Abstract
BackgroundMolecular resistance detection (MRD) of resistance to second-line anti-tuberculous drugs provides faster results than phenotypic tests, may shorten treatment and allow earlier separation among patients with and without second-line drug resistance.MethodsIn a decision-analytical model we simulated a cohort of patients diagnosed with TB in a setting where drug resistant TB is highly prevalent and requires initial hospitalization, to explore the potential benefits of a high-throughput MRD-assay for reducing potential nosocomial transmission of highly resistant strains, and total costs for diagnosis of drug resistance, treatment and hospitalization. In the base case scenario first-line drug resistance was diagnosed with WHO-endorsed molecular tests, and second-line drug resistance with culture and phenotypic methods. Three alternative scenarios were explored, each deploying high-throughput MRD allowing either detection of second-line mutations in cultured isolates, directly on sputum, or MRD with optimized markers.ResultsCompared to a base case scenario, deployment of high-throughput MRD reduced total costs by 17-21 %. The period during which nosocomial transmission may take place increased by 15 % compared to the base case if MRD had currently reported suboptimal sensitivity and required cultured isolates; increased by 7 % if direct sputum analysis were possible including in patients with smear-negative TB, and reduced by 24 % if the assay had improved markers, but was still performed on cultured isolates. Improved clinical sensitivity of the assay (additional markers) by more than 35 % would be needed to avoid compromising infection control.ConclusionsFurther development of rapid second-line resistance testing should prioritize investment in optimizing markers above investments in a platform for direct analysis of sputum.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-1205-4) contains supplementary material, which is available to authorized users.
Highlights
Molecular resistance detection (MRD) of resistance to second-line anti-tuberculous drugs provides faster results than phenotypic tests, may shorten treatment and allow earlier separation among patients with and without second-line drug resistance
We explored the potential of this high-throughput MRD technology for reducing nosocomial transmission ofXDR-TB after TB diagnosis and cost for treatment, hospitalization and diagnosis of drug resistance, assuming clinical accuracy as published for another MRD technology
Primary analysis Infectious period of time Following the distribution of drug-resistance patterns, our simulated cohort of 1000 patients diagnosed with TB had 59 patients withXDR, detectable by phenotypic drug susceptibility (DST)
Summary
Molecular resistance detection (MRD) of resistance to second-line anti-tuberculous drugs provides faster results than phenotypic tests, may shorten treatment and allow earlier separation among patients with and without second-line drug resistance. Patients with additional resistance to second-line drugs constitute 32 % of MDRpatients globally [1]. These include patients with extensively drug resistant (XDR) TB, i.e. resistance to any fluoroquinolone (FQ) and to at least one of three second-line injectable drugs (SLID) capreomycin, kanamycin and amikacin [2] in addition to multidrug-resistance, or with resistance to one of these drug-classes (preXDR-TB). In settings where additional resistance to second-line drugs is common, the influence of phenotypic DST on the selection of the proper initial treatment and containment of the spread of MDR-TB and (pre)XDR-TB is limited
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