TY - JOUR
T1 - Clinical impact of rapid drug susceptibility testing to accompany fluoroquinolone-containing universal tuberculosis regimens
T2 - A markov model
AU - Kendall, Emily A.
AU - Malhotra, Shelly
AU - Cook-Scalise, Sarah
AU - Dowdy, David W.
AU - Denkinger, Claudia M.
N1 - Funding Information:
This work was supported by the National Institutes of Health (grant number K08 AI127908 to E. A. K.).
Publisher Copyright:
© The Author(s) 2019.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
KW - Drug susceptibility testing
KW - Epidemiology of drug resistance
KW - Fluoroquinolones
KW - Modeling
KW - Tuberculosis treatment
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U2 - 10.1093/cid/ciz1179
DO - 10.1093/cid/ciz1179
M3 - Article
C2 - 31813958
AN - SCOPUS:85099326507
SN - 1058-4838
VL - 71
SP - 2889
EP - 2896
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 11
ER -