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The CLEAR regimen (Concomitant Levofloxacin, Ethambutol, Azithromycin, and Rifampin) is an investigational antimycobacterial antibiotic combination therapy developed by Vanderbilt University for the treatment of chronic cutaneous and pulmonary sarcoidosis. The regimen consists of four small molecule antibiotics administered concomitantly: levofloxacin (a fluoroquinolone targeting DNA gyrase A), ethambutol (targeting arabinosyltransferase B for cell wall synthesis), azithromycin (a macrolide targeting the 50S ribosomal subunit for protein synthesis), and rifampin (targeting RNA polymerase). The therapy is based on the hypothesis that mycobacterial antigens play a role in sarcoidosis pathogenesis. In randomized, placebo-controlled trials, the CLEAR regimen demonstrated significant reductions in chronic cutaneous sarcoidosis lesion diameter and severity, as well as improvements in pulmonary function including forced vital capacity (FVC) and 6-minute walk distance in patients with chronic pulmonary sarcoidosis.
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