Activity of linezolid-containing regimens against multidrug-resistant tuberculosis in mice |
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| Affiliation: | 1. Department of Pharmacology, Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China;2. Pharmacy of Beijing Chest Hospital affiliated to The Capital Medical University, Beijing, China;1. Burns Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia;2. Royal Brisbane and Women''s Hospital, Queensland, Australia;1. INSERM U914 ‘Emerging Resistance to Antibiotics’, K.-Bicêtre, France;2. Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland;3. International Center for Medical Research and Training, CIDEIM, Cali, Colombia;1. 1st Division of Infectious Diseases, ‘Luigi Sacco’ Hospital, via GB Grassi 74, Milan 20157, Italy;2. Division of Infectious Diseases, ‘Careggi’ Hospital, Florence, Italy;3. Infectious Diseases Clinic, ‘San Martino’ Hospital, Genoa, Italy;4. Infectious Diseases Clinic, ‘Santa Maria Annunziata’ Hospital, Florence, Italy;5. 3rd Division of Infectious Diseases, Istituto Nazionale di Malattie Infettive ‘Lazzaro Spallanzani’, Rome, Italy;6. Division of Infectious Diseases, ‘Ospedale di Circolo’, Busto Arsizio, Italy;7. Division of Infectious Diseases, ‘Santa Maria della Misericordia’ Hospital, Perugia, Italy;8. Infectious Diseases Clinic, ‘Luigi Sacco’ Hospital, Milan, Italy;9. Infectious Diseases Clinic, ‘San Gerardo de’ Tintori’ Hospital, Monza, Italy;10. Infectious Diseases Clinic, Azienda Ospedaliera Universitaria Policlinico, Modena, Italy;11. Division of Infectious Diseases, ‘Santa Maria della Misericordia’ Hospital, Rovigo, Italy;12. Division of Infectious Diseases, ‘Policlinico G. Martino’, Messina, Italy;13. Division of Infectious Diseases, ‘Santo Spirito’ Hospital, Pescara, Italy;14. Division of Infectious Diseases, ‘Santa Maria della Misericordia’ Hospital, Grosseto, Italy;15. Infectious Diseases Unit, University of Catania, ARNAS Garibaldi, Catania, Italy;p. 2nd Division of Internal Medicine, Azienda Ospedaliera di Desio e Vimercate Hospital, Vimercate, Italy;1. Communicable Disease Center, Institute of Infectious Diseases and Epidemiology, Department of Infectious Disease, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore;2. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228, Singapore |
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| Abstract: | The objective of the present study was to compare the activities of regimens containing linezolid (LZD) with those not containing LZD against Mycobacterium tuberculosis infection in mice. The three regimens excluding LZD selected in this study are often used in practice against multidrug-resistant tuberculosis (MDR-TB). When LZD was added to these MDR-TB regimens, the combinations were significantly more active after 2 months of therapy with regard to lung CFU reductions. The activity of LZD-containing regimens was greater than the World Health Organization's standard first-line regimen of rifampicin + isoniazid + pyrazinamide. In particular, when LZD was included in the combination levofloxacin + amikacin + para-aminosalicylic acid + pyrazinamide + clofazimine, culture negativity of the lungs was reached after 2 months of treatment in every case. In addition, the serum levels of interleukin-10 and interferon-γ of mice were determined and were found not to be surrogate markers of bacterial clearance. |
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| Keywords: | Linezolid Combination regimen Multidrug-resistant tuberculosis Extensively drug-resistant tuberculosis Activity Cytokine |
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