Towards shortening the duration of antibiotic therapy for Lyme borreliosis: a systematic review and meta-analysis

Alice Raffetin^{1

2}, Anna J Henningsson^{3

4}, Katharina Ornstein⁵, Pauline Arias⁶, Volker Fingerle⁷, Solene Patrat-Delon⁸, Daniel Bremell^{9

10}, Per Eric Lindgren^{11

12}, Tobias A Rupprecht¹³, Benoît Jaulhac¹⁴, Klaus-Peter Hunfeld¹⁵, Céline Cazorla¹⁶, Mateusz Markowicz¹⁷, Reto Lienhard¹⁸, Alje P van Dam¹⁹, Elisabeth Baux²⁰, Sally Mavin²¹, Joppe W Hovius²², M E Baarsma²², Kristine Karlsrud Berg²³, Randi Eikeland²⁴, Ram B Dessau^{25

26}; ESGBOR the ESCMID study group for Tick-Borne Diseases

Affiliations

¹ Department of Infectious Diseases, Reference Center for Tick-Borne Diseases, Paris and Northern Region, General Hospital of Villeneuve-Saint-Georges, 40 Allée de La Source, 94190, Villeneuve-Saint-Georges, France. alice.raffetin@chiv.fr.
² DYNAMIC Research Unity, UPEC-Anses, EA7380, Créteil, France. alice.raffetin@chiv.fr.
³ Division of Clinical Microbiology, Laboratory Medicine, National Reference Laboratory for Borreliosis, Region Jönköping County, Sweden.
⁴ Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linköping University, Linköping, Sweden.
⁵ Ystad Hospital, Skåne University Healthcare, Region Skåne, Sweden.
⁶ Department of Infectious Diseases, Reference Center for Tick-Borne Diseases, Paris and Northern Region, General Hospital of Villeneuve-Saint-Georges, 40 Allée de La Source, 94190, Villeneuve-Saint-Georges, France.
⁷ National Reference Center for Borrelia, Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.
⁸ Department of Infectious Diseases, Reference Center for Tick-Borne Diseases, Western Region, University Hospital of Rennes, Rennes, France.
⁹ Institute of Biomedicine, Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden.
¹⁰ Västra Götaland Region, Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden.
¹¹ National Reference Laboratory for Borreliosis, Division of Clinical Microbiology, Laboratory Medicine, Region Jönköping County, 581 85, Jönköping, Sweden.
¹² Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, 581 85, Linköping, Sweden.
¹³ Neurology-Graefelfing, Graefelfing, Germany.
¹⁴ National Reference Center for Borrelia, Institut de Bactériologie, Fédération de Médecine Translationnelle de Strasbourg, University of Strasbourg, ITI InnoVec, UR3073-PHAVI, Strasbourg, France.
¹⁵ Institute for Laboratory Medicine, Microbiology & Infection Control, Northwest Medical Centre, Academic Teaching Hospital, Medical Faculty, Goethe University, Frankfurt, Germany.
¹⁶ Department of Infectious Diseases, Reference Center for Tick-Borne Diseases, Center Region, University Hospital of Saint-Etienne, Saint-Priest-en-Jarez, France.
¹⁷ Institute for Medical Microbiology and Hygiene, Division Public Health, AGES - Austrian Agency for Health and Food Safety, Vienna, Austria.
¹⁸ Borrelia Laboratory, National Reference Centre for Tick-Borne Disease, ADMed Microbiologie, La Chaux-de-Fonds, Switzerland.
¹⁹ Department of Medical Microbiology & the Amsterdam Institute for Immunology & Infectious Diseases, Amsterdam UMC, Amsterdam, The Netherlands.
²⁰ Department of Infectious Diseases, Reference Center for Tick-Borne Diseases, Eastern Region, University Hospital of Nancy, Nancy, France.
²¹ Scottish Lyme Disease and Tick-Borne Infections Reference Laboratory, Raigmore Hospital, Inverness, UK.
²² Department of Infectious Diseases, Center for Experimental and Molecular Medicine & the Amsterdam Institute for Immunology & Infectious Diseases, Amsterdam UMC, Amsterdam, The Netherlands.
²³ Department of Microbiology, Sørlandet Hospital Trust, Kristiansand,, Norway.
²⁴ Norwegian National Advisory Unit of Tick-Borne Diseases, Sørlandet Hospital Trust and Faculty of Health and Sport Science, University of Agder, Agder, Norway.
²⁵ Department of Clinical Microbiology, Zealand University Hospital, Slagelse, Denmark.
²⁶ Department of Clinical Health Research, University of Southern Denmark, Odense, Denmark.

