Fourteen-day PET/CT imaging to monitor drug combination activity in treated individuals with tuberculosis
| Autor: | Keith Lumbard, Stephanus T. Malherbe, Taeksun Song, Gerhard Walzl, Dean Follmann, Jing Wang, Andre G. Loxton, Clifton E. Barry, Ying Cai, Praveen Paripati, Naadira Vanker, Lisa C. Goldfeder, Yingda L. Xie, Veronique R. de Jager, Saher Lahouar, Laura E. Via, Ray Y. Chen, Jill Winter, Lori E. Dodd, Andreas H. Diacon, Xiang Yu, Kriti Arora, Jenna Andrews, Michael Duvenhage |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Tuberculosis 030106 microbiology Antitubercular Agents 03 medical and health sciences 0302 clinical medicine Moxifloxacin Fluorodeoxyglucose F18 Positron Emission Tomography Computed Tomography medicine Humans 030212 general & internal medicine Tuberculosis Pulmonary Experimental drug medicine.diagnostic_test business.industry General Medicine Pyrazinamide medicine.disease Drug Combinations Positron emission tomography Sputum Drug Therapy Combination Radiology medicine.symptom business Rifampicin Combination drug medicine.drug |
| Zdroj: | Science translational medicine. 13(579) |
| ISSN: | 1946-6242 |
| Popis: | Early bactericidal activity studies monitor daily sputum bacterial counts in individuals with tuberculosis (TB) for 14 days during experimental drug treatment. The rate of change in sputum bacterial load over time provides an informative, but imperfect, estimate of drug activity and is considered a critical step in development of new TB drugs. In this clinical study, 160 participants with TB received isoniazid, pyrazinamide, or rifampicin, components of first-line chemotherapy, and moxifloxacin individually and in combination. In addition to standard bacterial enumeration in sputum, participants underwent 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography and computerized tomography ([18F]FDG-PET/CT) at the beginning and end of the 14-day drug treatment. Quantitating radiological responses to drug treatment provided comparative single and combination drug activity measures across lung lesion types that correlated more closely with established clinical outcomes when combined with sputum enumeration compared to sputum enumeration alone. Rifampicin and rifampicin-containing drug combinations were most effective in reducing both lung lesion volume measured by CT imaging and lesion-associated inflammation measured by PET imaging. Moxifloxacin was not superior to rifampicin in any measure by PET/CT imaging, consistent with its performance in recent phase 3 clinical trials. PET/CT imaging revealed synergy between isoniazid and pyrazinamide and demonstrated that the activity of pyrazinamide was limited to lung lesion, showing the highest FDG uptake during the first 2 weeks of drug treatment. [18F]FDG-PET/CT imaging may be useful for measuring the activity of single drugs and drug combinations during evaluation of potential new TB drug regimens before phase 3 trials. |
| Databáze: | OpenAIRE |
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