Suboptimal moxifloxacin and levofloxacin drug exposure during treatment of patients with multidrug-resistant tuberculosis: results from a prospective study in China

2020 ◽  
pp. 2003463
Author(s):  
Lina Davies Forsman ◽  
Katarina Niward ◽  
Johanna Kuhlin ◽  
Xubin Zheng ◽  
Rongrong Zheng ◽  
...  
Keyword(s):  
Prospective Study ◽  
Drug Exposure ◽  
Multidrug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
A Prospective Study

scholarly journals Treatment outcome among cases of multidrug-resistant tuberculosis (MDR TB) in Western India: A prospective study

2016 ◽  
Vol 9 (4) ◽  
pp. 478-484 ◽  
Author(s):  
Sangita V. Patel ◽  
Kapil B. Nimavat ◽  
Patel B. Alpesh ◽  
Lipy K. Shukla ◽  
Kalpita S. Shringarpure ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Prospective Study ◽  
Multidrug Resistant ◽  
Western India ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
A Prospective Study

scholarly journals Effect of tablet crushing on drug exposure in the treatment of multidrug-resistant tuberculosis

2019 ◽  
Vol 23 (10) ◽  
pp. 1068-1074 ◽  
Author(s):  
R. Court ◽  
M. T. Chirehwa ◽  
L. Wiesner ◽  
N. de Vries ◽  
J. Harding ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Geometric Mean ◽  
Area Under The Curve ◽  
Compartmental Analysis ◽  
Multidrug Resistant ◽  
Geometric Mean Ratio ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

SETTING: Treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) are poor. Due to drug toxicity and a long treatment duration, approximately half of patients are treated successfully. Medication is often crushed for patients who have difficulty swallowing whole tablets. Whether crushing tablets affects drug exposure in MDR-TB treatment is not known.OBJECTIVE AND DESIGN: We performed a sequential pharmacokinetic study in patients aged >18 years on MDR-TB treatment at two hospitals in Cape Town, South Africa. We compared the bioavailability of pyrazinamide, moxifloxacin, isoniazid (INH), ethambutol and terizidone when the tablets were crushed and mixed with water before administration vs. swallowed whole. We sampled blood at six time points over 10 h under each condition separated by 2 weeks. Non-compartmental analysis was used to derive the key pharmacokinetic measurements.RESULTS: Twenty participants completed the study: 15 were men, and the median age was 31.5 years. There was a 42% reduction in the area under the curve AUC0–10 of INH when the tablets were crushed compared with whole tablets (geometric mean ratio 58%; 90%CI 47–73). Crushing tablets of pyrazinamide, moxifloxacin, ethambutol and terizidone did not affect the bioavailability significantly.CONCLUSION: We recommend that crushing of INH tablets in the MDR-TB treatment regimen be avoided. Paediatric INH formulations may be a viable alternative if the crushing of INH tablets is indicated.

scholarly journals Dried Blood Spot Analysis for Therapeutic Drug Monitoring of Linezolid in Patients with Multidrug-Resistant Tuberculosis

2012 ◽  
Vol 56 (11) ◽  
pp. 5758-5763 ◽  
Author(s):  
D. H. Vu ◽  
M. S. Bolhuis ◽  
R. A. Koster ◽  
B. Greijdanus ◽  
W. C. M. de Lange ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Multidrug Resistant ◽  
Dried Blood Spot ◽  
Therapeutic Drug ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Blood Spot

ABSTRACTLinezolid is a promising antimicrobial agent for the treatment of multidrug-resistant tuberculosis (MDR-TB), but its use is limited by toxicity. Therapeutic drug monitoring (TDM) may help to minimize toxicity while adequate drug exposure is maintained. Conventional plasma sampling and monitoring might be hindered in many parts of the world by logistical problems that may be solved by dried blood spot (DBS) sampling. The aim of this study was to develop and validate a novel method for TDM of linezolid in MDR-TB patients using DBS sampling. Plasma, venous DBS, and capillary DBS specimens were obtained simultaneously from eight patients receiving linezolid. A DBS sampling method was developed and clinically validated by comparing DBS with plasma results using Passing-Bablok regression and Bland-Altman analysis. This study showed that DBS analysis was reproducible and robust. Accuracy and between- and within-day precision values from three validations presented as bias and coefficient of variation (CV) were less than 17.2% for the lower limit of quantification and less than 7.8% for other levels. The method showed a high recovery of approximately 95% and a low matrix effect of less than 8.7%. DBS specimens were stable at 37°C for 2 months and at 50°C for 1 week. The ratio of the concentration of linezolid in DBS samples to that in plasma was 1.2 (95% confidence interval [CI], 1.12 to 1.27). Linezolid exposure calculated from concentrations DBS samples and plasma showed good agreement. In conclusion, DBS analysis of linezolid is a promising tool to optimize linezolid treatment in MDR-TB patients. An easy sampling procedure and high sample stability may facilitate TDM, even in underdeveloped countries with limited resources and where conventional plasma sampling is not feasible.

scholarly journals An inexpensive, efficient and safe regimen containing Pasiniazid for MDR-TB in high Tuberculosis epidemic areas – A prospective study in China

