Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis
| Autor: | Irina Sabulua, Brent P. Little, Sergo Vashakidze, Russell R. Kempker, M. Tobias Heinrichs, Nino Bablishvili, Henry M. Blumberg, Shota Gogishvili, Nestani Tukvadze, Charles A. Peloquin, Zaza Avaliani, Hartmut Derendorf, Timothy D. Read, Adam Bernheim, Jeannette Guarner, Ketino Nikolaishvili |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Necrosis Tuberculosis 030106 microbiology Gastroenterology Mycobacterium tuberculosis 03 medical and health sciences Internal medicine medicine Pharmacology (medical) Pharmacology Lung biology business.industry Isoniazid Pyrazinamide biology.organism_classification medicine.disease Infectious Diseases medicine.anatomical_structure Histopathology medicine.symptom business Ex vivo medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 61 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.00226-17 |
| Popis: | Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary ( n = 6 patients), mass-like ( n = 3 patients), or consolidative ( n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis ( R = −0.66, P = 0.04) and acid-fast bacilli ( R = −0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. |
| Databáze: | OpenAIRE |
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