Het doel van onze studie was om risicofactoren te bepalen die de blootstelling aan het medicijn kunnen beïnvloeden en hun verband met verlengde, langer dan 6 maanden durende, tbc-behandeling. Deze informatie is nuttig om het gebruik van medicijnen in een Nederlandse poliklinische setting te monitoren.
Samenvatting
Background: Antituberculosis drug concentrations in patients with tuberculosis (TB) can be affected during the treatment by different factors like diabetes mellitus (DM) and human immunodeficiency virus (HIV). Too low drug concentration may result in prolonged time to sputum conversion and too high drug concentration in adverse events. Early detection of too low or high drug concentrations by therapeutic drug monitoring (TDM) may help to optimize treatment. The aim of our study was to determine risk factors that may influence drug exposure and their association with extended, longer than 6 month, TB treatment. These data are useful to assess potential use of TDM in a Dutch outpatient setting.
Methods: A cross-sectional study was conducted. Surveillance data in 2010-2013 of the region Haaglanden, The Netherlands, was obtained from the National TB Register (NTROSIRIS) database. Patients with smear and culture positive pulmonary TB were included.
Patients were divided into 2 groups according to the duration of TB treatment by the cutoff value of 200 days. Demographic, clinical, radiological and microbiological data from electronic health record (EPD), the Tuberculosis Information System “Tubis” and in-patient medical records were evaluated. The descriptive, univariable and multivariable logistic regression analysis were performed to assess the association between the risk factors that may influence drug concentrations and the extended TB treatment.
Results: Out of the 285 culture positive TB patients reported in 2010-2013 in region Haaglanden, 102 (36%) had smear- and culture positive pulmonary TB and 90 of them were eligible for analysis: the data of 46 patients treated ≥ 200 days and 44 patients treated ≤ 199 days were investigated. The age, sex and race distribution was similar in both patients groups. Extended TB treatment was associated with higher frequency of symptoms, presumed to be due to adverse drug reactions (OR 2.39 95% CI: 1.01-5.69), drug-induced
hepatotoxicity (DIH) (OR: 13.51; 95% CI: 1.66-109.82) and longer than 2 month smear and culture conversion rate (OR: 11.00; 95% CI: 1.24-97.96 and OR: 8.56; 95% CI: 1.53-47.96). The multivariable logistic analysis showed development of DIH during the TB treatment as single statistically strong factor, contributed to extension of TB treatment.
Conclusion: DIH was determined to be significant independent predictors of extended TB treatment. This result will need the further prospective study to determine mutual role of pharmacokinetic and pharmacogenetic diagnostic among the TB patients with ATD induced liver injury to optimize the TB treatment. Also larger prospective study is necessary for further exploration of the significance of delay sputum conversion in relation to TB drug exposure. The identification of TB patients with risk factors, related to drug concentration and at the same time contributing to extended treatment, helps in the better management of TB treatment