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 language | English |
|---|---|
| Pages (from-to) | 418-430 |
| Number of pages | 13 |
| Journal | Clinical Infectious Diseases |
| Volume | 62 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2015 Nov 4 |
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All Science Journal Classification (ASJC) codes
- Microbiology (medical)
- Infectious Diseases
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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 journal › Article
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 -