Serum Levels of Antituberculosis Drugs and Their Effect on Tuberculosis Treatment Outcome

Abstract

Therapeutic drug monitoring in tuberculosis remains controversial. We evaluated the relationship between antituberculosis drug levels in blood and clinical outcome. Serum concentrations of first-line antituberculosis drugs were measured in tuberculosis patients between March 2006 and April 2013. Venous blood was drawn 2 h after drug ingestion and was analyzed using highperformance liquid chromatography-tandem mass spectrometry. We retrospectively reviewed the data and determined the association of serum drug levels with clinical outcome. Among 413 patients, the prevalences of low serum concentrations of isoniazid (INH), rifampin (RMP), ethambutol (EMB), and pyrazinamide (PZA) were 59.9%, 27.8%, 12.8%, and 8.7%, respectively. The low INH group had a greater percentage of patients with a history of tuberculosis treatment (19.2% versus 11.0%; P ‫؍‬ 0.026) and was more likely to present with drug-resistant strains (17.6% versus 8.8%; P ‫؍‬ 0.049) than the normal INH group; however, low levels of INH, RMP, EMB, and PZA were not related to treatment outcome. Low INH level had a tendency to be associated with 2-month culture positivity, but it was not statistically significant (P ‫؍‬ 0.072) in multivariate analysis. Seventeen (4.1%) patients experienced a recurrence. However, the recurrence rate was not statistically different between the low and normal INH groups. Low serum INH may play a role in recurrence and in acquired drug resistance. However, the serum level of INH was not directly related to either treatment response or recurrence rate. The role and usefulness of therapeutic drug monitoring should be evaluated in further prospective studies.

Impact of the host environment on the antitubercular action of pyrazinamide

“…For example, Chideya et al [76] reported that patients with inadequate PZA levels in serum (adjusted for HIV status and CD4 + T cell counts) were at three times greater risk for poor outcome compared to patients with normal concentrations of PZA. However, data collected by Park et al [79] indicated that low serum concentrations of isoniazid rather than PZA had a slight association with TB recurrence and drug resistance.…”

Cohort profile of a study on outcomes related to tuberculosis and antiretroviral drug concentrations in Uganda: design, methods and patient characteristics of the SOUTH study

“… 5 Several authors have found that low anti-TB drug concentrations (pyrazinamide, rifampicin and isoniazid) were associated with poor TB treatment outcomes 7 13 19 20 while others did not. 8 21 22 Many of these studies were retrospective with small sample sizes and only a few included patients with HIV infection. This is an aspect that this study will explore further and contribute to the existing studies by providing prospectively collected data with a considerably large sample size including a population of severely immunosuppressed patients coinfected with TB/HIV who at a particularly high risk of poor TB treatment outcomes.…”

Serum isoniazid concentration in the patients as an indicator of the effectiveness and toxicity of tuberculosis treatment

“…6 On the other hand, the low level of isoniazid led to the drug resistance of M. tuberculosis and poor outcomes of TB-treatment. 7,8 Thus, scanty and controversy information is available on the association between isoniazid serum concentrations, treatment efficacy and toxicity. 9…”