Measurement of Anti-TB Drugs in Lung Tissue From Patients Having Surgery to Treat Tuberculosis

Summary

This study, conducted jointly by researchers at the National Masan TB Hospital, Asan and Samsung Medical Centers in Seoul, Republic of Korea, and the Yonsei University and the NIH in the United States, will examine why some patients with tuberculosis (TB) develop disease that is harder to treat than most cases. TB is an infection of the lung that usually can be successfully treated with anti-TB drugs. However, some people get a more serious kind of disease (called multi-drug resistant TB or extensively drug-resistant TB) that is very difficult to treat and may not be cured by the regular medicines available. This study will try to find out if some of the common TB drugs are getting to the place where the TB bacteria are. It will also look at how current anti-TB drugs might be used more effectively and how better drugs might be developed. People 20 years of age and older with hard-to-treat TB who have elected to undergo surgical removal of part of their lung at the National Masan Tuberculosis Hospital, Masan, the Asan Medical Center, and the Samsung Medical Center, may be eligible for this study. Participants undergo the following procedures: * Medical history and physical examination, including sputum sample. * Blood tests at various times during the study. * Drug administration. Subjects are given one dose each of five common TB drugs rifampicin, isoniazid, pyrazinamide, kanamycin and moxifloxacin before they undergo surgery to remove part of their lung. After surgery, some of the lung tissue and fluid around the lungs that was removed during surgery will be examined to determine the regions where the TB bacteria live and analyze the lung tissue itself. * Dynamic MRI (magnetic resonance imaging) scan. This type of scan uses a magnetic field and radio waves to produce pictures of the lung. Subjects lie very still on a table inside the cylindrical scanner with their head on a soft cradle and their hands over their head. Several images are obtained for less than 5 minutes at a time.

Timeline

Start

2008-12-29

Primary completion

2014-08-26

Completion

2017-12-29

Publications

• Background Soman A, Honeybourne D, Andrews J, Jevons G, Wise R. Concentrations of moxifloxacin in serum and pulmonary compartments following a single 400 mg oral dose in patients undergoing fibre-optic bronchoscopy. J Antimicrob Chemother. 1999 Dec;44(6):835-8. doi: 10.1093/jac/44.6.835.
• Background Drexler DM, Garrett TJ, Cantone JL, Diters RW, Mitroka JG, Prieto Conaway MC, Adams SP, Yost RA, Sanders M. Utility of imaging mass spectrometry (IMS) by matrix-assisted laser desorption ionization (MALDI) on an ion trap mass spectrometer in the analysis of drugs and metabolites in biological tissues. J Pharmacol Toxicol Methods. 2007 May-Jun;55(3):279-88. doi: 10.1016/j.vascn.2006.11.004. Epub 2006 Dec 5.
• Background Wagner C, Sauermann R, Joukhadar C. Principles of antibiotic penetration into abscess fluid. Pharmacology. 2006;78(1):1-10. doi: 10.1159/000094668. Epub 2006 Jul 19.
• Strydom N, Gupta SV, Fox WS, Via LE, Bang H, Lee M, Eum S, Shim T, Barry CE 3rd, Zimmerman M, Dartois V, Savic RM. Tuberculosis drugs' distribution and emergence of resistance in patient's lung lesions: A mechanistic model and tool for regimen and dose optimization. PLoS Med. 2019 Apr 2;16(4):e1002773. doi: 10.1371/journal.pmed.1002773. eCollection 2019 Apr.

Drugs

Indications