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Antimicrobial Agents and Chemotherapy, September 2006, p. 3154-3156, Vol. 50, No. 9
0066-4804/06/$08.00+0     doi:10.1128/AAC.00774-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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

Geraint R. Davies,1* Richard Brindle,2 Saye H. Khoo,3 and Leon J. Aarons4

Wellcome Trust Centre for Clinical Tropical Medicine, University of Liverpool, Liverpool, United Kingdom,1 Department of Clinical Microbiology, Portsmouth Hospitals, Portsmouth, United Kingdom,2 Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom,3 School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, United Kingdom4

Received 20 June 2005/ Returned for modification 7 March 2006/ Accepted 12 June 2006

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.

* Corresponding author. Mailing address: Wellcome Trust-Mahidol University-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajavithi Road, Bangkok 10400, Thailand. Phone: 66 23549172. Fax: 66 23549169. E-mail: gerrydavies{at}doctors.org.uk.

Antimicrobial Agents and Chemotherapy, September 2006, p. 3154-3156, Vol. 50, No. 9
0066-4804/06/$08.00+0     doi:10.1128/AAC.00774-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • van den Boogaard, J., Kibiki, G. S., Kisanga, E. R., Boeree, M. J., Aarnoutse, R. E. (2009). New Drugs against Tuberculosis: Problems, Progress, and Evaluation of Agents in Clinical Development. Antimicrob. Agents Chemother. 53: 849-862 [Full Text]  


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