Faculty Opinions recommendation of Pharmacokinetics and drug-drug interactions of lopinavir/ritonavir administered with first and second-line antituberculosis drugs in HIV-infected children treated for multidrug-resistant tuberculosis.

Introduction. Second-line antituberculosis drugs (SLDs) are used for treating multidrug-resistant tuberculosis (MDR-TB). Prolonged delays before confirming MDR-TB with drug susceptibility testing (DST) could result in transmission of drug-resistant strains and inappropriate use of SLDs, thereby increasing the risk of resistance to SLDs. This study investigated the diagnostic delay in DST and prevalence of baseline SLD resistance in Shanghai and described the distribution of SLD resistance with varied delays to DST.Methods. All registered patients from 2011 to 2013 in Shanghai were enrolled. Susceptibility to ofloxacin, amikacin, kanamycin, and capreomycin was tested. Total delay in DST completion was measured from the onset of symptoms to reporting DST results.Results. Resistance to SLDs was tested in 217 of the 276 MDR-TB strains, with 118 (54.4%) being resistant to at least one of the four SLDs. The median total delay in DST was 136 days. Patients with delay longer than median days were roughly twice more likely to have resistance to at least one SLD (OR 2.22, 95% CI 1.19–4.11).Conclusions. During prolonged delay in DST, primary and acquired resistance to SLDs might occur more frequently. Rapid diagnosis of MDR-TB, improved nosocomial infection controls, and regulated treatment are imperative to prevent SLD resistance.

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The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China

BMC Medicine ◽

10.1186/s12916-021-01932-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Chathika K Weerasuriya ◽

Rebecca C Harris ◽

C Finn McQuaid ◽

Fiammetta Bozzani ◽

Yunzhou Ruan ◽

...

Keyword(s):

Cost Effectiveness ◽

Cost Effective ◽

Multidrug Resistant ◽

Second Line ◽

Second Line Therapy ◽

China And India ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Line Therapy ◽

Mdr Tb

Abstract Background Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. Methods We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. Results By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69–72) and 72% (UI: 70–74), and the PSI vaccine by 31% (UI: 30–32) and 44% (UI: 42–47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8–1.1) and 1.1 million (UI: 0.9–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. Conclusions Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

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Resistance to second-line drugs in multidrug-resistant tuberculosis

The Lancet ◽

10.1016/s0140-6736(13)60341-4 ◽

2013 ◽

Vol 381 (9867) ◽

pp. 625 ◽

Cited By ~ 3

Author(s):

Bern-Thomas Nyang'wa ◽

Grania Brigden ◽

Philipp du Cros ◽

Leslie Shanks

Keyword(s):

Multidrug Resistant ◽

Second Line ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis

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Prevalence and Molecular Characterization of Second-Line Drugs Resistance among Multidrug-ResistantMycobacterium tuberculosisIsolates in Southwest of China

BioMed Research International ◽

10.1155/2017/4563826 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Y. Hu ◽

L. Xu ◽

Y. L. He ◽

Y. Pang ◽

N. Lu ◽

...

Keyword(s):

Gene Mutations ◽

Multidrug Resistant ◽

Rapid Screening ◽

Second Line ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Improper Use ◽

Mdr Tb

This study aimed to investigate the prevalence of multidrug-resistant tuberculosis (MDR-TB) isolates resistant to the second-line antituberculosis drugs (SLDs) and its association with resistant-related gene mutations inMycobacterium tuberculosis(M.tb) isolates from Southwest of China. There were 81 isolates resistant to at least one of the SLDs among 156 MDR-TB isolates (81/156, 51.9%). The rates of general resistance to each of the drugs were as follows: OFX (66/156, 42.3%), KAN (26/156, 16.7%), CAP (13/156, 8.3%), PTO (11/156, 7.1%), PAS (22/156, 14.1%), and AMK (20/156, 12.8%). Therefore, the most predominant pattern was resistant to OFX compared with other SLDs (P<0.001). The results of sequencing showed that 80.2% OFX-resistant MDR-TB isolates containedgyrAmutation and 88.5% KAN-resistant isolates hadrrsmutations with the most frequent mutation being A1401G. These results suggest that improper use of SLDs especially OFX is a real threat to effective MDR-TB treatment not only in China but also in the whole world. Furthermore the tuberculosis control agencies should carry out SLDs susceptibility testing and rapid screening in a broader population of TB patients immediately and the SLDs should be strictly regulated by the administration in order to maintain their efficacy to treat MDR-TB.

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Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug-Resistant Tuberculosis in India

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02410-17 ◽

2018 ◽

Vol 62 (5) ◽

Cited By ~ 7

Author(s):

Agibothu Kupparam Hemanth Kumar ◽

Alok Kumar ◽

Thiruvengadam Kannan ◽

Rakesh Bhatia ◽

Dipti Agarwal ◽

...

Keyword(s):

High Performance ◽

Linear Regression Analysis ◽

Multidrug Resistant ◽

Control Programme ◽

Second Line ◽

Time Curve ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

The Government

ABSTRACTWe studied the pharmacokinetics of levofloxacin (LFX), pyrazinamide (PZA), ethionamide (ETH), and cycloserine (CS) in children with multidrug-resistant tuberculosis (MDR-TB) who were being treated according to the Revised National TB Control Programme (RNTCP) guidelines in India. This observational, pharmacokinetic study was conducted in 25 children with MDR-TB at the Sarojini Naidu Medical College, Agra, India, who were being treated with a 24-month daily regimen. Serial blood samples were collected after directly observed administration of drugs. Estimations of plasma LFX, PZA, ETH, and CS were undertaken according to validated methods by high-performance liquid chromatography. Adverse events were noted at 6 months of treatment. The peak concentration (Cmax) of LFX was significantly higher in female than male children (11.5 μg/ml versus 7.3 μg/ml;P= 0.017). Children below 12 years of age had significantly higher ETH exposure (area under the concentration-time curve from 0 to 8 h [AUC0–8]) than those above 12 years of age (17.5 μg/ml · h versus 9.4 μg/ml;P= 0.030). Multiple linear regression analysis showed significant influence of gender onCmaxof ETH and age onCmaxand AUC0–8of CS. This is the first and only study from India reporting on the pharmacokinetics of LFX, ETH, PZA, and CS in children with MDR-TB treated in the Government of India program. More studies on the safety and pharmacokinetics of second-line anti-TB drugs in children with MDR-TB from different settings are required.

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