TY - JOUR
T1 - Systematic analysis of hollow fiber model of tuberculosis experiments
AU - Pasipanodya, Jotam G.
AU - Nuermberger, Eric
AU - Romero, Klaus
AU - Hanna, Debra
AU - Gumbo, Tawanda
N1 - Publisher Copyright:
© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
PY - 2015
Y1 - 2015
N2 - Background. The in vitro hollow fiber system model of tuberculosis (HFS-TB), in tandem with Monte Carlo experiments, was introduced more than a decade ago. Since then, it has been used to perform a large number of tuberculosis pharmacokinetics/pharmacodynamics (PK/PD) studies that have not been subjected to systematic analysis. Methods. We performed a literature search to identify all HFS-TB experiments published between 1 January 2000 and 31 December 2012. There was no exclusion of articles by language. Bias minimization was according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Steps for reporting systematic reviews were followed. Results. There were 22 HFS-TB studies published, of which 12 were combination therapy studies and 10 were monotherapy studies. There were 4 stand-alone Monte Carlo experiments that utilized quantitative output from the HFS-TB. All experiments reported drug pharmacokinetics, which recapitulated those encountered in humans. HFS-TB studies included log-phase growth studies under ambient air, semidormant bacteria at pH 5.8, and nonreplicating persisters at low oxygen tension of ≤10 parts per billion. The studies identified antibiotic exposures associated with optimal kill of Mycobacterium tuberculosis and suppression of acquired drug resistance (ADR) and informed predictions about optimal clinical doses, expected performance of standard doses and regimens in patients, and expected rates of ADR, as well as a proposal of new susceptibility breakpoints. Conclusions. The HFS-TB model offers the ability to perform PK/PD studies including humanlike drug exposures, to identify bactericidal and sterilizing effect rates, and to identify exposures associated with suppression of drug resistance. Because of the ability to perform repetitive sampling from the same unit over time, the HFS-TB vastly improves statistical power and facilitates the execution of time-to-event analyses and repeated event analyses, as well as dynamic system pharmacology mathematical models.
AB - Background. The in vitro hollow fiber system model of tuberculosis (HFS-TB), in tandem with Monte Carlo experiments, was introduced more than a decade ago. Since then, it has been used to perform a large number of tuberculosis pharmacokinetics/pharmacodynamics (PK/PD) studies that have not been subjected to systematic analysis. Methods. We performed a literature search to identify all HFS-TB experiments published between 1 January 2000 and 31 December 2012. There was no exclusion of articles by language. Bias minimization was according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Steps for reporting systematic reviews were followed. Results. There were 22 HFS-TB studies published, of which 12 were combination therapy studies and 10 were monotherapy studies. There were 4 stand-alone Monte Carlo experiments that utilized quantitative output from the HFS-TB. All experiments reported drug pharmacokinetics, which recapitulated those encountered in humans. HFS-TB studies included log-phase growth studies under ambient air, semidormant bacteria at pH 5.8, and nonreplicating persisters at low oxygen tension of ≤10 parts per billion. The studies identified antibiotic exposures associated with optimal kill of Mycobacterium tuberculosis and suppression of acquired drug resistance (ADR) and informed predictions about optimal clinical doses, expected performance of standard doses and regimens in patients, and expected rates of ADR, as well as a proposal of new susceptibility breakpoints. Conclusions. The HFS-TB model offers the ability to perform PK/PD studies including humanlike drug exposures, to identify bactericidal and sterilizing effect rates, and to identify exposures associated with suppression of drug resistance. Because of the ability to perform repetitive sampling from the same unit over time, the HFS-TB vastly improves statistical power and facilitates the execution of time-to-event analyses and repeated event analyses, as well as dynamic system pharmacology mathematical models.
KW - Hollow fiber system;
KW - Monte Carlo experiments
KW - PK/PD;
KW - Quantitative drug development tool;
KW - Tuberculosis;
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U2 - 10.1093/cid/civ425
DO - 10.1093/cid/civ425
M3 - Article
C2 - 26224767
AN - SCOPUS:84942084271
VL - 61
SP - S10-S17
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
ER -