2020 ◽  
Author(s):  
Wenwen Sun ◽  
Qin Tang ◽  
Jie Wang ◽  
Jinhui Yang ◽  
Fangyou Yu ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Success Rate ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
P Value ◽  
Prospective Clinical Study ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
A Prospective Study

Abstract Background: MDR-TB（multidrug-resistant tuberculosis） remains the challenge with low success rate of treatment. Pasiniazid had been applied in China for two decades, but relevant clinical studies are rare. To verify the efficacy and safety of a regimen containing pasiniazid on MDR-TB, a prospective clinical study was conducted in China. Methods: Patients with MDR-TB satisfied with inclusion criteria were prospectively enrolled into the study from 2017 June to 2018 Dec, given the regimen and followed up, observed the treatment outcome and adverse effect of drugs made up the regimen.Results: A total of 114 patients diagnosed as MDR Pulmonary tuberculosis(MDR-PTB) were enrolled into the study and given the regimen with six months of Capremycin(Cm), Levofloxacin(Lfx), Cycloserine(Cs), Protionamide(Pto), Pyrazinamide(Z) and Pasiniazid（Pa）, followed by 12 months of LfxCsPtoZPa. The overall treatment success rate in all enrolled patients was 79.8% (91/114) while it was significantly higher in newly treated MDR-PTB (91.7%, 33/36) than that in retreated MDR-PTB(74.4%，58/78, p value was 0.03); Patients infected with strains resistant to fluoroquinolones impacted the treatment outcome (P<0.05) while other drugs did not (P >0.05). Pasiniazid was taken safely without adverse reaction during the course of treatment.Conclusions: The long term of anti-MDR-PTB regimen containing Pasiniazid was proved to be effective, safe and inexpensive although it contained injectable agents. This regimen is suited to be applied in areas with poor resource and high TB burden.

scholarly journals Pharmacokinetics of bedaquiline, delamanid and clofazimine in patients with multidrug-resistant tuberculosis

2020 ◽  
Author(s):  
Wael A Alghamdi ◽  
Mohammad H Al-Shaer ◽  
Maia Kipiani ◽  
Ketevan Barbakadze ◽  
Lali Mikiashvili ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Strong Association ◽  
Compartmental Analysis ◽  
Multidrug Resistant ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Drug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Liquid Chromatography Tandem Mass

Abstract Background Pharmacokinetic data are needed for newly implemented anti-tuberculosis drugs to help optimize their use. Objectives To help fill existing knowledge gaps, we evaluated the pharmacokinetic parameters of novel and repurposed anti-tuberculosis drugs among patients with drug-resistant pulmonary tuberculosis. Methods A prospective cohort study among patients ≥16 years with confirmed pulmonary drug-resistant TB was conducted in Tbilisi, Georgia. Patients receiving bedaquiline, delamanid and/or clofazimine were included. Blood samples were collected 4–6 weeks after drug initiation, and serum concentrations were measured using validated liquid chromatography tandem mass spectrometry assays. A non-compartmental analysis was performed, and the association of exposure parameters with covariates was explored. Results Among 99 patients, the average age and weight were 40 years and 65 kg, respectively. The median Cmin was 0.68 mg/L for bedaquiline, 0.17 mg/L for delamanid, and 0.52 mg/L for clofazimine. The median AUC0–24 was 30.6 mg·h/L for bedaquiline, 16.1 mg·h/L for clofazimine, and the AUC0–12 was 2.9 mg·h/L for delamanid. Among the significant covariates associated with drug exposure parameters were weight and sex for bedaquiline, alcohol use for delamanid, and weight for clofazimine. Conclusions We found a strong association of weight with bedaquiline and clofazimine exposure parameters, suggesting the need for weight-based dosing for those agents.

scholarly journals High frequency of resistance to the drugs isoniazid and rifampicin among tuberculosis cases in the city of Cabo de Santo Agostinho, an urban area in Northeastern Brazil

2008 ◽  
Vol 41 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Marcilio Baliza ◽  
Artur Henrique Bach ◽  
Gabriel Lobo de Queiroz ◽  
Inês Cardoso Melo ◽  
Maria Madileuza Carneiro ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acquired Resistance ◽  
Multidrug Resistant ◽  
Northeastern Brazil ◽  
Tuberculosis Transmission ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Susceptibility Tests ◽  
A Prospective Study ◽  
The City

The objective of the present study was to investigate the frequency and risk factors for developing multidrug-resistant tuberculosis in Cabo de Santo Agostinho, PE. This was a prospective study conducted from 2000 to 2003, in which suspected cases were investigated using bacilloscopy and culturing. Out of 232 confirmed cases of tuberculosis, culturing and antibiotic susceptibility tests were performed on 174. Thirty-five of the 174 cultures showed resistance to all drugs. The frequencies of primary and acquired resistance to any drug were 14% and 50% respectively, while the frequencies of primary and acquired multidrug resistance were 8.3% and 40%. Previous tuberculosis treatment and abandonment of treatment were risk factors for drug resistance. The high levels of primary and acquired resistance to the combination of isoniazid and rifampicin contributed towards the difficulties in controlling tuberculosis transmission in the city.

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