Use of Nonlinear Mixed-Effects Analysis for Improved Precision of Early Pharmacodynamic Measures in Tuberculosis Treatment

ABSTRACT Nonlinear mixed-effects analysis of serial sputum colony-counting data supports the existence of two bacillary subpopulations in sputum, eliminated at different rates. It distinguishes between combination regimens, removes bias, and greatly improves precision, with significant implications for the analysis of surrogate endpoints of “sterilization” in the development of new antituberculosis regimens.

[1]  D. Mitchison,et al.  The early bactericidal activity of drugs in patients with pulmonary tuberculosis. , 2015, The American review of respiratory disease.

[2]  P. Venkatesan,et al.  Bactericidal Action of Gatifloxacin, Rifampin, and Isoniazid on Logarithmic- and Stationary-Phase Cultures of Mycobacterium tuberculosis , 2005, Antimicrobial Agents and Chemotherapy.

[3]  D. Mitchison,et al.  Predictive in vitro models of the sterilizing activity of anti-tuberculosis drugs. , 2004, Current pharmaceutical design.

[4]  T. Burdz,et al.  Evaluation of sputum decontamination methods for Mycobacterium tuberculosis using viable colony counts and flow cytometry. , 2003, Diagnostic microbiology and infectious disease.

[5]  C. Doré,et al.  Bactericidal and sterilizing activities of antituberculosis drugs during the first 14 days. , 2003, American journal of respiratory and critical care medicine.

[6]  John L. Johnson,et al.  Whole blood bactericidal activity during treatment of pulmonary tuberculosis. , 2003, The Journal of infectious diseases.

[7]  P. Bardin,et al.  Localisation of mycobacterial DNA and mRNA in human tuberculous granulomas. , 2002, Journal of microbiological methods.

[8]  S. Gillespie,et al.  A reiterative method for calculating the early bactericidal activity of antituberculosis drugs. , 2002, American journal of respiratory and critical care medicine.

[9]  D. Mitchison,et al.  Serial counts of Mycobacterium tuberculosis in sputum as surrogate markers of the sterilising activity of rifampicin and pyrazinamide in treating pulmonary tuberculosis , 2001, BMC pulmonary medicine.

[10]  V. Carey,et al.  Mixed-Effects Models in S and S-Plus , 2001 .

[11]  D. Mitchison,et al.  A multicentre study of the early bactericidal activity of anti-tuberculosis drugs. , 2000, The Journal of antimicrobial chemotherapy.

[12]  J. Ellner,et al.  Quantitative sputum bacillary load during rifampin-containing short course chemotherapy in human immunodeficiency virus-infected and non-infected adults with pulmonary tuberculosis. , 2000, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[13]  D. Mitchison,et al.  Studies on the treatment of tuberculosis undertaken by the British Medical Research Council Tuberculosis Units, 1946-1986, with relevant subsequent publications. , 1999, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[14]  M. Davidian,et al.  Nonlinear Models for Repeated Measurement Data , 1995 .

[15]  R. Brindle,et al.  Quantitative bacillary response to treatment in HIV-associated pulmonary tuberculosis. , 1993, The American review of respiratory disease.

[16]  S Senn,et al.  Analysis of serial measurements in medical research. , 1990, BMJ.

[17]  D. Mitchison.  The action of antituberculosis drugs in short-course chemotherapy. , 1985, Tubercle.

[18]  H. C. Sweany.  THE TUBERCLE BACILLUS IN THE PULMONARY LESION OF MAN: HISTOBACTERIOLOGY AND ITS BEARING ON THE THERAPY OF PULMONARY TUBERCULOSIS. , 1955 .

[19]  Tuberculosis. Scientific blueprint for tuberculosis drug development. , 2001, Tuberculosis.

[20]  D. Mitchison.  How drug resistance emerges as a result of poor compliance during short course chemotherapy for tuberculosis. , 1998, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.