmc Medical Research Methodology, vol. 17, no. 1, July 2017.
  • F. P. Paling, M. Wolkewitz, L. G. Bode, P. M. Klein Klouwenberg, D. S. Ong, P. Depuydt, L. de Bus, F. Sifakis, M. J. Bonten, and J. A. Kluytmans, "Staphylococcus aureus colonization at ICU admission as a risk factor for developing S. aureus ICU pneumonia", Clin. Microbiol. Infect., vol. 23, no. 1, pp. 9-49, Jan. 2017.
  • T. Heister, K. Kaier, and M. Wolkewitz, "Estimating the burden of nosocomial infections: Time dependency and cost clustering should be taken into account", Am J Infect Control, vol. 45, no. 1, pp. 94-95, Jan. 2017.
  • M. von Cube, M. Schumacher, M. Palomar-Martinez, P. Olaechea-Astigarraga, F. Alvarez-Lerma, and M. Wolkewitz, "A case-cohort approach for multi-state models in hospital epidemiology", Statistics in Medicine, vol. 36, no. 3, pp. 481-495, Feb. 2017.
  • M. von Cube, M. Schumacher, M. Palomar-Martinez, P. Olaechea-Astigarraga, F. Alvarez-Lerma, and M. Wolkewitz, "A case-cohort approach for multi-state models in hospital epidemiology", Stat Med, vol. 36, no. 3, pp. 481-495, Feb. 2017.
  • Martin Wolkewitz, Gerta Rücker, and Martin Schumacher, "Changes in Rates of Ventilator-Associated Pneumonia", Jama-journal of the American Medical Association, vol. 317, no. 15, pp. 1580-1581, Apr. 2017.
  • M. Wolkewitz and M. Schumacher, "Survival biases lead to flawed conclusions in observational treatment studies of influenza patients", Journal of Clinical Epidemiology, vol. 84, pp. 121-129, Apr. 2017.
  • H. Sommer, J. F. Timsit, and M. Wolkewitz, "Bezlotoxumab and Recurrent Clostridium difficile Infection", New England Journal of Medicine, vol. 376, no. 16, 04 2017.
  • F. P. Paling, M. Wolkewitz, P. Depuydt, L. de Bus, F. Sifakis, M. J. M. Bonten, and J. A. J. W. Kluytmans, "P. aeruginosa colonization at ICU admission as a risk factor for developing P. aeruginosa ICU pneumonia", Antimicrob Resist Infect Control, vol. 6, 2017.
  • M. Wolkewitz, "Accounting for Competing Events in Multivariate Analyses of Hospital-Acquired Infection Risk Factors", Infect Control Hosp Epidemiol, vol. 37, no. 9, pp. 1122-1124, Sep. 2016.
  • M. Wolkewitz, B. S. Cooper, M. Palomar-Martinez, F. Alvarez-Lerma, P. Olaechea-Astigarraga, A. G. Barnett, and M. Schumacher, "Multiple time scales in modeling the incidence of infections acquired in intensive care units", Bmc Medical Research Methodology, vol. 16, no. 1, Sep. 2016.
  • M. Wolkewitz, B. S. Cooper, M. Palomar-Martinez, F. Alvarez-Lerma, P. Olaechea-Astigarraga, A. G. Barnett, and M. Schumacher, "Multiple time scales in modeling the incidence of infections acquired in intensive care units", BMC Med Res Methodol, vol. 16, no. 1, Sep. 2016.
  • Maja von Cube, Martin Schumacher, Mercedes Palomar-Martinez, Pedro Olaechea-Astigarraga, Francisco Alvarez-Lerma, and Martin Wolkewitz, "A case-cohort approach for multi-state models in hospital epidemiology", Statistics in Medicine, Oct. 2016.
  • S. Weber, M. von Cube, H. Sommer, and M. Wolkewitz, "Necessity of a Competing Risk Approach in Risk Factor Analysis of Central Line-Associated Bloodstream Infection", Infect Control Hosp Epidemiol, vol. 37, no. 10, pp. 1255-1257, Oct. 2016.
  • M. Wolkewitz, M. Palomar-Martinez, P. Olaechea-Astigarraga, F. Alvarez-Lerma, and M. Schumacher, "A full competing risk analysis of hospital-acquired infections can easily be performed by a case-cohort approach", Journal of Clinical Epidemiology, vol. 74, pp. 187-193, June 2016.
  • M. Dettenkofer, H. Humphreys, H. Saenz, J. Carlet, H. Hanberger, C. Ruef, A. Widmer, M. Wolkewitz, and B. Cookson, "Key priorities in the prevention and control of healthcare-associated infection: a survey of European and other international infection prevention experts", Infection, vol. 44, no. 6, pp. 719-724, Dec. 2016.
  • M. Wolkewitz, J. Beyersmann, K. Ohneberg, and M. Schumacher, "RE: "COMPARISON OF STATISTICAL APPROACHES FOR DEALING WITH IMMORTAL TIME BIAS IN DRUG EFFECTIVENESS STUDIES"", Am. J. Epidemiol., vol. 184, no. 11, pp. 856-858, 12 2016.
  • M. Wolkewitz and M. Schumacher, "Neuraminidase Inhibitors and Hospital Mortality in British Patients with H1N1 Influenza A: A Re-Analysis of Observational Data", PLoS ONE, vol. 11, no. 9, 2016.
  • M. Wolkewitz, "Estimating the Risk of Ventilator-associated Pneumonia as a Function of Time", Am. J. Respir. Crit. Care Med., vol. 192, no. 5, pp. 640-641, Sep. 2015.
