A Time-to-Event Pharmacodynamic Model Describing Treatment Response in Patients with Pulmonary Tuberculosis Using Days to Positivity in Automated Liquid Mycobacterial Culture

The pyrazinamide susceptibility breakpoint above which combination therapy fails

“…2,12,20 We wanted to take these into account, in order to further delineate the role of the CART analysis-derived susceptibility breakpoint. First, we examined the 2 month sputum conversion outcomes between patients whose isolates had MICs above the CART analysis-derived breakpoint versus those with MICs at or below the breakpoint.…”

Tuberculosis

“…They studied a prospective cohort of 144 patients being treated for TB to describe the time course of reduction of bacteria in sputum from patients [4]. The authors showed that the data were best modelled by a bi-exponential decline, confirming the results of studies using serial dilution on solid agar, a time-consuming technique that is difficult to standardise.…”

“…CHIGUTSA et al [4] used the number of days it took for individual patient sputum specimens to become positive in Mycobacteria Growth Indicator Tube (Beckton, Dickinson and Co., Sparks, MA, USA ) as a surrogate for initial organism burden. They studied a prospective cohort of 144 patients being treated for TB to describe the time course of reduction of bacteria in sputum from patients [4].…”

Pharmacologic Considerations in Use and Development of Antituberculosis Drugs

“…However, novel regimens have presented diverse patterns of response, necessitating more flexible approaches capable of capturing and yet comparing these qualitatively different profiles (Diacon et al 2012b). More recently, simple models of elimi-nation fitted to liquid culture data have been developed (Martineau et al 2011;Chigutsa et al 2013). Changes in time to positivity in MGIT (Mycobacteria Growth Indicator Tube) appear to be similar in magnitude and variability to those observed with colony counting (Diacon et al 2010b).…”