Modeling of second-line drug behavior in the treatment of tuberculosis using Petri net

ABSTRACT Early detection of resistance to second-line antituberculosis drugs is important for the management of multidrug-resistant tuberculosis (MDR-TB). The GenoType MTBDR sl version 2.0 (VER 2.0) line probe assay has been redesigned for molecular detection of resistance-conferring mutations of fluoroquinolones (FLQ) ( gyrA and gyrB genes) and second-line injectable drugs (SLID) ( rrs and eis genes). The study evaluated the diagnostic performance of the GenoType MTBDR sl VER 2.0 assay for the detection of second-line drug resistance compared with phenotypic drug susceptibility testing (DST), using the Bactec MGIT 960 system on Mycobacterium tuberculosis complex isolates from South Africa. A total of 268 repository isolates collected between 2012 and 2014, which were rifampin monoresistant or MDR based on DST, were selected. MTBDR sl VER 2.0 testing was performed on these isolates and the results analyzed. The MTBDR sl VER 2.0 sensitivity and specificity indices for culture isolates were the following: FLQ, 100% (95% confidence interval [CI] 95.8 to 100%) and 98.9% (95% CI, 96.1 to 99.9%); SLID, 89.2% (95% CI, 79.1 to 95.6%) and 98.5% (95% CI, 95.7 to 99.7%). The sensitivity and specificity observed for individual SLID were the following: amikacin, 93.8% (95% CI, 79.2 to 99.2%) and 98.5% (95% CI, 95.5 to 99.7%); kanamycin, 89.2% (95% CI, 79.1 to 95.6%) and 98.5% (95% CI, 95.5 to 99.7%); and capreomycin, 86.2% (95% CI, 68.3 to 96.1%) and 95.9% (95% CI, 92.2 to 98.2%). An interoperator reproducibility of 100% and an overall interlaboratory performance of 93% to 96% were found. The overall improvement in sensitivity and specificity with excellent reproducibility makes the GenoType MTBDR sl VER 2.0 a highly suitable tool for rapid screening of clinical isolates for second-line drug resistance for use in high-burden TB/HIV settings.

Download Full-text

SODIUM CROMOGLYCATE USED MAINLY AS SECOND-LINE DRUG IN THE USA

InPharma ◽

10.1007/bf03300040 ◽

1982 ◽

Vol 326 (1) ◽

pp. 2-3

Keyword(s):

Sodium Cromoglycate ◽

Second Line ◽

The Usa ◽

Line Drug

Download Full-text

Evaluation of the microscopic observation drug susceptibility assay for the detection of first- and second-line drug susceptibility forMycobacterium tuberculosis

European Respiratory Journal ◽

10.1183/13993003.02215-2016 ◽

2017 ◽

Vol 49 (4) ◽

pp. 1602215 ◽

Cited By ~ 1

Author(s):

Donald G. Catanzaro ◽

Andre P. Trollip ◽

Marva Seifert ◽

Sophia B. Georghiou ◽

Richard S. Garfein ◽

...

Keyword(s):

Microscopic Observation ◽

Drug Susceptibility ◽

Second Line ◽

Line Drug ◽

Susceptibility Assay

Download Full-text

Real-world systemic therapy treatment patterns for squamous cell carcinoma of the head and neck in Canada

Current Oncology ◽

10.3747/co.26.3946 ◽

2019 ◽

Vol 26 (2) ◽

Cited By ~ 1

Author(s):

K. Byrne ◽

P. Hallworth ◽

A. Abbas Tahami Monfared ◽

A. Moshyk ◽

J. W. Shaw

Keyword(s):

Squamous Cell Carcinoma ◽

Clinical Practice ◽

Drug Treatment ◽

Real World ◽

Treatment Patterns ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Line Drug ◽

First Line Treatment

Background In the present study, we examined real-world treatment patterns for squamous cell carcinoma of the head and neck (scchn) in Canada, which are largely unknown.Methods Oncologists across Canada provided data for disease history, characteristics, and treatment patterns during May–July 2016 for 6–8 consecutive patients receiving first-line or second-line drug treatment for scchn (including locally advanced and recurrent or metastatic disease).Results Information from 16 physicians for 109 patients receiving drug treatment for scchn was provided; 1 patient was excluded from the treatment-pattern analysis. Median age in the cohort was 63 years [interquartile range (iqr): 57–68 years], and 24% were current smokers, with a mean exposure of 26.2 ± 12.7 pack–years. The most common tumour site was the oropharynx (48%). Most patients (84%) received platinum-based regimens as first-line treatment (44% received cisplatin monotherapy). Use of cetuximab-based regimens as first-line treatment was limited (17%). Of 53 patients receiving second-line treatment, 87% received a first-line platinum-based regimen. Median time between first-line treatment with a platinum-based regimen and initiation of second-line treatment was 55 days (iqr: 20–146 days). The most common second-line regimen was cetuximab monotherapy (43%); platinum-based regimens were markedly infrequent (13%).Conclusions Our analysis provides real-world insight into scchn clinical practice patterns in Canada, which could inform reimbursement decision-making. High use of platinum-based regimens in first-line drug treatment was generally reflective of treatment guidelines; cetuximab use in the second-line was higher than anticipated. Additional real-world studies are needed to understand the effect of novel therapies such as immuno-oncology agents on clinical practice and outcomes, particularly for recurrent or metastatic scchn.

Download Full-text