Clinical Impact of Rapid Drug Susceptibility Testing to Accompany Fluoroquinolone-Containing Universal Tuberculosis Regimens: A Markov Model.
drug susceptibility testing
epidemiology of drug resistance
fluoroquinolones
modeling
tuberculosis treatment
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
31 12 2020
31 12 2020
Historique:
received:
10
09
2019
accepted:
06
12
2019
pubmed:
10
12
2019
medline:
29
4
2021
entrez:
10
12
2019
Statut:
ppublish
Résumé
To appropriately treat tuberculosis (TB) with regimens that combine novel and older drugs, evidence-based, context-specific strategies for drug-susceptibility testing (DST) will be required. We created a Markov state-transition model of 100 000 adults with TB receiving a novel, fluoroquinolone (FQ)-containing regimen. We estimated clinical outcomes and resource utilization with no FQ-DST, universal FQ-DST, or FQ-DST only for patients with rifampin-resistant TB ("targeted FQ-DST"). We considered scenarios of stronger (South Africa) and weaker (Southeast Asia) correlation of fluoroquinolone resistance with rifampin resistance, with sensitivity analysis for other setting and regimen characteristics. Relative to no FQ-DST, targeted FQ-DST increased cure of FQ-resistant TB by 7.5% (interquartile range [IQR], 6.7%-9.2%) in South Africa and 1.7% (IQR, 0.7%-2.5%) in Southeast Asia. However, rare FQ resistance among the more prevalent rifampin-susceptible TB accounted for 50% of FQ-resistant TB in South Africa and 83% in Southeast Asia. As a result, universal FQ-DST further increased cure of FQ-resistant TB by 3.4% (IQR, 2.3%-5.4%) in South Africa and 5.8% (IQR, 5.1%-6.3%) in Southeast Asia. With targeted FQ-DST, 1 additional patient was cured per 50 (IQR, 42-70) tests in South Africa and 44 (IQR, 37-51) in Southeast Asia. When expanding from targeted to universal FQ-DST, 1 additional cure required 3500 (IQR, 2300-5500) tests in South Africa and 410 (IQR, 370-450) in Southeast Asia. FQ-DST improved patient outcomes and was particularly important for high-risk patient groups and less robust regimens. A universal strategy was favored in generalized epidemics of fluoroquinolone resistance.
Sections du résumé
BACKGROUND
To appropriately treat tuberculosis (TB) with regimens that combine novel and older drugs, evidence-based, context-specific strategies for drug-susceptibility testing (DST) will be required.
METHODS
We created a Markov state-transition model of 100 000 adults with TB receiving a novel, fluoroquinolone (FQ)-containing regimen. We estimated clinical outcomes and resource utilization with no FQ-DST, universal FQ-DST, or FQ-DST only for patients with rifampin-resistant TB ("targeted FQ-DST"). We considered scenarios of stronger (South Africa) and weaker (Southeast Asia) correlation of fluoroquinolone resistance with rifampin resistance, with sensitivity analysis for other setting and regimen characteristics.
RESULTS
Relative to no FQ-DST, targeted FQ-DST increased cure of FQ-resistant TB by 7.5% (interquartile range [IQR], 6.7%-9.2%) in South Africa and 1.7% (IQR, 0.7%-2.5%) in Southeast Asia. However, rare FQ resistance among the more prevalent rifampin-susceptible TB accounted for 50% of FQ-resistant TB in South Africa and 83% in Southeast Asia. As a result, universal FQ-DST further increased cure of FQ-resistant TB by 3.4% (IQR, 2.3%-5.4%) in South Africa and 5.8% (IQR, 5.1%-6.3%) in Southeast Asia. With targeted FQ-DST, 1 additional patient was cured per 50 (IQR, 42-70) tests in South Africa and 44 (IQR, 37-51) in Southeast Asia. When expanding from targeted to universal FQ-DST, 1 additional cure required 3500 (IQR, 2300-5500) tests in South Africa and 410 (IQR, 370-450) in Southeast Asia.
CONCLUSIONS
FQ-DST improved patient outcomes and was particularly important for high-risk patient groups and less robust regimens. A universal strategy was favored in generalized epidemics of fluoroquinolone resistance.
Identifiants
pubmed: 31813958
pii: 5669959
doi: 10.1093/cid/ciz1179
pmc: PMC7778354
doi:
Substances chimiques
Antitubercular Agents
0
Fluoroquinolones
0
Pharmaceutical Preparations
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2889-2896Subventions
Organisme : NIAID NIH HHS
ID : K08 AI127908
Pays : United States
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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