Therapeutic drug monitoring of isoniazid and rifampicin during anti-tuberculosis treatment in Auckland, New Zealand

Maze, Michael J.; Paynter, Jennifer A.; Chiu, Weldon; Hu, Rong; Nisbet, Mitzi; Lewis, Clinton

doi:10.5588/ijtld.15.0792

Cited by 9 publications

(5 citation statements)

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“…Barriers to TDM implementation are highlighted in a recent meta-analysis that aimed to summarize the evidence for the use of TDM but found generally low-quality observational studies from a few specialized centers [ 27 ]. Still other individual studies from well-resourced settings which have concluded that TDM did not affect outcome have examined its use only after patients have manifested slow response to therapy where equivalence in outcome could instead be interpreted as an actual benefit conferred by TDM in preventing the more rare events of relapse or acquired drug resistance [ 28 ]. In contrast in Virginia, recommendations were made to use TDM systematically early in the treatment course prior to the development of slow response for a distinct subpopulation at higher risk of poor treatment outcome.…”

Section: Discussionmentioning

confidence: 99%

Early interventions for diabetes related tuberculosis associate with hastened sputum microbiological clearance in Virginia, USA

et al. 2017

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BackgroundDiabetes complicates tuberculosis (TB) treatment including a prolonged time of sputum culture conversion to negative growth. Since 2013 in Virginia, interventions early in the treatment course have used therapeutic drug monitoring and dose correction for isoniazid and rifampin after 2 weeks of TB treatment in patients with diabetes along with nurse manager initiated diabetes education and linkage to care.MethodsA retrospective cohort study of the state TB registry was performed for patients initiating drug-susceptible pulmonary TB treatment that were matched for age, gender, chest imaging and sputum smear status to compare time to sputum culture conversion and other clinical outcomes in the pre-and post-intervention groups.ResultsThree hundred sixty-three patients had documented time to sputum culture conversion in the pre-and post-intervention periods, including 56 (15%) with diabetes. Seventy-four (57%) of all patients with diabetes were ≥60 years of age at treatment initiation. Twenty-six patients with diabetes were matched in each group. Mean time to sputum culture conversion in the post-intervention group was 42 ± 22 days compared to the pre-intervention group of 62 ± 31 days (p = 0.01). In the post-intervention group 21 (80%) of patients with diabetes had culture conversion by 2 months compared to 13 (50%) in the pre-intervention group (p = 0.04).ConclusionsEarly interventions for diabetes related TB in the programmatic setting may hasten sputum culture conversion.

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Section: Discussionmentioning

confidence: 99%

Early interventions for diabetes related tuberculosis associate with hastened sputum microbiological clearance in Virginia, USA

et al. 2017

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“…A recent report by Maze et al from New Zealand observed that even though patients had drug concentrations below the international therapeutic ranges, they were successfully treated (35). This raises a pertinent question: is there a need to define cutoff drug concentrations in various settings that would be a predictive marker of an unfavorable outcome?…”

Section: Discussionmentioning

confidence: 99%

Factors Influencing Tuberculosis Treatment Outcome in Adult Patients Treated with Thrice-Weekly Regimens in India

