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1 June 2007

Volume 44, Number 11
Clinical Infectious Diseases 2007;44:1421–1427
© 2007 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2007/4411-0004$15.00
DOI: 10.1086/517536
MAJOR ARTICLE

Risk of Acquired Drug Resistance during Short‐Course Directly Observed Treatment of Tuberculosis in an Area with High Levels of Drug Resistance

Helen S. Cox,1,a

Stefan Niemann,2,a

Gabit Ismailov,3

Daribay Doshetov,4

Juan Daniel Orozco,3

Lucie Blok,5,b

Sabine Rüsch‐Gerdes,2 and

Yared Kebede5

1Australian International Health Institute, University of Melbourne, Australia; 2Forchungszentrum Borstel, National Reference Center for Mycobacteria, Borstel, Germany; 3Médecins Sans Frontières and 4Ministry of Health, Nukus, Karakalpakstan, Uzbekistan; and 5Médecins Sans Frontières, Amsterdam, The Netherlands

Background.Data on the performance of standardized short‐course directly observed treatment (DOTS) of tuberculosis (TB) in areas with high levels of drug resistance and on the potential impact of DOTS on amplification of resistance are limited. Therefore, we analyzed treatment results from a cross‐sectional sample of patients with TB enrolled in a DOTS program in an area with high levels of drug resistance in Uzbekistan and Turkmenistan in Central Asia.

Methods.Sputum samples for testing for susceptibility to 5 first‐line drugs and for molecular typing were obtained from patients starting treatment in 8 districts. Patients with sputum smear results positive for TB at the end of the intensive phase of treatment and/or at 2 months into the continuation phase were tested again.

Results.Among 382 patients with diagnoses of TB, 62 did not respond well to treatment and were found to be infected with an identical Mycobacterium tuberculosis strain when tested again; 19 of these patients had strains that developed new or additional drug resistance. Amplification occurred in only 1.2% of patients with initially susceptible or monoresistant TB strains, but it occurred in 17% of those with polyresistant strains (but not multidrug‐resistant strains, defined as strains with resistance to at least isoniazid and rifampicin) and in 7% of those with multidrug‐resistant strains at diagnosis. Overall, 3.5% of the patients not initially infected with multidrug‐resistant TB strains developed such strains during treatment. Amplification of resistance, however, was found only in polyresistant Beijing genotype strains.

Conclusions.High levels of amplification of drug resistance demonstrated under well‐established DOTS program conditions reinforce the need for implementation of DOTS‐Plus for multidrug‐resistant TB in areas with high levels of drug resistance. The strong association of Beijing genotype and amplification in situations of preexisting resistance is striking and may underlie the strong association between this genotype and drug resistance.

Received 19 December 2006; accepted 15 February 2007; electronically published 24 April 2007.

Reprints or correspondence: Dr. Stefan Niemann, Forschungszentrum Borstel, National Reference Center for Mycobacteria, Parkallee 18, D‐23845 Borstel, Germany ().

Cited by

Doosoo Jeon, Dohyung Kim, Hyungseok Kang, Jinhong Min, Nackmoon Sung, Soohee Hwang, Seungkew Park. (2009) Acquired Drug Resistance during Standardized Treatment with First-line Drugs in Patients with Multidrug-Resistant Tuberculosis. Tuberculosis and Respiratory Diseases 66:3, 198
Online publication date: 1-Feb-2009.
CrossRef
Christopher Dye. (2009) Doomsday postponed? Preventing and reversing epidemics of drug-resistant tuberculosis. Nature Reviews Microbiology 7:1, 81-87
Online publication date: 1-Feb-2009.
CrossRef
Beth Temple, Irene Ayakaka, Sam Ogwang, Helen Nabanjja, Susan Kayes, Susan Nakubulwa, William Worodria, Jonathan Levin, Moses Joloba, Alphonse Okwera, Kathleen D. Eisenach, Ruth McNerney, Alison M. Elliott, Peter G. Smith, Roy D. Mugerwa, Jerrold J. Ellner, and Edward C. Jones‐López. (2008) Rate and Amplification of Drug Resistance among Previously‐Treated Patients with Tuberculosis in Kampala, Uganda. Clinical Infectious Diseases 47:9, 1126-1134
Online publication date: 1-Nov-2008.
Abstract-Full Text-PDF Version (345 kB)
Jean-Pierre Zellweger. (2007) Treatment of tuberculosis. Expert Review of Respiratory Medicine 1:1, 85-97
Online publication date: 1-Sep-2007.
CrossRef

  • Presented in part: 35th World Conference on Lung Health of the International Union against Tuberculosis and Lung Disease, Paris, France, 28 October–1 November 2004 (poster abstract 253‐281).

  • H.S.C. and S.N. contributed equally to this study.

  • Present affiliation: Royal Tropical Institute, The Netherlands.

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