Optimizing treatment outcome of first-line anti-tuberculosis drugs: the role of therapeutic drug monitoring

Abstract

Although TDM of first-line anti-TB drugs has been successfully used in a limited number of specialized centers to improve treatment outcome in slow responders, a better characterization of the target PK and/or PK/PD parameters is in our opinion necessary to make it cost-effective.

Rifamycin action on RNA polymerase in antibiotic-tolerant Mycobacterium tuberculosis results in differentially detectable populations

“…Doses of RIF, INH, pyrazinamide (PZA), and ETH were selected based on mean peak drug concentrations (Cmax) achieved in patients' serum (36)(37)(38). For these studies, Mtb was starved in PBS for 4 wk, then exposed to the four drugs simultaneously for 5 d, with two different doses of RIF-one based on Cmax data (3 μg/mL), and one already shown to create DD Mtb (10 μM; 8.2 μg/mL).…”

Predictors of tuberculosis treatment success under the DOTS program in Namibia

“…Similar studies in South Africa and Uganda 25,26 have also associated poor treatment outcomes to the male gender, HIV co-infection, diagnostic and the sputum conversion at 2 months as well as the WHO TB regimen used 33 . In addition, coinfection with HIV and/or diabetes among TB patients, patient related demographic characteristics 34,35 , and pharmacokinetic variability among populations 36 . In addition in this study, poor treatment outcomes were as a result of defaulting of treatment and death.…”

“…However, in our study, patients who received treatment through a work placed based DOTS care increased their TSR by more than three times compared to other types of DOT providers. The results indicate the importance of optimizing the TB regimens 36,41,50 , strengthening the support DOTS support system and instigating a system to screen and monitor for risk for poor treatment outcomes among patients with HIV co-infection, and prior exposure to cotrimoxazole, to maximize the outcome of DOTS. The regional variation in TSR may be due population related characteristics and/or access and quality of health care at these facilities.…”

Simple and sensitive method for the analysis of 14 antituberculosis drugs using liquid chromatography/tandem mass spectrometry in human plasma

“…Up to the present day, therapeutic drug monitoring (TDM) for anti‐TB drugs has been shown to have potential benefits for the treatment of TB. Modifying the dosage based on monitoring results could shorten the individualized therapy time, improving efficacy and minimizing any side effects …”

“…Modifying the dosage based on monitoring results could shorten the individualized therapy time, improving efficacy and minimizing any side effects. 16,17 To apply TDM on large numbers of samples, multiplex quantification with liquid chromatography/tandem mass spectrometry (LC/MS/MS) is a powerful technique. Several LC/MS/MS methods for the simultaneous monitoring of anti-TB drugs have been reported.…”