Fourteen-Day Bactericidal Activity, Safety, and Pharmacokinetics of Linezolid in Adults with Drug-Sensitive Pulmonary Tuberculosis

Simple item page
dc.contributor.authorDiacon, Andreasen_ZA
dc.contributor.authorDe Jager, Veronique Ren_ZA
dc.contributor.authorDawson, Rodneyen_ZA
dc.date.accessioned2022-04-04T12:51:31Z
dc.date.available2022-04-04T12:51:31Z
dc.date.issued2020-01
dc.descriptionCITATION: Diacon AH, De Jager VR, Dawson R, Narunsky K, Vanker N, Burger DA, Everitt D, Pappas F, Nedelman J, Mendel CM. 2020. Fourteen-day bactericidal activity, safety, and pharmacokinetics of linezolid in adults with drug-sensitive pulmonary tuberculosis. Antimicrob Agents Chemother 64:e02012-19. https://doi.org/10.1128/AAC.02012-19.
dc.description.abstractBackground: Linezolid is increasingly used for the treatment of tuberculosis resistant to first-line agents, but the most effective dosing strategy is yet unknown. Methods: Between November 2014 and November 2016, we randomised 114 drug-sensitive treatment-naïve pulmonary tuberculosis patients from Cape Town, South Africa, to one of six 14-day treatment arms containing linezolid 300 mg once daily (qd), 300 mg twice daily (bd), 600 mg qd, 600 mg bd, 1200 mg qd, 1200 mg three times per week (tiw) or a combination of isoniazid, rifampicin, pyrazinamide and ethambutol. Sixteen-hour sputum samples were collected overnight, and bactericidal activity characterized by the daily percentage change in time to positivity (TTP) and colony forming units (CFU). We also assessed the safety and pharmacokinetics of the study treatments. Results: Bactericidal activity increased with increasing doses of linezolid. Based on the daily percentage change in TTP, activity was highest for 1200 mg qd (4.5; 95% Bayesian confidence interval [BCI]: 3.3-5.6), followed by 600 mg bd (4.1; BCI: 2.5-5.7), 600 mg qd (4.1; BCI: 2.9-5.3), 300 mg bd (3.3; BCI: 1.9-4.7), 300 mg qd (2.3; BCI: 1.1-3.5) and 1200 mg tiw (2.2; BCI: 1.1-3.3). Similar results were seen with bactericidal activity characterized by the daily rate of change in CFU count. Antimycobacterial activity correlated positively with plasma drug exposure and percentage time over minimum inhibitory concentration. There were no unexpected adverse events. Conclusion: All linezolid doses showed bactericidal activity. For the same total daily dose, once daily dosing proved to be at least as effective as a divided twice daily dose. An intermittent dosing regimen, with 1200 mg given three times weekly, showed the least activity.en_ZA
dc.format.extent8 pages
dc.identifier.citationdoi.org/10.1128/AAC.02012-19.
dc.identifier.otherdoi.org/10.1128/AAC.02012-19.
dc.identifier.urihttp://hdl.handle.net/10019.1/124409
dc.language.isoen_ZAen_ZA
dc.rights.holderAuthors retain copyright
dc.subjectBactericidal Activityen_ZA
dc.subjectSafetyen_ZA
dc.subjectPharmacokineticsen_ZA
dc.subjectPulmonary Tuberculosisen_ZA
dc.titleFourteen-Day Bactericidal Activity, Safety, and Pharmacokinetics of Linezolid in Adults with Drug-Sensitive Pulmonary Tuberculosisen_ZA
dc.typeArticleen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Diacon_DeJager_Dawson_et al_Fourteen-Day Bactericidal Activity Safety and Phar_2020.pdf
Size:
1.08 MB
Format:
Adobe Portable Document Format
Description:
Main Article
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Research Articles (Pulmonology)