Drug susceptibility testing and mortality in patients treated for tuberculosis in high-burden countries: a multicentre cohort study.
Adolescent
Adult
Africa
Aged
Aged, 80 and over
Cohort Studies
Diagnostic Errors
Drug Resistance, Bacterial
Female
Humans
Male
Microbial Sensitivity Tests
/ methods
Middle Aged
Mycobacterium tuberculosis
/ drug effects
Peru
Sensitivity and Specificity
Survival Analysis
Thailand
Tuberculosis
/ drug therapy
Young Adult
Journal
The Lancet. Infectious diseases
ISSN: 1474-4457
Titre abrégé: Lancet Infect Dis
Pays: United States
ID NLM: 101130150
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
28
06
2018
revised:
07
10
2018
accepted:
29
10
2018
pubmed:
13
2
2019
medline:
26
5
2020
entrez:
13
2
2019
Statut:
ppublish
Résumé
Drug resistance is a challenge for the global control of tuberculosis. We examined mortality in patients with tuberculosis from high-burden countries, according to concordance or discordance of results from drug susceptibility testing done locally and in a reference laboratory. This multicentre cohort study was done in Côte d'Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand. We collected Mycobacterium tuberculosis isolates and clinical data from adult patients aged 16 years or older. Patients were stratified by HIV status and tuberculosis drug resistance. Molecular or phenotypic drug susceptibility testing was done locally and at the Swiss National Center for Mycobacteria, Zurich, Switzerland. We examined mortality during treatment according to drug susceptibility test results and treatment adequacy in multivariable logistic regression models adjusting for sex, age, sputum microscopy, and HIV status. We obtained M tuberculosis isolates from 871 patients diagnosed between 2013 and 2016. After exclusion of 237 patients, 634 patients with tuberculosis were included in this analysis; the median age was 33·2 years (IQR 26·9-42·5), 239 (38%) were women, 272 (43%) were HIV-positive, and 69 (11%) patients died. Based on the reference laboratory drug susceptibility test, 394 (62%) strains were pan-susceptible, 45 (7%) monoresistant, 163 (26%) multidrug-resistant (MDR), and 30 (5%) had pre-extensively or extensively drug resistant (pre-XDR or XDR) tuberculosis. Results of reference and local laboratories were concordant for 513 (81%) of 634 patients and discordant for 121 (19%) of 634. Overall, sensitivity to detect any resistance was 90·8% (95% CI 86·5-94·2) and specificity 84·3% (80·3-87·7). Mortality ranged from 6% (20 of 336) in patients with pan-susceptible tuberculosis treated according to WHO guidelines to 57% (eight of 14) in patients with resistant strains who were under-treated. In logistic regression models, compared with concordant drug susceptibility test results, the adjusted odds ratio of death was 7·33 (95% CI 2·70-19·95) for patients with discordant results potentially leading to under-treatment. Inaccurate drug susceptibility testing by comparison with a reference standard leads to under-treatment of drug-resistant tuberculosis and increased mortality. Rapid molecular drug susceptibility test of first-line and second-line drugs at diagnosis is required to improve outcomes in patients with MDR tuberculosis and pre-XDR or XDR tuberculosis. National Institutes of Allergy and Infectious Diseases, Swiss National Science Foundation, Swiss National Center for Mycobacteria.
Sections du résumé
BACKGROUND
Drug resistance is a challenge for the global control of tuberculosis. We examined mortality in patients with tuberculosis from high-burden countries, according to concordance or discordance of results from drug susceptibility testing done locally and in a reference laboratory.
METHODS
This multicentre cohort study was done in Côte d'Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand. We collected Mycobacterium tuberculosis isolates and clinical data from adult patients aged 16 years or older. Patients were stratified by HIV status and tuberculosis drug resistance. Molecular or phenotypic drug susceptibility testing was done locally and at the Swiss National Center for Mycobacteria, Zurich, Switzerland. We examined mortality during treatment according to drug susceptibility test results and treatment adequacy in multivariable logistic regression models adjusting for sex, age, sputum microscopy, and HIV status.
FINDINGS
We obtained M tuberculosis isolates from 871 patients diagnosed between 2013 and 2016. After exclusion of 237 patients, 634 patients with tuberculosis were included in this analysis; the median age was 33·2 years (IQR 26·9-42·5), 239 (38%) were women, 272 (43%) were HIV-positive, and 69 (11%) patients died. Based on the reference laboratory drug susceptibility test, 394 (62%) strains were pan-susceptible, 45 (7%) monoresistant, 163 (26%) multidrug-resistant (MDR), and 30 (5%) had pre-extensively or extensively drug resistant (pre-XDR or XDR) tuberculosis. Results of reference and local laboratories were concordant for 513 (81%) of 634 patients and discordant for 121 (19%) of 634. Overall, sensitivity to detect any resistance was 90·8% (95% CI 86·5-94·2) and specificity 84·3% (80·3-87·7). Mortality ranged from 6% (20 of 336) in patients with pan-susceptible tuberculosis treated according to WHO guidelines to 57% (eight of 14) in patients with resistant strains who were under-treated. In logistic regression models, compared with concordant drug susceptibility test results, the adjusted odds ratio of death was 7·33 (95% CI 2·70-19·95) for patients with discordant results potentially leading to under-treatment.
INTERPRETATION
Inaccurate drug susceptibility testing by comparison with a reference standard leads to under-treatment of drug-resistant tuberculosis and increased mortality. Rapid molecular drug susceptibility test of first-line and second-line drugs at diagnosis is required to improve outcomes in patients with MDR tuberculosis and pre-XDR or XDR tuberculosis.
FUNDING
National Institutes of Allergy and Infectious Diseases, Swiss National Science Foundation, Swiss National Center for Mycobacteria.
Identifiants
pubmed: 30744962
pii: S1473-3099(18)30673-X
doi: 10.1016/S1473-3099(18)30673-X
pmc: PMC6482382
mid: NIHMS1020127
pii:
doi:
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
298-307Subventions
Organisme : NIAID NIH HHS
ID : U01 AI096299
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI096186
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI069923
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI069911
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI069919
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI069907
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : U01 AI069924
Pays : United States
Investigateurs
Kathrin Zürcher
(K)
Matthias Egger
(M)
Lukas Fenner
(L)
Marie Ballif
(M)
Frédérique Chammartin
(F)
Sebastien Gagneux
(S)
Sonia Borrell
(S)
Miriam Reinhard
(M)
Erik C Boettger
(EC)
Peter Keller
(P)
Rico Hömke
(R)
Alash'le Abimiku
(A)
Nicholas Ezati
(N)
Marcel Yotebieng
(M)
Landry Wenzi
(L)
Martine Tabala
(M)
Helen Cox
(H)
Neesha Rockwood
(N)
Robin Warren
(R)
Elizabeth Streicher
(E)
Robert J Wilkinson
(RJ)
E Jane Carter
(EJ)
Lameck Diero
(L)
Jimena Collantes
(J)
Carlos Zamudio
(C)
Robin Huebner
(R)
Annette Sohn
(A)
Anchalee Avihingsanon
(A)
Tor Petersen
(T)
Kamon Kawkitinarong
(K)
Naruporn Kasipong
(N)
Joachim Gnokoro
(J)
Kouassi N'Guessan
(K)
Olivier Marcy
(O)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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