title: Efficacy and safety of pharmacological treatments for acute Lyme neuroborreliosis - a systematic review.
abstract: OBJECTIVE
  Our aim was to evaluate the available evidence for pharmacological treatment of acute Lyme neuroborreliosis as a basis for evidence-based clinical recommendations in a systematic review.
  
  
  METHODS
  A systematic literature search of Medline, EMBASE, the Cochrane Library and three trial registries was performed. Randomized controlled trials (RCTs) and non-randomized studies (NRS) were evaluated. Risk of bias was assessed using the Cochrane risk of bias tools. The primary outcome was 'residual neurological symptoms' whilst the secondary outcomes were disability, quality of life, pain, fatigue, depression, cognition, sleep, adverse events and cerebrospinal fluid pleocytosis. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
  
  
  RESULTS
  After screening 5779 records, eight RCTs and eight NRS were included. Risk of bias was generally high. No statistically significant difference was found between doxycycline and beta-lactam antibiotics in a meta-analysis regarding residual neurological symptoms at 4-12 months [risk ratio (RR) 1.27, 95% confidence interval (CI) 0.98-1.63, P = 0.07] or adverse events (RR 0.82, 95% CI 0.54-1.25, P = 0.35). Significantly fewer neurological symptoms for cefotaxime compared with penicillin were found (RR 1.81, 95% CI 1.10-2.97, P = 0.02). Adverse events were significantly fewer for penicillin (RR 0.56, 95% CI 0.38-0.84, P = 0.005).
  
  
  CONCLUSIONS
  Evidence regarding pharmacological treatment of acute Lyme neuroborreliosis is scarce and therefore insufficient to recommend preference of beta-lactam antibiotics over doxycycline or vice versa. However, due to considerable imprecision, relevant differences between treatments cannot be excluded. No evidence suggesting benefits of extended antibiotic treatments could be identified. Further well-designed trials are needed. Individual treatment decisions should address patients' preferences and individual conditions like prior allergic reactions.
authors.affiliation: German Cochrane Centre, Medical Center - University of Freiburg, Freiburg, Germany.|Department of Neurology, Medical Center - University of Freiburg, Freiburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Dersch
authors.affiliation: Division of General Practice, Department of Health Services Research, Carl von Ossietzky University Oldenburg, Oldenburg, Germany.
authors.forename: M H
authors.initials: MH
authors.lastname: Freitag
authors.affiliation: German Cochrane Centre, Medical Center - University of Freiburg, Freiburg, Germany.|UroEvidence@Deutsche Gesellschaft für Urologie, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: German Cochrane Centre, Medical Center - University of Freiburg, Freiburg, Germany.|Institute of Medical Biometry and Statistics, Medical Center - University of Freiburg, Freiburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Sommer
authors.affiliation: Department of Neurology, Medical Center - University of Freiburg, Freiburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Rauer
authors.affiliation: German Cochrane Centre, Medical Center - University of Freiburg, Freiburg, Germany.
authors.forename: J J
authors.initials: JJ
authors.lastname: Meerpohl
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002439:Cefotaxime / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004318:Doxycycline / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020852:Lyme Neuroborreliosis / Q000188:drug therapy*; D010406:Penicillins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D047090:beta-Lactams / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D010406:Penicillins; D047090:beta-Lactams; D004318:Doxycycline; D002439:Cefotaxime
keywords: Lyme disease; Lyme neuroborreliosis; decision making; drug treatment; meta-analysis; non-randomized studies; randomized controlled trials; systematic review