Drug Concentrations in the Treatment of MDR-TB Related to Minimum Inhibitory Concentrations

Summary

Multi-drug resistant tuberculosis (MDR-TB) is steadily increasing world-wide, urging for the need of improved treatment strategies. In order to protect the few available drugs that are left, ensuring adequate plasma concentrations of the drugs are important. Individualized therapy using plasma drug concentrations and minimal inhibitory concentration (MIC) determination may be of importance (1). The plasma drug concentrations and the MICs of the second-line drugs will be compared, aiming at increasing the knowledge about pharmacokinetic/pharmacodynamic (PK/PD) indices in the treatment of MDR-TB. In the future, the aim is an individualised therapy, where sub-therapeutic drug concentrations can be adjusted by the use of therapeutic drug monitoring (TDM). TDM in the treatment of MDR-TB may improve clinical outcome for the patients, but plasma concentrations must be assessed together with clinical and microbiological factors (2).

In this observational study the hypothesis is that the ratio between drug concentrations and MICs of the anti-tuberculous drugs, are correlated to the time to sputum culture conversion, the bacterial load measured as time to positive liquid culture (TTP) and clinical outcome. Consenting adult patients with pulmonary MDR-TB patients in China will be recruited. MIC-determination of Mycobacterium tuberculosis will be performed in BACTEC 960 MGIT and drug concentration will be determined at 2, 4 and 8 weeks after treatment initiation using liquid chromatography tandem mass spectrometry (LC-MS/MS), simultaneously assessing Dried Blood Spot (DBS) as a bio-sampling method. Sputum cultures will be obtained regularly throughout the treatment to measure the time to culture positivity (TTP). Clinical follow up according to WHO criteria will be performed at the end of treatment completion.

Conditions

• Tuberculosis, Multidrug Resistant

Sponsors & Collaborators

• Fudan University

  collaborator OTHER

• University Medical Center Groningen

  collaborator OTHER

• Karolinska Institutet

  lead OTHER

Principal Investigators

• Hu Yi, MD Ass Prof · Fudan University, Shanghai

• Sven Hoffner, Prof · Karolinska Institutet

• Biao Xu, Prof · Fudan University, Shanghai

• Thomas Schön, MD Ass Prof · Kalmar County Hospital

• Rongrong Zheng, MD · Xiamen CDC

• Lina Davies Forsman, MD · Karolinska Institutet, Department of Medicine, Unit of Infectious Diseases, Stockholm

• Xiangyang Yao, MD · Xiamen First Affiliated Hospital

• Jan-Willem Alffenaar, Prof PhamD · University Medical Center of Groningen

• Remco Koster, PhamD PhD · University Medical Center of Groningen

• Katarina Niward, MD · University Hospital, Linkoeping

• Judith Bruchfeld, MD Ass. Prof · Karolinska Institutet, Department of Medicine, Unit of Infectious Diseases, Stockholm

• Jakob Paues, MD, PhD · University Hospital, Linkoeping

• Johanna Kuhlin, MD, MSc · Karolinska Institutet

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-03-31

Primary Completion

2018-09-01

Completion

2020-06-01

Countries

• China

Study Locations