PET/CT imaging reveals a therapeutic response to oxazolidinones in macaques and humans with tuberculosis.
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Auteurs : M Teresa Coleman [États-Unis] ; Ray Y. Chen [États-Unis] ; Myungsun Lee [Corée du Sud] ; Philana Ling Lin [États-Unis] ; Lori E. Dodd [États-Unis] ; Pauline Maiello [États-Unis] ; Laura E. Via [États-Unis] ; Youngran Kim [Corée du Sud] ; Gwendolyn Marriner [États-Unis] ; Veronique Dartois [États-Unis] ; Charles Scanga [États-Unis] ; Christopher Janssen [États-Unis] ; Jing Wang [États-Unis] ; Edwin Klein [États-Unis] ; Sang Nae Cho [Corée du Sud] ; Clifton E. Barry [Afrique du Sud] ; Joanne L. Flynn [États-Unis]Source :
- Science translational medicine [ 1946-6242 ] ; 2014.
Descripteurs français
- KwdFr :
- Acétamides (administration et posologie), Algorithmes, Animaux, Antibactériens (usage thérapeutique), Cellules souches, Fluorodésoxyglucose F18, Humains, Imagerie multimodale, Linézolide, Macaca, Noeuds lymphatiques (anatomopathologie), Oxazolidinones (administration et posologie), Oxazolidinones (usage thérapeutique), Résultat thérapeutique, Tomodensitométrie, Tomographie par émission de positons, Tuberculose ultrarésistante aux médicaments (imagerie diagnostique), Tuberculose ultrarésistante aux médicaments (traitement médicamenteux).
- MESH :
- administration et posologie : Acétamides, Oxazolidinones.
- anatomopathologie : Noeuds lymphatiques.
- imagerie diagnostique : Tuberculose ultrarésistante aux médicaments.
- traitement médicamenteux : Tuberculose ultrarésistante aux médicaments.
- usage thérapeutique : Antibactériens, Oxazolidinones.
- Algorithmes, Animaux, Cellules souches, Fluorodésoxyglucose F18, Humains, Imagerie multimodale, Linézolide, Macaca, Résultat thérapeutique, Tomodensitométrie, Tomographie par émission de positons.
English descriptors
- KwdEn :
- Acetamides (administration & dosage), Algorithms, Animals, Anti-Bacterial Agents (therapeutic use), Extensively Drug-Resistant Tuberculosis (diagnostic imaging), Extensively Drug-Resistant Tuberculosis (drug therapy), Fluorodeoxyglucose F18, Humans, Linezolid, Lymph Nodes (pathology), Macaca, Multimodal Imaging, Oxazolidinones (administration & dosage), Oxazolidinones (therapeutic use), Positron-Emission Tomography, Stem Cells, Tomography, X-Ray Computed, Treatment Outcome.
- MESH :
- chemical , administration & dosage : Acetamides, Oxazolidinones.
- chemical , therapeutic use : Anti-Bacterial Agents, Oxazolidinones.
- diagnostic imaging : Extensively Drug-Resistant Tuberculosis.
- drug therapy : Extensively Drug-Resistant Tuberculosis.
- pathology : Lymph Nodes.
- Algorithms, Animals, Fluorodeoxyglucose F18, Humans, Linezolid, Macaca, Multimodal Imaging, Positron-Emission Tomography, Stem Cells, Tomography, X-Ray Computed, Treatment Outcome.
Abstract
Oxazolidinone antibiotics such as linezolid have shown significant therapeutic effects in patients with extensively drug-resistant (XDR) tuberculosis (TB) despite modest effects in rodents and no demonstrable early bactericidal activity in human phase 2 trials. We show that monotherapy with either linezolid or AZD5847, a second-generation oxazolidinone, reduced bacterial load at necropsy in Mycobacterium tuberculosis-infected cynomolgus macaques with active TB. This effect coincided with a decline in 2-deoxy-2-[(18)F]-fluoro-d-glucose positron emission tomography (FDG PET) imaging avidity in the lungs of these animals and with reductions in pulmonary pathology measured by serial computed tomography (CT) scans over 2 months of monotherapy. In a parallel phase 2 clinical study of linezolid in patients infected with XDR-TB, we also collected PET/CT imaging data from subjects receiving linezolid that had been added to their failing treatment regimens. Quantitative comparisons of PET/CT imaging changes in these human subjects were similar in magnitude to those observed in macaques, demonstrating that the therapeutic effect of these oxazolidinones can be reproduced in this model of experimental chemotherapy. PET/CT imaging may be useful as an early quantitative measure of drug efficacy against TB in human patients.
DOI: 10.1126/scitranslmed.3009500
PubMed: 25473035
Affiliations:
- Afrique du Sud, Corée du Sud, États-Unis
- Maryland, New Jersey, Pennsylvanie, Région capitale de Séoul
- Pittsburgh, Séoul
- Université de Pittsburgh
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last="Dartois">Veronique Dartois</name><affiliation wicri:level="2"><nlm:affiliation>Public Health Research Institute Center, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Research Institute Center, Rutgers New Jersey Medical School, Newark, NJ 07103</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Scanga, Charles" sort="Scanga, Charles" uniqKey="Scanga C" first="Charles" last="Scanga">Charles Scanga</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Janssen, Christopher" sort="Janssen, Christopher" uniqKey="Janssen C" first="Christopher" last="Janssen">Christopher Janssen</name><affiliation wicri:level="4"><nlm:affiliation>Division of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, PA 15260, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Wang, Jing" sort="Wang, Jing" uniqKey="Wang J" first="Jing" last="Wang">Jing Wang</name><affiliation wicri:level="2"><nlm:affiliation>Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Klein, Edwin" sort="Klein, Edwin" uniqKey="Klein E" first="Edwin" last="Klein">Edwin Klein</name><affiliation wicri:level="4"><nlm:affiliation>Division of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, PA 15260, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Cho, Sang Nae" sort="Cho, Sang Nae" uniqKey="Cho S" first="Sang Nae" last="Cho">Sang Nae Cho</name><affiliation wicri:level="1"><nlm:affiliation>International Tuberculosis Research Center, Changwon 631-710, Republic of Korea. Department of Microbiology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>International Tuberculosis Research Center, Changwon 631-710, Republic of Korea. Department of Microbiology, Yonsei University College of Medicine, Seoul 120-752</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Barry, Clifton E" sort="Barry, Clifton E" uniqKey="Barry C" first="Clifton E" last="Barry">Clifton E. Barry</name><affiliation wicri:level="1"><nlm:affiliation>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Institute of Infectious Disease and Molecular Medicine, and the Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Rondebosch 7701, South Africa. cbarry@niaid.nih.gov joanne@pitt.edu.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Institute of Infectious Disease and Molecular Medicine, and the Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Rondebosch 7701</wicri:regionArea><wicri:noRegion>Rondebosch 7701</wicri:noRegion></affiliation></author><author><name sortKey="Flynn, Joanne L" sort="Flynn, Joanne L" uniqKey="Flynn J" first="Joanne L" last="Flynn">Joanne L. