biostudies-literatureSrivastava SNIAID NIH HHS1951-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC3209814biostudies-literatureUnknown204(12)<h4>Background</h4>It is believed that nonadherence is the proximate cause of multidrug-resistant tuberculosis (MDR-tuberculosis) emergence. The level of nonadherence associated with emergence of MDR-tuberculosis is unknown. Performance of a randomized controlled trial in which some patients are randomized to nonadherence would be unethical; therefore, other study designs should be utilized.<h4>Methods</h4>We performed hollow fiber studies for both bactericidal and sterilizing effect, with inoculum spiked with 0.5% rifampin- and isoniazid-resistant isogenic strains in some experiments. Standard therapy was administered daily for 28-56 days, with extents of nonadherence varying between 0% and 100%. Sizes of drug-resistant populations were compared using analysis of variance. We also exploreThe Journal of infectious diseasesMultidrug-resistant tuberculosis not due to noncompliance but to between-patient pharmacokinetic variability.PMC3209814R01AI079497R01 AI079497Srivastava SMeek CLeff RPasipanodya JGGumbo TfalseMultidrug-resistant tuberculosis not due to noncompliance but to between-patient pharmacokinetic variability.<h4>Background</h4>It is believed that nonadherence is the proximate cause of multidrug-resistant tuberculosis (MDR-tuberculosis) emergence. The level of nonadherence associated with emergence of MDR-tuberculosis is unknown. Performance of a randomized controlled trial in which some patients are randomized to nonadherence would be unethical; therefore, other study designs should be utilized.<h4>Methods</h4>We performed hollow fiber studies for both bactericidal and sterilizing effect, with inoculum spiked with 0.5% rifampin- and isoniazid-resistant isogenic strains in some experiments. Standard therapy was administered daily for 28-56 days, with extents of nonadherence varying between 0% and 100%. Sizes of drug-resistant populations were compared using analysis of variance. We also explore2011-01-01T00:00:00Z2011 Dec2025-04-04T22:24:06.807Z2019-03-27T00:45:46ZS-EPMC32098142202162410.1093/infdis/jir658