The effect of antibiotic therapy on clinical outcome in patients hospitalized with moderate COVID-19 disease: a prospective multi-center cohort study

doi:10.1007/s15010-025-02590-0

. 2025 Jun 26.

doi: 10.1007/s15010-025-02590-0. Online ahead of print.

The effect of antibiotic therapy on clinical outcome in patients hospitalized with moderate COVID-19 disease: a prospective multi-center cohort study

Anette Friedrichs^#¹, Roman Wenz^#², Daniel Pape³, Katharina S Appel⁴, Thomas Bahmer^{3

5}, Karsten Becker⁶, Sven Bercker⁷, Sabine Blaschke⁸, Josephine Braunsteiner⁹, Jana Butzmann¹⁰, Egdar Dahl¹¹, Johanna Erber¹², Lisa Fricke¹², Ramsia Geisler⁴, Siri Göpel¹³, Andreas Güldner¹⁴, Marina Hagen¹⁵, Axel Hamprecht¹⁶, Stefan Hansch¹⁷, Peter U Heuschmann¹⁸, Sina Hopff¹⁹, Björn-Erik Ole Jensen²⁰, Nadja Käding²¹, Julia Koepsell¹⁵, Carolin E M Koll¹⁹, Marcin Krawczyk²², Thomas Lücke²³, Patrick Meybohm²⁴, Milena Milovanovic²⁵, Lazar Mitrov¹⁹, Carolin Nürnberger¹⁸, Christoph Römmele²⁶, Margarete Scherer⁴, Lena Schmidbauer¹⁸, Melanie Stecher¹⁹, Phil-Robin Tepasse²⁷, Andreas Teufel²⁸, Jörg Janne Vehreschild⁴, Christof Winter²⁹, Oliver Witzke³⁰, Christoph Wyen^{19

31}, Frank Hanses¹⁷, Amke Caliebe²

Affiliations

¹ Department of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. anette.friedrichs@uksh.de.
² Institute of Medical Informatics and Statisitics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
³ Department of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
⁴ Institute for Digital Medicine and Clinical Data Science, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
⁵ Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany.
⁶ Friedrich Loeffler-Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany.
⁷ University Hospital Leipzig, Leipzig, Germany.
⁸ Emergency Department, University Medical Center Goettingen, Göttingen, Germany.
⁹ Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁰ Institute of Medical Microbiology and Hospital Hygiene, University Hospital Magdeburg, Magdeburg, Germany.
¹¹ Institute of Pathology, University Hospital Aachen, Aachen, Germany.
¹² TUM School of Medicine, Clinical Department for Internal Medicine II, University Hospital rechts der Isar, Technical University of Munich, Munich, Germany.
¹³ Division of Infectious Diseases, Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany.
¹⁴ Department of Anesthesiology and Intensive Care Medicine, University Hospital "Carl Gustav Carus", Technische Universität Dresden, Dresden, Germany.
¹⁵ Department II of Internal Medicine, Hematology/Oncology, Goethe University, Frankfurt am Main, Germany.
¹⁶ Institute for Medical Microbiology and Virology, University Medicine Oldenburg, Oldenburg, Germany.
¹⁷ Department for Infectious Diseases and Infection Control, University Hospital Regensburg, Regensburg, Germany.
¹⁸ Institute for Clinical Epidemiology and Biometry, University of Wurzburg, Würzburg, Germany.
¹⁹ Department I for Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany.
²⁰ Department of Gastroenterology, Hepatology and Infectious Diseases, Düsseldorf University Hospital, Düsseldorf, Germany.
²¹ Infectious Diseases Clinic, University of Schleswig -Holstein, Campus Lübeck, Lübeck, Germany.
²² Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
²³ Department of Pediatrics, Ruhr University, Bochum, Germany.
²⁴ Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, Würzburg, Germany.
²⁵ Departement I of Internal Medicine, Malteser Clinic St. Franziskus Hospital, Flensburg, Germany.
²⁶ Gastroenterology and Infectious diseases, Faculty of Medicine, University Hospital of Augsburg, Augsburg, Germany.
²⁷ Department of Medicine B for Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, Münster, Germany.
²⁸ Division of Hepatology, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
²⁹ TUM School of Medicine, Institute for Clinical Chemistry and Pathobiochemistry, University Hospital rechts der Isar, Technical University of Munich, Munich, Germany.
³⁰ Department of Infectious Diseases, West German Centre of Infectious Diseases, University Medicine Essen University Hospital Essen, University Duisburg-Essen, Essen, Germany.
³¹ Praxis Ebertplatz, Cologne, Germany.

^# Contributed equally.

PMID: 40569348
DOI: 10.1007/s15010-025-02590-0

The effect of antibiotic therapy on clinical outcome in patients hospitalized with moderate COVID-19 disease: a prospective multi-center cohort study

Anette Friedrichs et al. Infection. 2025.

. 2025 Jun 26.

doi: 10.1007/s15010-025-02590-0. Online ahead of print.

