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Original Investigation
November 2018

Efficacy and Safety of Antibiotic Therapy in Early Cutaneous Lyme Borreliosis: A Network Meta-analysis

Author Affiliations
  • 1Institute for Evidence in Medicine (for Cochrane Germany Foundation), Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  • 2Department of Dermatology and Allergology, Technical University of Munich, München, Germany
  • 3Division of General Practice and Family Medicine, Department of Health Services Research, University of Oldenburg, Oldenburg, Germany
  • 4Department of Neurology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
  • 5National Reference Centre for Borrelia, Bavarian Health and Food Safety Authority, Oberschleißheim, Germany
  • 6Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
JAMA Dermatol. 2018;154(11):1292-1303. doi:10.1001/jamadermatol.2018.3186
Key Points

Question  What are the most effective and safest antibiotic treatments of early cutaneous Lyme borreliosis?

Findings  This network meta-analysis that included 2532 patients did not detect any significant differences in treatment response by antibiotic agent, dose, or duration. There were also no differences in the effect sizes among antibiotic agents and treatment modalities in treatment-related adverse outcomes, which were generally mild to moderate, and treatment failures were rare.

Meaning  Neither the antibiotic agent nor the treatment modality contributes to comparative effectiveness or drug-related adverse outcomes in early cutaneous Lyme borreliosis.

Abstract

Importance  Controversies about the choice of antibiotic agent and treatment modality exist in the management of erythema migrans in early cutaneous Lyme borreliosis (LB).

Objective  To conduct a network meta-analysis (NMA) of all randomized clinical trials on various antibiotic agents and treatment modalities in early cutaneous LB.

Data Sources  Electronic searches in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were conducted from inception until July 2017. The reference lists of the included studies were hand searched, authors were contacted, and ongoing trials were searched at ClinicalTrials.gov.

Study Selection  One reviewer screened the titles and abstracts of the 9975 reports identified by the electronic searches. Full-text copies of 161 potentially relevant articles were obtained, and 2 reviewers independently assessed those articles for inclusion. Adults with a physician-confirmed early localized skin infection who were treated with antibiotics of any dose or duration were included.

Data Extraction and Synthesis  Two reviewers independently extracted data on study, patient, and intervention characteristics. Network meta-analyses on treatment effects and adverse outcomes were calculated with a frequentist approach using the R package netmeta. The Grading of Recommendations Assessment, Development and Evaluation guidance for NMA was used to assess the certainty of evidence.

Main Outcomes and Measures  Treatment effects for response to treatment (resolution of symptoms) and treatment-related adverse events.

Results  Overall, 19 studies (2532 patients) were included. The mean patient age ranged between 37 and 56 years, and the percentage of female patients ranged from 36% to 60%. The antibiotics investigated were doxycycline, cefuroxime axetil, ceftriaxone, amoxicillin, azithromycin, penicillin V, and minocycline. Pooled effect sizes from NMAs did not suggest any significant differences in treatment response by antibiotic agent (eg, amoxicillin vs doxycycline odds ratio, 1.26; 95% CI, 0.41-3.87), dose, or duration (eg, doxycycline, 200 mg/d for 3 weeks, vs doxycycline, 200 mg/d for 2 weeks, odds ratio, 1.28; 95% CI, 0.49-3.34). Treatment failures were rare at both 2 months (4%; 95% CI, 2%-5%) and 12 months (2%, 95% CI, 1%-3%) after treatment initiation. There were also no differences in the effect sizes among antibiotic agents and treatment modalities for treatment-related adverse outcomes, which were generally mild to moderate. Certainty of evidence was categorized as low and very low mostly because of imprecision, indirectness, and study limitations (high risk of bias) of the included studies.

Conclusions and Relevance  This NMA suggests that neither the antibiotic agent nor treatment modality contributed to comparative effectiveness or drug-related adverse outcomes. This finding is relevant for physicians treating patients with LB and for patient decision making.

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