PMID: 40246800
DOI: 10.1007/s15010-025-02501-3

Meta-Analysis

Towards shortening the duration of antibiotic therapy for Lyme borreliosis: a systematic review and meta-analysis

Alice Raffetin et al. Infection. 2025 Jun.

. 2025 Jun;53(3):809-830.

doi: 10.1007/s15010-025-02501-3. Epub 2025 Apr 17.

Authors

Affiliations

¹ Department of Infectious Diseases, Reference Center for Tick-Borne Diseases, Paris and Northern Region, General Hospital of Villeneuve-Saint-Georges, 40 Allée de La Source, 94190, Villeneuve-Saint-Georges, France. alice.raffetin@chiv.fr.
² DYNAMIC Research Unity, UPEC-Anses, EA7380, Créteil, France. alice.raffetin@chiv.fr.
³ Division of Clinical Microbiology, Laboratory Medicine, National Reference Laboratory for Borreliosis, Region Jönköping County, Sweden.
⁴ Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linköping University, Linköping, Sweden.
⁵ Ystad Hospital, Skåne University Healthcare, Region Skåne, Sweden.
⁶ Department of Infectious Diseases, Reference Center for Tick-Borne Diseases, Paris and Northern Region, General Hospital of Villeneuve-Saint-Georges, 40 Allée de La Source, 94190, Villeneuve-Saint-Georges, France.
⁷ National Reference Center for Borrelia, Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.
⁸ Department of Infectious Diseases, Reference Center for Tick-Borne Diseases, Western Region, University Hospital of Rennes, Rennes, France.
⁹ Institute of Biomedicine, Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden.
¹⁰ Västra Götaland Region, Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden.
¹¹ National Reference Laboratory for Borreliosis, Division of Clinical Microbiology, Laboratory Medicine, Region Jönköping County, 581 85, Jönköping, Sweden.
¹² Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, 581 85, Linköping, Sweden.
¹³ Neurology-Graefelfing, Graefelfing, Germany.
¹⁴ National Reference Center for Borrelia, Institut de Bactériologie, Fédération de Médecine Translationnelle de Strasbourg, University of Strasbourg, ITI InnoVec, UR3073-PHAVI, Strasbourg, France.
¹⁵ Institute for Laboratory Medicine, Microbiology & Infection Control, Northwest Medical Centre, Academic Teaching Hospital, Medical Faculty, Goethe University, Frankfurt, Germany.
¹⁶ Department of Infectious Diseases, Reference Center for Tick-Borne Diseases, Center Region, University Hospital of Saint-Etienne, Saint-Priest-en-Jarez, France.
¹⁷ Institute for Medical Microbiology and Hygiene, Division Public Health, AGES - Austrian Agency for Health and Food Safety, Vienna, Austria.
¹⁸ Borrelia Laboratory, National Reference Centre for Tick-Borne Disease, ADMed Microbiologie, La Chaux-de-Fonds, Switzerland.
¹⁹ Department of Medical Microbiology & the Amsterdam Institute for Immunology & Infectious Diseases, Amsterdam UMC, Amsterdam, The Netherlands.
²⁰ Department of Infectious Diseases, Reference Center for Tick-Borne Diseases, Eastern Region, University Hospital of Nancy, Nancy, France.
²¹ Scottish Lyme Disease and Tick-Borne Infections Reference Laboratory, Raigmore Hospital, Inverness, UK.
²² Department of Infectious Diseases, Center for Experimental and Molecular Medicine & the Amsterdam Institute for Immunology & Infectious Diseases, Amsterdam UMC, Amsterdam, The Netherlands.
²³ Department of Microbiology, Sørlandet Hospital Trust, Kristiansand,, Norway.
²⁴ Norwegian National Advisory Unit of Tick-Borne Diseases, Sørlandet Hospital Trust and Faculty of Health and Sport Science, University of Agder, Agder, Norway.
²⁵ Department of Clinical Microbiology, Zealand University Hospital, Slagelse, Denmark.
²⁶ Department of Clinical Health Research, University of Southern Denmark, Odense, Denmark.

