Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance

Global PETTS Investigators

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background. Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined. Methods. Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens. Results. Of 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P <. 001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ≤1 to ≥5 (P <. 001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P <. 001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval,. 56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome. Conclusions. Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance.

Original languageEnglish
Pages (from-to)418-430
Number of pages13
JournalClinical Infectious Diseases
Volume62
Issue number4
DOIs
Publication statusPublished - 2015 Nov 4

Fingerprint

Multidrug-Resistant Tuberculosis
Drug Resistance
Pharmaceutical Preparations
Fluoroquinolones
Therapeutics
Extensively Drug-Resistant Tuberculosis
Lost to Follow-Up
Sputum
Cohort Studies
Prospective Studies
Confidence Intervals
Injections

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

Cite this

@article{b04d7b15965b4b25b4b37fe0c0204165,
title = "Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance",
abstract = "Background. Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined. Methods. Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens. Results. Of 1244 patients with MDR tuberculosis, 973 (78.2{\%}) had known outcomes and 232 (18.6{\%}) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8{\%} with plain MDR tuberculosis, 69.7{\%} with initial resistance to either a fluoroquinolone or an SLI, 37.5{\%} with acquired resistance to a fluoroquinolone or SLI, 29.3{\%} with initial and 13.0{\%} with acquired extensively drug-resistant tuberculosis (P <. 001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6{\%} to 92.3{\%} as the number of drugs proven effective increased from ≤1 to ≥5 (P <. 001 for trend), while acquired drug resistance decreased from 12{\%} to 16{\%} range, depending on the drug, down to 0{\%}-2{\%} (P <. 001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95{\%} confidence interval,. 56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome. Conclusions. Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance.",
author = "{Global PETTS Investigators} and Cegielski, {J. Peter} and Ekaterina Kurbatova and {Van Der Walt}, Martie and Jeannette Brand and Julia Ershova and Thelma Tupasi and Caoili, {Janice Campos} and Tracy Dalton and Carmen Contreras and Martin Yagui and Jaime Bayona and Charlotte Kvasnovsky and Vaira Leimane and Liga Kuksa and Chen, {Michael P.} and Via, {Laura E.} and Hwang, {Soo Hee} and Melanie Wolfgang and Volchenkov, {Grigory V.} and Tatiana Somova and Smith, {Sarah E.} and Somsak Akksilp and Wanpen Wattanaamornkiet and Kim, {Hee Jin} and Kim, {Chang Ki} and Kazennyy, {Boris Y.} and Tatiana Khorosheva and Kai Kliiman and Piret Viiklepp and Ruwen Jou and Huang, {Angela Song En} and Vasilyeva, {Irina A.} and Demikhova, {Olga V.} and Joey Lancaster and Ronel Odendaal and Lois Diem and Kathrine Tan and Walker, {Allison Taylor} and Erika Sigman and Beverly Metchock and Perez, {M. Therese C.} and Gler, {M. Tarcela} and Cesar Bonilla and Oswaldo Jave and Luis Asencios and Gloria Yale and Carmen Suarez and Inga Norvaisha and Girts Skenders and Ingrida Sture",
year = "2015",
month = "11",
day = "4",
doi = "10.1093/cid/civ910",
language = "English",
volume = "62",
pages = "418--430",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "4",

}

Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance. / Global PETTS Investigators.

In: Clinical Infectious Diseases, Vol. 62, No. 4, 04.11.2015, p. 418-430.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance

AU - Global PETTS Investigators

AU - Cegielski, J. Peter

AU - Kurbatova, Ekaterina

AU - Van Der Walt, Martie

AU - Brand, Jeannette

AU - Ershova, Julia

AU - Tupasi, Thelma

AU - Caoili, Janice Campos

AU - Dalton, Tracy

AU - Contreras, Carmen

AU - Yagui, Martin

AU - Bayona, Jaime

AU - Kvasnovsky, Charlotte

AU - Leimane, Vaira

AU - Kuksa, Liga

AU - Chen, Michael P.

AU - Via, Laura E.

AU - Hwang, Soo Hee

AU - Wolfgang, Melanie

AU - Volchenkov, Grigory V.

AU - Somova, Tatiana

AU - Smith, Sarah E.

AU - Akksilp, Somsak

AU - Wattanaamornkiet, Wanpen

AU - Kim, Hee Jin

AU - Kim, Chang Ki

AU - Kazennyy, Boris Y.

AU - Khorosheva, Tatiana

AU - Kliiman, Kai

AU - Viiklepp, Piret

AU - Jou, Ruwen

AU - Huang, Angela Song En

AU - Vasilyeva, Irina A.

AU - Demikhova, Olga V.

AU - Lancaster, Joey

AU - Odendaal, Ronel

AU - Diem, Lois

AU - Tan, Kathrine

AU - Walker, Allison Taylor

AU - Sigman, Erika

AU - Metchock, Beverly

AU - Perez, M. Therese C.

AU - Gler, M. Tarcela

AU - Bonilla, Cesar

AU - Jave, Oswaldo

AU - Asencios, Luis

AU - Yale, Gloria

AU - Suarez, Carmen

AU - Norvaisha, Inga

AU - Skenders, Girts

AU - Sture, Ingrida

PY - 2015/11/4

Y1 - 2015/11/4

N2 - Background. Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined. Methods. Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens. Results. Of 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P <. 001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ≤1 to ≥5 (P <. 001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P <. 001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval,. 56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome. Conclusions. Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance.

AB - Background. Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined. Methods. Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens. Results. Of 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P <. 001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ≤1 to ≥5 (P <. 001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P <. 001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval,. 56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome. Conclusions. Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance.

UR - http://www.scopus.com/inward/record.url?scp=84952985566&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84952985566&partnerID=8YFLogxK

U2 - 10.1093/cid/civ910

DO - 10.1093/cid/civ910

M3 - Article

C2 - 26508515

AN - SCOPUS:84952985566

VL - 62

SP - 418

EP - 430

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 4

ER -