Ramachandran

Kupparam

Chandrasekaran

et al. 2017

Antimicrob Agents Chemother

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The Indian Revised National Tuberculosis (TB) Control Programme uses thrice-weekly treatment with standard drug dosages. The role of plasma drug levels and other factors in determining TB treatment outcomes is not well understood. We aimed to determine the factors influencing the concentrations of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) at 2 h postdosing in adult TB patients and to study the factors impacting TB treatment outcome. We recruited 1,912 adult TB patients (newly treated and retreated patients) with pulmonary/extrapulmonary TB receiving antitubercular treatment (ATT) in the RNTCP in Chennai, India. At steady state, the concentrations of RMP, INH, and PZA were determined at 2 h postdosing after supervised drug administration. A total of 1,648 patients had a favorable outcome, while 264 (14%) had an unfavorable outcome. A total of 91%, 16%, and 17% of the patients had suboptimal concentrations of RMP (Ͻ8 g/ml), INH (Ͻ3 g/ml), and PZA (Ͻ20 g/ml), respectively. Factors associated with treatment outcome were low RMP concentrations (adjusted odds ratio [aOR], 0.94; 95% confidence interval [CI], 0.89 to 0.99; P ϭ 0.036), category II ATT (aOR, 2.39; 95% CI, 1.56 to 3.65; P Ͻ 0.001), low body weight (aOR, 0.96; 95% CI, 0.94 to 0.98; P Ͻ 0.001), alcohol use (aOR, 2.17; 95% CI, 1.42 to 3.31; P Ͻ 0.001), male gender (aOR, 1.92; 95% CI, 1.02 to 3.62; P ϭ 0.043), and baseline INH resistance (aOR, 5.74; 95% CI, 3.12 to 10.59; P Ͻ 0.001), which significantly increased the likelihood of an unfavorable outcome in multivariate logistic regression analysis. Further studies are needed to optimize anti-TB drug dosages and improve cure rates. Drug susceptibility testing at the baseline and attention to undernutrition and alcohol dependence are other important interventions.

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“…Although the World Health Organization (WHO) has published guidelines for the treatment of TB with dose recommendations based on body weight, drug exposure may differ significantly in individuals due to pharmacokinetic (PK) variability 3–7 . Suboptimal drug exposure has been extensively reported to be associated with unfavourable outcomes such as delayed sputum conversion, treatment failure and even the development of drug resistance 8–10 …”

Section: Introductionmentioning

confidence: 99%

Drug exposure of first‐line anti‐tuberculosis drugs in China: A prospective pharmacological cohort study

Forsman

Ren

Zheng

et al. 2020

Brit J Clinical Pharma

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Aim Exploring the need for optimization of drug exposure to improve tuberculosis (TB) treatment outcome is of great importance. We aimed to describe drug exposure at steady state as well as the population pharmacokinetics (PK) of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) in Chinese TB patients. Methods A prospective multicentre PK study of RIF, INH and PZA was conducted in China between January 2015 and December 2017. Six blood samples were collected from each subject for drug concentration measurement. Nonlinear mixed effect analyses were used to develop population PK models. Results In total, 217 patients were included. Positive correlations between body weight, clearance and volume of distribution were identified for RIF and PZA, whereas body weight only influenced clearance for INH. In addition, males had higher RIF clearance and thus lower RIF exposure than women. Acetylator status was significantly associated with INH clearance as INH exposure in intermediate and fast acetylators was significantly lower than in slow acetylators, especially in low‐weight bands. Simulations also showed significantly lower drug exposures in low‐weight bands for all three drugs. Patients weighing <38 kg were respectively exposed to 30.4%, 45.9% and 18.0% lower area under the concentration‐time curve of RIF, INH and PZA than those weighing ≥70 kg. Higher doses by addition of one fixed‐dose combination tablet or 150 mg INH were simulated and found to be effective in improving INH drug exposures, especially in low‐weight bands. Conclusion PK variability of first‐line anti‐TB drugs is common in Chinese TB patients. The developed population PK models can be used to optimize drug exposures in Chinese patients. Moreover, standard dosing needs to be adjusted to increase target attainment.

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Therapeutic drug monitoring of isoniazid and rifampicin during anti-tuberculosis treatment in Auckland, New Zealand

Abstract: There were no clinically useful characteristics to guide use of TDM. Many patients had concentrations below international therapeutic intervals, but were successfully treated.

Cited by 9 publications

References 0 publications

Early interventions for diabetes related tuberculosis associate with hastened sputum microbiological clearance in Virginia, USA

Early interventions for diabetes related tuberculosis associate with hastened sputum microbiological clearance in Virginia, USA

Factors Influencing Tuberculosis Treatment Outcome in Adult Patients Treated with Thrice-Weekly Regimens in India

Drug exposure of first‐line anti‐tuberculosis drugs in China: A prospective pharmacological cohort study

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