Efficacy and Safety of Levofloxacin for the Treatment of Multi-Drug Resistant Tuberculosis (Opti-Q)

Project Description

Multi-Drug Resistant Tuberculosis (MDR-TB) is a growing threat to international health. A recent report from WHO estimated that over 440,000 new cases of MDR-TB occurred in 127 countries in 2008, causing 150,000 deaths; this represents a 55% increase in the number of cases since 2000. Current treatment regimens have only a 58-67% success rate, and as many as 20% of those who fail to respond to treatment die of tuberculosis; those who do not die become chronic carriers and spread MDR-TB to others.

Fluoroquinolones (FQ) are antibiotics that make up an important part of drug regimens for the treatment of MDR-TB.  Substantially better outcomes have consistently been seen in patients with MDR-TB who are treated with FQ, and newer FQ (levofloxacin, gatifloxacin and moxifloxacin) are the most potent anti-TB agents available for MDR-TB treatment. However, newer FQs such as gatifloxacin and moxifloxacin have been documented to have serious side effects. Although the efficacy of levofloxacin increases as exposure increases both in animal and human studies of TB, its efficacy at higher doses against TB in humans has not been studied. Thus, determination of the most efficacious and well-tolerated dose of levofloxacin is an important research priority. In this study, we will determine the levofloxacin dose and exposure that achieve the greatest reduction in TB bacteriae burden with acceptable tolerability by studying 100 adults with MDR-TB at sites in Peru and South Africa.

    This clinical trial will increase our ability to cure MDR-TB and help prevent the emergence of resistance to new TB drug classes by optimizing dosing and improving the effectiveness of an existing anti-TB agent, using a novel and versatile study design which more rapidly and efficiently identifies advances in this critical area. Construction of a clinical guideline to predict the optimal levofloxacin dose will allow more effective use of levofloxacin, particularly in areas with limited resources, where the burden of MDR-TB is the greatest.

    Project Details

    Principal Investigator C. Robert Horsburgh, Jr, MD, MUS
    Co-Investigators
    • Mamodikoe Makhene, MD, MPH
    • Andreas Diacon, MD
    • Nancy Dianis, MS
    • Kathleen Esenach, PhD
    • Eduardo Gotuzzo, MD
    • Leonid Lecca, MD
    • William Mac Kenzie, MD
    • Beverly Metchock, PhD
    • Carole Mitnick, DSc
    • Charles Peloquinn, Pharm. D
    • Patrick Phillips, PhD
    • Payam Nahid, MD
    • Tena Knudsen, BSN
    • Robin Mason, MBA, MS
    Collaborators
    • Centers for Disease Control and Prevention (CDC)
    • Westat, Inc.
    • Harvard Medical School
    • University of Arkansas Medical Sciences
    • University of Florida
    • Medical Research Council, UK
    • Socios en Salud (Partners in Health), Lima, Peru
    • University of Cayetana Heredia, Lima, Peru
    • TASK Applied Science, South Africa
    • Stellenbosch University, Cape Town, South Africa
    • Division of Microbiology and Infectious Diseases (DMID)
    Country(ies) Peru and South Africa
    Dates of Research 2013-2017
    Donor/Funder