Rainer König1,2,3, Xueqi Cao1,2,3, Marcus Oswald1,2,3, Christina Forstner4,5, Gernot Rohde6,7,8, Jan Rupp7,9, Martin Witzenrath7,10, Tobias Welte7,11, Martin Kolditz12, Mathias Pletz13,7. 1. Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany. 2. Network Modelling, Hans Knöll Institut Jena, Jena, Germany. 3. These authors contributed equally. 4. Institute of Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany. 5. Dept of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria. 6. Dept of Respiratory Medicine, Medical Clinic I, Goethe University Hospital, Frankfurt/Main, Germany. 7. CAPNETZ STIFTUNG, Hannover Medical School, Hannover, Germany. 8. Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL). 9. Dept of Infectious Diseases and Microbiology, University-Hospital Schleswig-Holstein/Campus Lübeck, University of Lübeck, Lübeck, Germany. 10. Division of Pulmonary Inflammation, and Dept of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 11. Dept of Respiratory Medicine, Hannover Medical School, Hannover, Germany. 12. Division of Pulmonology, Medical Dept I, University Hospital Carl Gustav Carus, Dresden, Germany. 13. Institute of Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany mathias.pletz@med.uni-jena.de.
Abstract
BACKGROUND: The role of macrolide/β-lactam combination therapy in community-acquired pneumonia (CAP) of moderate severity is a matter of debate. Macrolides expand the coverage to atypical pathogens and attenuate pulmonary inflammation, but have been associated with cardiovascular toxicity and drug interactions. We developed a decision tree based on aetiological and clinical parameters, which are available ex ante to support a personalised decision for or against macrolides for the best clinical outcome of the individual patient. METHODS: We employed machine learning in a cross-validation scheme based on a well-balanced selection of 4898 patients after propensity score matching to data available on admission of 6440 hospitalised patients with moderate severity (non-intensive care unit patients) from the observational, prospective, multinational CAPNETZ study. We aimed to improve the primary outcome of 180-day survival. RESULTS: We found a simple decision tree of patient characteristics comprising chronic cardiovascular and chronic respiratory comorbidities as well as leukocyte counts in the respiratory secretion at enrolment. Specifically, we found that patients without cardiovascular or patients with respiratory comorbidities and high leukocyte counts in the respiratory secretion benefit from macrolide treatment. Patients identified to be treated in compliance with our treatment suggestion had a lower mortality of 27% (OR 1.83, 95% CI 1.48-2.27; p<0.001) compared to the observed standard of care. CONCLUSION: Stratifying macrolide treatment in patients following a simple treatment rule may lead to considerably reduced mortality in CAP. A future randomised controlled trial confirming our result is necessary before implementing this rule into the clinical routine.
BACKGROUND: The role of macrolide/β-lactam combination therapy in community-acquired pneumonia (CAP) of moderate severity is a matter of debate. Macrolides expand the coverage to atypical pathogens and attenuate pulmonary inflammation, but have been associated with cardiovascular toxicity and drug interactions. We developed a decision tree based on aetiological and clinical parameters, which are available ex ante to support a personalised decision for or against macrolides for the best clinical outcome of the individual patient. METHODS: We employed machine learning in a cross-validation scheme based on a well-balanced selection of 4898 patients after propensity score matching to data available on admission of 6440 hospitalised patients with moderate severity (non-intensive care unit patients) from the observational, prospective, multinational CAPNETZ study. We aimed to improve the primary outcome of 180-day survival. RESULTS: We found a simple decision tree of patient characteristics comprising chronic cardiovascular and chronic respiratory comorbidities as well as leukocyte counts in the respiratory secretion at enrolment. Specifically, we found that patients without cardiovascular or patients with respiratory comorbidities and high leukocyte counts in the respiratory secretion benefit from macrolide treatment. Patients identified to be treated in compliance with our treatment suggestion had a lower mortality of 27% (OR 1.83, 95% CI 1.48-2.27; p<0.001) compared to the observed standard of care. CONCLUSION: Stratifying macrolide treatment in patients following a simple treatment rule may lead to considerably reduced mortality in CAP. A future randomised controlled trial confirming our result is necessary before implementing this rule into the clinical routine.
Authors: Tom D Y Reijnders; Hessel Peters-Sengers; Lonneke A van Vught; Fabrice Uhel; Marc J M Bonten; Olaf L Cremer; Marcus J Schultz; Martijn M Stuiver; Tom van der Poll Journal: Crit Care Date: 2022-05-24 Impact factor: 19.334
Authors: Mathias W Pletz; Andreas Vestergaard Jensen; Christina Bahrs; Claudia Davenport; Jan Rupp; Martin Witzenrath; Grit Barten-Neiner; Martin Kolditz; Sabine Dettmer; James D Chalmers; Daiana Stolz; Norbert Suttorp; Stefano Aliberti; Wolfgang M Kuebler; Gernot Rohde Journal: Respir Res Date: 2022-09-10