The path of anti-tuberculosis drugs: from blood to lesions to mycobacterial cells

Dartois, Véronique

doi:10.1038/nrmicro3200

Cited by 333 publications

(375 citation statements)

References 90 publications

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“…First, only 6 of 89 subjects were infected with M. tuberculosis. The pulmonary PK of INH may be altered in TB patients because of lung lesions (47). A study with a large number of TB patients would be necessary to address potential differences from healthy subjects.…”

Section: Discussionmentioning

confidence: 99%

Population Modeling and Simulation Study of the Pharmacokinetics and Antituberculosis Pharmacodynamics of Isoniazid in Lungs

Lalande

Bourguignon

Bihari

et al. 2015

Antimicrob Agents Chemother

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Among first-line antituberculosis drugs, isoniazid (INH) displays the greatest early bactericidal activity (EBA) and is key to reducing contagiousness in treated patients. The pulmonary pharmacokinetics and pharmacodynamics of INH have not been fully characterized with modeling and simulation approaches. INH concentrations measured in plasma, epithelial lining fluid, and alveolar cells for 89 patients, including fast acetylators (FAs) and slow acetylators (SAs), were modeled by use of population pharmacokinetic modeling. Then the model was used to simulate the EBA of INH in lungs and to investigate the influences of INH dose, acetylator status, and M. tuberculosis MIC on this effect. A three-compartment model adequately described INH concentrations in plasma and lungs. With an MIC of 0.0625 mg/liter, simulations showed that the mean bactericidal effect of a standard 300-mg daily dose of INH was only 11% lower for FA subjects than for SA subjects and that dose increases had little influence on the effects in either FA or SA subjects. With an MIC value of 1 mg/liter, the mean bactericidal effect associated with a 300-mg daily dose of INH in SA subjects was 41% greater than that in FA subjects. With the same MIC, increasing the daily INH dose from 300 mg to 450 mg resulted in a 22% increase in FA subjects. These results suggest that patients infected with M. tuberculosis with low-level resistance, especially FA patients, may benefit from higher INH doses, while dose adjustment for acetylator status has no significant impact on the EBA in patients with low-MIC strains.

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Section: Discussionmentioning

confidence: 99%

Population Modeling and Simulation Study of the Pharmacokinetics and Antituberculosis Pharmacodynamics of Isoniazid in Lungs

Lalande

Bourguignon

Bihari

et al. 2015

Antimicrob Agents Chemother

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“…This variety of lesions could be observed within a single individual patient simultaneously [39][40][41]. Due to their characteristic; these lesions will provide either false-positive or false-negative results on 99m Tc-ethambutol scintigraphy.…”

Section: Discussionmentioning

confidence: 99%

“…Granuloma contains predominantly intracellular M. tuberculosis with good vascularization which showed high uptake of 99m Tc-ethambutol. Negative smear sputum microscopic test in those subjects could be because granuloma did not contact with airway lung structure [39,40,44]. Subject with false positive on 99m Tc-ethambutol scintigraphy, but abnormal clinical feature and chest X-ray were considered as suggestive for active pulmonary tuberculosis.…”

Section: Discussionmentioning

confidence: 99%

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Diagnostic value of 99mTc-ethambutol scintigraphy in tuberculosis: compared to microbiological and histopathological tests

2017

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Objective Tuberculosis (TB) still remains the world's endemic infection. TB affects the lungs and any part of the body other than the lung. The diagnosis of TB has not changed much over the decades. Ethambutol is one of the first line treatments for TB. It can be labeled using 99m Tc. 99m Tc-ethambutol will be accumulated in the site of TB lesion and can be imaged using gamma camera. The aim of this study was to evaluate the diagnostic value of 99m Tc-ethambutol scintigraphy in detecting and localizing of TB. Methods Retrospective cross-sectional study was done. Subjects were patients suspected of having TB infection. Whole body and SPECT-CT imaging at the suspected area was done 1 and 4 h after injection of 370-555 MBq 99m Tc-ethambutol scintigraphy was analyzed visually. The results were compared with that of histopathological or microbiological tests. Statistical analysis was done to determine the sensitivity, specificity, PPV, NPV and accuracy. Results One hundred and sixty-eight subjects were involved in this study. There were 110 men and 58 women with mean age of 34.52 ± 11.94 years. There were concordance results in 156 (92.86%) and discordant in 12 (7.14%) subjects between 99m Tc-ethambutol scintigraphy and histopathological or microbiological result. The sensitivity, specificity, PPV, NPV and accuracy of 99m Tc-ethambutol scintigraphy in the diagnosis of pulmonary TB were 93.9, 85.7, 93.9, 85.7 and 91.4%, respectively, 77.8, 97.9, 63.6, and 85.1%, respectively, and for total tuberculosis 94.9, 83.3, 96.3, 78.1 and 92.8%, respectively. There was no side effect observed in this study. Conclusion 99m Tc-ethambutol scintigraphy is a useful diagnostic imaging technique to detect and localize intra-and extrapulmonary TB. It is safe to be performed even in pediatric patient. Consuming ethambutol less than 2 weeks did not influence the result.

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“…The major TB drug RIF diffuses efficiently into caseous regions, while PZA is distributed equally well in cellular and caseous regions [73]. These findings warrant evaluation of drug distribution and kinetics of accumulation in TB lesions for future drug development [396].…”

Section: Clinical Implications Of Dormancy and Persistencementioning

confidence: 99%

Interplay of human macrophages and Mycobacterium tuberculosis phenotypes

Raffetseder¹

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The path of anti-tuberculosis drugs: from blood to lesions to mycobacterial cells

Cited by 333 publications

References 90 publications

Population Modeling and Simulation Study of the Pharmacokinetics and Antituberculosis Pharmacodynamics of Isoniazid in Lungs

Population Modeling and Simulation Study of the Pharmacokinetics and Antituberculosis Pharmacodynamics of Isoniazid in Lungs

Diagnostic value of 99mTc-ethambutol scintigraphy in tuberculosis: compared to microbiological and histopathological tests

Interplay of human macrophages and Mycobacterium tuberculosis phenotypes

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