  • N. Green, A. P. Johnson, K. L. Henderson, B. Muller-Pebody, S. Thelwall, J. V. Robotham, M. Sharland, M. Wolkewitz, and S. R. Deeny, "Quantifying the Burden of Hospital-Acquired Bloodstream Infection in Children in England by Estimating Excess Length of Hospital Stay and Mortality Using a Multistate Analysis of Linked, Routinely Collected Data", J Pediatric Infect Dis Soc, vol. 4, no. 4, pp. 305-312, Dec. 2015.
  • M. Wolkewitz and M. Schumacher, "Statistical and methodological concerns about the beneficial effect of neuraminidase inhibitors on mortality", Lancet Respir Med, vol. 2, no. 7, pp. 8-9, July 2014.
  • M. Wolkewitz, B. S. Cooper, M. Palomar-Martinez, P. Olaechea-Astigarraga, F. Alvarez-Lerma, and M. Schumacher, "Nested case-control studies in cohorts with competing events", Epidemiology, vol. 25, no. 1, pp. 122-125, Jan. 2014.
  • M. Wolkewitz, "Avoidable statistical pitfalls in analyzing length of stay in intensive care units or hospitals", Crit Care, vol. 18, no. 1, Feb. 2014.
  • M. Wolkewitz, A. G. Barnett, M. Palomar Martinez, U. Frank, and M. Schumacher, "Interventions to control nosocomial infections: study designs and statistical issues", J. Hosp. Infect., vol. 86, no. 2, pp. 77-82, Feb. 2014.
  • K Kaier, ML Lambert, UK Frank, W Vach W, M Wolkewitz, E Tacconelli, J Rello, U Theuretzbacher, and M Martin, "Impact of availability of guidelines and active surveillance in reducing the incidence of ventilator-associated pneumonia in Europe and worldwide", Bmc Infectious Diseases, vol. 14:199, Apr. 2014.
  • K. Kaier, M. L. Lambert, U. K. Frank, W. Vach, M. Wolkewitz, E. Tacconelli, J. Rello, U. Theuretzbacher, and M. Martin, "Impact of availability of guidelines and active surveillance in reducing the incidence of ventilator-associated pneumonia in Europe and worldwide", BMC Infect. Dis., vol. 14, Apr. 2014.
  • M. Wolkewitz, B. S. Cooper, M. Palomar-Martinez, F. Alvarez-Lerma, P. Olaechea-Astigarraga, A. G. Barnett, S. Harbarth, and M. Schumacher, "Multilevel competing risk models to evaluate the risk of nosocomial infection", Crit Care, vol. 18, no. 2, Apr. 2014.
  • M. Wolkewitz, B.S. Cooper, M. Palomar-Martinez, F. Alvarez-Lerma, P. Olaechea-Astigarraga, A.G. Barnett, S. Harbarth, and M. Schumacher, "Multilevel competing risk models to evaluate the risk of nosocomial infection", Critical Care, vol. 18, 2:R64, 2014.
  • M. Wolkewitz and H. Sommer, "Evaluating mortality in an intensive care unit requires extended survival models", Critical Care, vol. 18:415, 2014.
  • Martin Wolkewitz, "Avoidable statistical pitfalls in analyzing length of stay in intensive care units or hospitals", Critical Care, vol. 18, 1:408, 2014.
  • M. Wolkewitz, A.G. Barnett, M. Palomar Martinez, U. Frank, and M. Schumacher, "Interventions to control nosocomial infections: study designs and statistical issues", Journal of Hospital Infection, vol. 86, 2:77-82, 2014.
  • M. Wolkewitz, B.S. Cooper, M. Palomar-Martinez, P. Olaechea-Astigarraga, F. Alvarez-Lerma, and M. Schumacher, "Nested case-control studies in cohorts with competing events", Critical Care, vol. 1:122-5, 2014.
  • Martin Wolkewitz, Ben S Cooper, Marc JM Bonten, Adrian G Barnett, Martin Schumacher, and others, "Interpreting and comparing risks in the presence of competing events", BMJ, vol. 349, BMJ Publishing Group Ltd, 2014.
  • Martin Schumacher, Arthur Allignol, Jan Beyersmann, Nadine Binder, and Martin Wolkewitz, "Hospital-acquired infections-appropriate statistical treatment is urgently needed!", International Journal of Epidemiology, vol. 42, no. 5, pp. 1502-1508, Oct. 2013.
  • M. Wolkewitz, E. Tacconelli, and M. Schumacher, "Aggressive versus conservative initiation of antibiotics", Lancet Infectious Diseases, vol. 13, no. 5, pp. 387-388, May 2013.
  • M. Wolkewitz, S. Harbarth, and J. Beyersmann, "Daily chlorhexidine bathing and hospital-acquired infection", N. Engl. J. Med., vol. 368, 24:2330, 2013.
  • M. Wolkewitz, S. Di Termini, B. Cooper, J. Meerpohl, and M. Schumacher, "Paediatric hospital-acquired bacteraemia in developing countries", Lancet, vol. 379, no. 9825, pp. 1484-1485, Apr. 2012.
  • M. Wolkewitz, A. Allignol, S. Harbarth, G. de Angelis, M. Schumacher, and J. Beyersmann, "Time-dependent study entries and exposures in cohort studies can easily be sources of different and avoidable types of bias", Journal of Clinical Epidemiology, vol. 65, no. 11, pp. 1171 - 1180, 2012.
  • M. Wolkewitz, B. Cooper, A. G. Barnett, N. Binder, and M. Schumacher, "Treatment of hospital-acquired pneumonia", Lancet Infect Dis, vol. 11, no. 10, pp. 731-732, Oct. 2011.
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