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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Plasma drug activity in patients on treatment for multidrug-resistant tuberculosis
Antimicrobial Agents and Chemotherapy, Volume 58, No. 2, Year 2014
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Description
Little is known about plasma drug concentrations relative to quantitative susceptibility in patients with multidrug-resistant tuberculosis (MDR-TB). We previously described a TB drug activity (TDA) assay that determines the ratio of the time to detection of plasma-cocultured Mycobacterium tuberculosis versus control growth in a Bactec MGIT system. Here, we assess the activity of individual drugs in a typical MDR-TB regimen using the TDA assay. We also examined the relationship of the TDA to the drug concentration at 2 h (C2) and the MICs among adults on a MDR-TB regimen in Tanzania. These parameters were also compared to the treatment outcome of sputum culture conversion. Individually, moxifloxacin yielded superior TDA results versus ofloxacin, and only moxifloxacin and amikacin yielded TDAs equivalent to a-2-log killing. In the 25 patients enrolled on a regimen of kanamycin, levofloxacin, ethionamide, pyrazinamide, and cycloserine, the C2 values were found to be below the expected range for levofloxacin in 13 (52%) and kanamycin in 10 (40%). Three subjects with the lowest TDA result (<1.5, a finding indicative of poor killing) had significantly lower kanamycin C2/MIC ratios than subjects with a TDA of>1.5 (9.8±8.7 versus 27.0±19.1; P=0.04). The mean TDAs were 2.52±0.76 in subjects converting to negative in<2 months and 1.88±0.57 in subjects converting to negative in>2 months (P=0.08). In Tanzania, MDR-TB drug concentrations were frequently low, and a wide concentration/ MIC range was observed that affected plasma drug activity ex vivo. An opportunity exists for pharmacokinetic optimization in current MDR-TB regimens, which may improve treatment response. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Mpagama, Stellah George
Tanzania, Kilimanjaro
Kibong'oto National Tuberculosis Hospital
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Ndusilo, Norah D.
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Stroup, Suzanne E.
United States, Charlottesville
University of Virginia
Kumburu, Happiness Houka
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Peloquin, Charles Arthur
United States, Gainesville
University of Florida
Gratz, Jean C.
United States, Charlottesville
University of Virginia
Houpt, Eric R.
United States, Charlottesville
University of Virginia
Kibiki, Gibson S.
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Heysell, Scott Kirkland
United States, Charlottesville
University of Virginia
Statistics
Citations: 35
Authors: 9
Affiliations: 4
Identifiers
Doi:
10.1128/AAC.01549-13
ISSN:
00664804
e-ISSN:
10986596
Research Areas
Infectious Diseases
Study Approach
Quantitative
Study Locations
Tanzania