Authors

Affiliations

¹ Department of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. anette.friedrichs@uksh.de.
² Institute of Medical Informatics and Statisitics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
³ Department of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
⁴ Institute for Digital Medicine and Clinical Data Science, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
⁵ Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany.
⁶ Friedrich Loeffler-Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany.
⁷ University Hospital Leipzig, Leipzig, Germany.
⁸ Emergency Department, University Medical Center Goettingen, Göttingen, Germany.
⁹ Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁰ Institute of Medical Microbiology and Hospital Hygiene, University Hospital Magdeburg, Magdeburg, Germany.
¹¹ Institute of Pathology, University Hospital Aachen, Aachen, Germany.
¹² TUM School of Medicine, Clinical Department for Internal Medicine II, University Hospital rechts der Isar, Technical University of Munich, Munich, Germany.
¹³ Division of Infectious Diseases, Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany.
¹⁴ Department of Anesthesiology and Intensive Care Medicine, University Hospital "Carl Gustav Carus", Technische Universität Dresden, Dresden, Germany.
¹⁵ Department II of Internal Medicine, Hematology/Oncology, Goethe University, Frankfurt am Main, Germany.
¹⁶ Institute for Medical Microbiology and Virology, University Medicine Oldenburg, Oldenburg, Germany.
¹⁷ Department for Infectious Diseases and Infection Control, University Hospital Regensburg, Regensburg, Germany.
¹⁸ Institute for Clinical Epidemiology and Biometry, University of Wurzburg, Würzburg, Germany.
¹⁹ Department I for Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany.
²⁰ Department of Gastroenterology, Hepatology and Infectious Diseases, Düsseldorf University Hospital, Düsseldorf, Germany.
²¹ Infectious Diseases Clinic, University of Schleswig -Holstein, Campus Lübeck, Lübeck, Germany.
²² Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
²³ Department of Pediatrics, Ruhr University, Bochum, Germany.
²⁴ Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, Würzburg, Germany.
²⁵ Departement I of Internal Medicine, Malteser Clinic St. Franziskus Hospital, Flensburg, Germany.
²⁶ Gastroenterology and Infectious diseases, Faculty of Medicine, University Hospital of Augsburg, Augsburg, Germany.
²⁷ Department of Medicine B for Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, Münster, Germany.
²⁸ Division of Hepatology, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
²⁹ TUM School of Medicine, Institute for Clinical Chemistry and Pathobiochemistry, University Hospital rechts der Isar, Technical University of Munich, Munich, Germany.
³⁰ Department of Infectious Diseases, West German Centre of Infectious Diseases, University Medicine Essen University Hospital Essen, University Duisburg-Essen, Essen, Germany.
³¹ Praxis Ebertplatz, Cologne, Germany.

^# Contributed equally.

PMID: 40569348
DOI: 10.1007/s15010-025-02590-0

Abstract

Purpose: The benefit of antibiotic treatment (ABT) for patients with moderate COVID-19 is unclear and overtreatment poses the risk of adverse effects such as Clostridioides difficile infection and antibiotic resistance. This multi-center study compares health status improvement between patients with and without ABT at hospital admission.

Methods: Between March 2020 and May 2023, hospitalized adults with confirmed SARS-CoV-2 infection were recruited from the German National Pandemic Cohort Network (NAPKON), which includes patients from various hospitals across Germany. The study population included patients with moderate or severe COVID-19 at baseline. The primary objective was to compare health improvement or decline after two weeks between patients who received ABT at baseline and those who did not in the moderate COVID-19 population. The statistical analysis adjusted for confounders such as gender, age, vaccination status, clinical condition, and comorbidities. The severe COVID-19 population was investigated as a secondary objective.

Results: A total of 1,317 patients (median age 59 years; 38% women) were eligible for analysis, of whom 1,149 had moderate and 168 severe COVID-19 disease. ABT for pneumonia was administered to 467 patients with moderate and 117 with severe COVID-19. ABT at baseline was significantly associated with a higher deterioration rate after two weeks in patients with moderate COVID-19 (ABT: 292 improvement, 61 deterioration; no ABT: 429 improvement, 14 deterioration). A similar result was obtained in the multiple regression analysis where an odds ratio of 5.00 (95% confidence interval: 2.50 - 10.93) for ABT was observed.

Conclusion: We found no benefit of antibiotic therapy in patients with moderate COVID-19. Use of ABT was associated with a higher likelihood of clinical deterioration.

