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Vancomycin is active in vitro and in vivo in mouse systems against Lyme disease borrelia; however, there are no published data on the efficacy of vancomycin in patients with Lyme disease and no convincing theoretical advantages of vancomycin over the currently used and highly effective orally administered antimicrobial agents, including doxycycline, amoxicillin and cefuroxime axetil. In addition, vancomycin may cause a wide variety of potentially serious adverse effects and requires the placement of an intravenous catheter. It is concluded that vancomycin is a much less attractive option for the treatment of patients with early Lyme disease (or any other manifestation of Lyme disease), compared with the antimicrobials currently being used. Based on available evidence, clinical studies to evaluate the safety and efficacy of vancomycin for Lyme disease cannot be recommended.