Jotam G Pasipanodya1, Eric Nuermberger2, Klaus Romero3, Debra Hanna3, Tawanda Gumbo4. 1. Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas. 2. Center for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland. 3. Critical Path Institute, Tucson, Arizona. 4. Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas Department of Medicine, University of Cape Town, Observatory, South Africa.
Abstract
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.
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.
Authors: Sander P van Rijn; Shashikant Srivastava; Mireille A Wessels; Dick van Soolingen; Jan-Willem C Alffenaar; Tawanda Gumbo Journal: Antimicrob Agents Chemother Date: 2017-08-24 Impact factor: 5.191
Authors: Devyani Deshpande; Jan-Willem C Alffenaar; Claudio U Köser; Keertan Dheda; Moti L Chapagain; Noviana Simbar; Thomas Schön; Marieke G G Sturkenboom; Helen McIlleron; Pooi S Lee; Thearith Koeuth; Stellah G Mpagama; Sayera Banu; Suporn Foongladda; Oleg Ogarkov; Suporn Pholwat; Eric R Houpt; Scott K Heysell; Tawanda Gumbo Journal: Clin Infect Dis Date: 2018-11-28 Impact factor: 9.079
Authors: Devyani Deshpande; Jotam G Pasipanodya; Stellah G Mpagama; Paula Bendet; Shashikant Srivastava; Thearith Koeuth; Pooi S Lee; Sujata M Bhavnani; Paul G Ambrose; Guy Thwaites; Scott K Heysell; Tawanda Gumbo Journal: Clin Infect Dis Date: 2018-11-28 Impact factor: 9.079
Authors: Jin Wu; Fred Racine; Michael K Wismer; Katherine Young; Donna M Carr; Jing C Xiao; Ravi Katwaru; Qian Si; Paul Harradine; Mary Motyl; Pratik R Bhagunde; Matthew L Rizk Journal: Antimicrob Agents Chemother Date: 2018-04-26 Impact factor: 5.191
Authors: Beatriz E Ferro; Shashikant Srivastava; Devyani Deshpande; Jotam G Pasipanodya; Dick van Soolingen; Johan W Mouton; Jakko van Ingen; Tawanda Gumbo Journal: Antimicrob Agents Chemother Date: 2016-05-23 Impact factor: 5.191
Authors: Beatriz E Ferro; Shashikant Srivastava; Devyani Deshpande; Carleton M Sherman; Jotam G Pasipanodya; Dick van Soolingen; Johan W Mouton; Jakko van Ingen; Tawanda Gumbo Journal: Antimicrob Agents Chemother Date: 2015-12-07 Impact factor: 5.191