Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis

Global Preserving Effective TB Treatment Study (PETTS) Investigatorsa

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Background. Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. Methods. To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC. Results. In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16-.47) for XDR tuberculosis, 0.28 (.17-.45) for FQ, and 0.15 (.06-.39) to 0.60 (.34-1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07-.62) for acquired XDR tuberculosis and 0.23 (.09-.59) for acquired FQ resistance. Conclusions. Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards.

Original languageEnglish
Pages (from-to)1049-1063
Number of pages15
JournalClinical Infectious Diseases
Volume59
Issue number8
DOIs
Publication statusPublished - 2014 Oct 15

Fingerprint

Multidrug-Resistant Tuberculosis
Drug Resistance
Methyl Green
Pharmaceutical Preparations
Fluoroquinolones
Therapeutics
Tuberculosis
Extensively Drug-Resistant Tuberculosis
Sputum
Pulmonary Tuberculosis
Odds Ratio
Confidence Intervals
Injections

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Global Preserving Effective TB Treatment Study (PETTS) Investigatorsa (2014). Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis. Clinical Infectious Diseases, 59(8), 1049-1063. https://doi.org/10.1093/cid/ciu572
Global Preserving Effective TB Treatment Study (PETTS) Investigatorsa. / Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis. In: Clinical Infectious Diseases. 2014 ; Vol. 59, No. 8. pp. 1049-1063.
@article{1f2b21f05f424fdbb93dfb823d533b07,
title = "Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis",
abstract = "Background. Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. Methods. To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC. Results. In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9{\%}) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2{\%}) acquired fluoroquinolone (FQ) resistance, and 56 (7.8{\%}) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95{\%} confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16-.47) for XDR tuberculosis, 0.28 (.17-.45) for FQ, and 0.15 (.06-.39) to 0.60 (.34-1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95{\%} CIs) were 0.21 (.07-.62) for acquired XDR tuberculosis and 0.23 (.09-.59) for acquired FQ resistance. Conclusions. Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards.",
author = "{Global Preserving Effective TB Treatment Study (PETTS) Investigatorsa} and Cegielski, {J. Peter} and Tracy Dalton and Martin Yagui and Wanpen Wattanaamornkiet and Volchenkov, {Grigory V.} and Via, {Laura E.} and {Van Der Walt}, Martie and Thelma Tupasi and Smith, {Sarah E.} and Ronel Odendaal and Vaira Leimane and Charlotte Kvasnovsky and Tatiana Kuznetsova and Ekaterina Kurbatova and Tiina Kummik and Liga Kuksa and Kai Kliiman and Kiryanova, {Elena V.} and Kim, {Hee Jin} and Kim, {Chang Ki} and Kazennyy, {Boris Y.} and Ruwen Jou and Huang, {Wei Lun} and Julia Ershova and Erokhin, {Vladislav V.} and Lois Diem and Carmen Contreras and Sangnae Cho and Chernousova, {Larisa N.} and Chen, {Michael P.} and Caoili, {Janice Campos} and Jaime Bayona and Somsak Akksilp",
year = "2014",
month = "10",
day = "15",
doi = "10.1093/cid/ciu572",
language = "English",
volume = "59",
pages = "1049--1063",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "8",

}

Global Preserving Effective TB Treatment Study (PETTS) Investigatorsa 2014, 'Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis', Clinical Infectious Diseases, vol. 59, no. 8, pp. 1049-1063. https://doi.org/10.1093/cid/ciu572

Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis. / Global Preserving Effective TB Treatment Study (PETTS) Investigatorsa.

In: Clinical Infectious Diseases, Vol. 59, No. 8, 15.10.2014, p. 1049-1063.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis

AU - Global Preserving Effective TB Treatment Study (PETTS) Investigatorsa

AU - Cegielski, J. Peter

AU - Dalton, Tracy

AU - Yagui, Martin

AU - Wattanaamornkiet, Wanpen

AU - Volchenkov, Grigory V.

AU - Via, Laura E.

AU - Van Der Walt, Martie

AU - Tupasi, Thelma

AU - Smith, Sarah E.

AU - Odendaal, Ronel

AU - Leimane, Vaira

AU - Kvasnovsky, Charlotte

AU - Kuznetsova, Tatiana

AU - Kurbatova, Ekaterina

AU - Kummik, Tiina

AU - Kuksa, Liga

AU - Kliiman, Kai

AU - Kiryanova, Elena V.

AU - Kim, Hee Jin

AU - Kim, Chang Ki

AU - Kazennyy, Boris Y.

AU - Jou, Ruwen

AU - Huang, Wei Lun

AU - Ershova, Julia

AU - Erokhin, Vladislav V.

AU - Diem, Lois

AU - Contreras, Carmen

AU - Cho, Sangnae

AU - Chernousova, Larisa N.

AU - Chen, Michael P.

AU - Caoili, Janice Campos

AU - Bayona, Jaime

AU - Akksilp, Somsak

PY - 2014/10/15

Y1 - 2014/10/15

N2 - Background. Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. Methods. To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC. Results. In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16-.47) for XDR tuberculosis, 0.28 (.17-.45) for FQ, and 0.15 (.06-.39) to 0.60 (.34-1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07-.62) for acquired XDR tuberculosis and 0.23 (.09-.59) for acquired FQ resistance. Conclusions. Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards.

AB - Background. Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. Methods. To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC. Results. In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16-.47) for XDR tuberculosis, 0.28 (.17-.45) for FQ, and 0.15 (.06-.39) to 0.60 (.34-1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07-.62) for acquired XDR tuberculosis and 0.23 (.09-.59) for acquired FQ resistance. Conclusions. Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards.

UR - http://www.scopus.com/inward/record.url?scp=84921053905&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84921053905&partnerID=8YFLogxK

U2 - 10.1093/cid/ciu572

DO - 10.1093/cid/ciu572

M3 - Article

C2 - 25057101

AN - SCOPUS:84921053905

VL - 59

SP - 1049

EP - 1063

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 8

ER -

Global Preserving Effective TB Treatment Study (PETTS) Investigatorsa. Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis. Clinical Infectious Diseases. 2014 Oct 15;59(8):1049-1063. https://doi.org/10.1093/cid/ciu572