Characterization of Differentially Detectable Mycobacterium tuberculosis in the Sputum of Subjects with Drug-Sensitive or Drug-Resistant Tuberculosis before and after Two Months of Therapy.

TitleCharacterization of Differentially Detectable Mycobacterium tuberculosis in the Sputum of Subjects with Drug-Sensitive or Drug-Resistant Tuberculosis before and after Two Months of Therapy.
Publication TypeJournal Article
Year of Publication2021
AuthorsZainabadi K, Walsh KFrances, Vilbrun SCharles, Mathurin LDaniel, Lee MHee, Saito K, Mishra S, Ocheretina O, Pape JWilliam, Nathan C, Fitzgerald DW
JournalAntimicrob Agents Chemother
Volume65
Issue8
Paginatione0060821
Date Published2021 Jul 16
ISSN1098-6596
KeywordsAntitubercular Agents, Humans, Mycobacterium tuberculosis, Pharmaceutical Preparations, Sputum, Tuberculosis, Multidrug-Resistant, Tuberculosis, Pulmonary
Abstract

Standard methods for enumerating Mycobacterium tuberculosis in patient sputum can miss large populations of viable M. tuberculosis cells that are unable to grow either on solid medium or in liquid medium unless the medium has been extensively diluted. Because these bacteria can be detected in liquid medium after limiting dilution, they have been termed differentially culturable or differentially detectable M. tuberculosis (DD-Mtb). Treatment with isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) (HRZE) for 1 to 2 weeks has been shown to increase the representation of DD-Mtb in the sputum of drug-sensitive (DS) tuberculosis (TB) patients. However, little is known about DD-Mtb after longer periods of treatment with HRZE or in patients with drug-resistant (DR) TB who receive second-line therapies. Here, we measured the proportion of DD-Mtb cells in the sputum of 47 subjects, 29 with DS TB and 18 with DR TB, before initiation of treatment and at 2 weeks and 2 months thereafter. Prior to treatment, DD-Mtb cells represented the majority of M. tuberculosis cells in the sputum of 21% of subjects with DS TB, and this proportion rose to 65% after 2 weeks of treatment with first-line drugs. In subjects with DR TB, DD-Mtb cells were found in the sputum of 29% of subjects prior to treatment initiation, and this proportion remained steady at 31% after 2 weeks of treatment with second-line drugs. By 2 months, DD-Mtb cells were detected in the sputum of only 2/15 (13.3%) subjects with DS TB and in 0/15 of subjects with DR TB. One of the DS subjects whose sputum was positive for DD-Mtb at month 2 later experienced treatment failure.

DOI10.1128/AAC.00608-21
Alternate JournalAntimicrob Agents Chemother
PubMed ID34060896
PubMed Central IDPMC8284451
Grant ListU19 AI111143 / AI / NIAID NIH HHS / United States
UM1 AI069421 / AI / NIAID NIH HHS / United States
K24AI098627 / / HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /
D43 TW009337 / TW / FIC NIH HHS / United States
U19 AI162568 / AI / NIAID NIH HHS / United States
U01 AI069421 / AI / NIAID NIH HHS / United States
D43 TW010062 / TW / FIC NIH HHS / United States
U19AI111143 / / HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /
K08 AI139360 / AI / NIAID NIH HHS / United States
K24 AI098627 / AI / NIAID NIH HHS / United States

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