PMID: 40246800
DOI: 10.1007/s15010-025-02501-3

Abstract

Objectives: Systematic review and meta-analysis on shortening antibiotic therapy for Lyme borreliosis (LB) patients.

Methods: Data sources: Medline, Google, and Google Scholar (queried from January 2022-February 2024), following the PRISMA method and the Cochrane Handbook.

Eligibility criteria: Randomized clinical trials, comparative studies; clear definitions of LB, duration of antibiotics and outcome; follow-up ≥ 6-12 months. Meta-analysis included studies that examined three outcomes: treatment failure; residual symptoms; adverse events.

Intervention: Short vs. extended antibiotic therapy for erythema migrans (≤ 10 days vs. > 10 days) and disseminated LB (≤ 21 days vs. > 21 days). Assessment of risk of bias. Independently, using the Cochrane Tools.

Methods: of data synthesis. Estimation of treatment effects based on a fixed-effect model (Mantel-Haenszel or Peto method), with odds ratio (OR) and 95% confidence intervals (CI).

Results: Thirty-eight full-text articles were examined (850 patients): 29 were included in the qualitative analysis; six in the meta-analysis. Heterogeneity was low (I² = 0%). At 12 months, short-term treatment did not differ from long-term treatment in terms of failures (OR1.50, 95%CI[0.43-5.22]) and residual symptoms (OR0.95, 95%CI[0.66-1.37]), albeit with small samples.

Conclusion: This meta-analysis was underpowered to prove non-inferiority of shorter treatment, but suggests its safety for EM. Studies focusing on antibiotics duration, with sufficient sample sizes and clear outcomes, are warranted.

Keywords: Lyme borreliosis; Meta-analysis; Outcomes; Systematic review; Treatment duration.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interests: The authors declare no competing interests regarding this paper. AR received travel reimbursement, and congress registration from Elivie, MSD and ViiV. RD & SM participated in advisory boards with Pfizer 2022 and 2024. AJH had collaborative research project with payments made to institution with Abbott laboratories, Pfizer, and Reagena Oy, unrelated to this work and with no personal remunerations. RE received travel reimbursement, congress registration, and honoraria for a lecture from Pfizer. PEL has been an external advisor to Bavarian-Nordic A/S and Pfizer Inc; and had collaborative research project with payment made to his department, with Pfizer Inc. SPD received travel reimbursement and congress registration from Pfizer (2024) and Advanz Pharma (2023). MM gave lectures for Diasorin and Mikrogen. JWH serves on advisory boards and/or has collaborative research project with payments made to his institution with Abbott laboratories, Pfizer, Moderna, Zeus Scientific, BioRad laboratories, and Tarsus. VF received financial support for NRC Borrelia from Robert Koch Institut and Bavarian Health and Food Safety Authority; lecture honoraria from Bavarian Health and Food Safety Authority, District Medical Association North Württemberg and Fenner Laboratory; travel reimbursement from QCMD, ECCMID, International Society of Dermatology in the Tropics e.V., Pfizer and BML Institut für Biomolekulare Forschung und Entwicklung. Ethical approval: Not applicable. Registration and protocol: This review had a protocol (available upon request), but it was not registered before start of the review process (January 2022). Transparency statement: The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as originally planned have been explained.

References

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Towards shortening the duration of antibiotic therapy for Lyme borreliosis: a systematic review and meta-analysis

Affiliations

Towards shortening the duration of antibiotic therapy for Lyme borreliosis: a systematic review and meta-analysis

Authors

Affiliations

Abstract

Conflict of interest statement

References

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LinkOut - more resources

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Medical