Keywords: COVID-19; Clinical improvement; Clinical outcome; Moderate disease; Rational antibiotic therapy.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

References

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1. Duan Y, Ren J, Wang J, Wang S, Zhang R, Zhang H, Hu J, Deng W, Li W, Chen B. The impact of early antibiotic use on clinical outcomes of patients hospitalized with COVID-19: a propensity score-matched analysis. Infect Drug Resist. 2024. https://doi.org/10.2147/IDR.S470957 . - DOI - PubMed - PMC
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1. Garcia-Vidal C, Sanjuan G, Moreno-García E, Puerta-Alcalde P, Garcia-Pouton N, Chumbita M, Fernandez-Pittol M, Pitart C, Inciarte A, Bodro M, Morata L, Ambrosioni J, Grafia I, Meira F, Macaya I, Cardozo C, Casals C, Tellez A, Castro P, Marco F, García F, Mensa J, Martínez JA, Soriano A. Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study. Clin Microbiol Infect. 2021;27(1):83–8. https://doi.org/10.1016/j.cmi.2020.07.041 . - DOI - PubMed

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[1] Schons MJ, Caliebe A, Spinner CD, Classen AY, Pilgram L, Ruethrich MM, Rupp J, Nunes de Miranda SM, Römmele C, Vehreschild J, Jensen BE, Vehreschild M, Degenhardt C, Borgmann S, Hower M, Hanses F, Haselberger M, Friedrichs AK, LEOSS-study group. All-cause mortality and disease progression in SARS-CoV-2-infected patients with or without antibiotic therapy: an analysis of the LEOSS cohort. Infection. 2022;50(2):423–36. https://doi.org/10.1007/s15010-021-01699-2 . - DOI - PubMed

[2] Schons MJ, Caliebe A, Spinner CD, Classen AY, Pilgram L, Ruethrich MM, Rupp J, Nunes de Miranda SM, Römmele C, Vehreschild J, Jensen BE, Vehreschild M, Degenhardt C, Borgmann S, Hower M, Hanses F, Haselberger M, Friedrichs AK, LEOSS-study group. All-cause mortality and disease progression in SARS-CoV-2-infected patients with or without antibiotic therapy: an analysis of the LEOSS cohort. Infection. 2022;50(2):423–36. https://doi.org/10.1007/s15010-021-01699-2 . - DOI - PubMed

[3] Duan Y, Ren J, Wang J, Wang S, Zhang R, Zhang H, Hu J, Deng W, Li W, Chen B. The impact of early antibiotic use on clinical outcomes of patients hospitalized with COVID-19: a propensity score-matched analysis. Infect Drug Resist. 2024. https://doi.org/10.2147/IDR.S470957 . - DOI - PubMed - PMC

[4] Duan Y, Ren J, Wang J, Wang S, Zhang R, Zhang H, Hu J, Deng W, Li W, Chen B. The impact of early antibiotic use on clinical outcomes of patients hospitalized with COVID-19: a propensity score-matched analysis. Infect Drug Resist. 2024. https://doi.org/10.2147/IDR.S470957 . - DOI - PubMed - PMC

[5] Malik SS, Mundra S. Increasing consumption of antibiotics during the COVID-19 pandemic: implications for patient health and emerging anti-microbial resistance. Antibiotics. 2022;12(1): 45. https://doi.org/10.3390/antibiotics12010045 . - DOI - PubMed - PMC

[6] Malik SS, Mundra S. Increasing consumption of antibiotics during the COVID-19 pandemic: implications for patient health and emerging anti-microbial resistance. Antibiotics. 2022;12(1): 45. https://doi.org/10.3390/antibiotics12010045 . - DOI - PubMed - PMC

[7] https://register.awmf.org/assets/guidelines/113-001l_S3_Empfehlungen-zur...

[8] https://register.awmf.org/assets/guidelines/113-001l_S3_Empfehlungen-zur...

[9] Garcia-Vidal C, Sanjuan G, Moreno-García E, Puerta-Alcalde P, Garcia-Pouton N, Chumbita M, Fernandez-Pittol M, Pitart C, Inciarte A, Bodro M, Morata L, Ambrosioni J, Grafia I, Meira F, Macaya I, Cardozo C, Casals C, Tellez A, Castro P, Marco F, García F, Mensa J, Martínez JA, Soriano A. Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study. Clin Microbiol Infect. 2021;27(1):83–8. https://doi.org/10.1016/j.cmi.2020.07.041 . - DOI - PubMed

[10] Garcia-Vidal C, Sanjuan G, Moreno-García E, Puerta-Alcalde P, Garcia-Pouton N, Chumbita M, Fernandez-Pittol M, Pitart C, Inciarte A, Bodro M, Morata L, Ambrosioni J, Grafia I, Meira F, Macaya I, Cardozo C, Casals C, Tellez A, Castro P, Marco F, García F, Mensa J, Martínez JA, Soriano A. Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study. Clin Microbiol Infect. 2021;27(1):83–8. https://doi.org/10.1016/j.cmi.2020.07.041 . - DOI - PubMed

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The effect of antibiotic therapy on clinical outcome in patients hospitalized with moderate COVID-19 disease: a prospective multi-center cohort study

Affiliations

The effect of antibiotic therapy on clinical outcome in patients hospitalized with moderate COVID-19 disease: a prospective multi-center cohort study

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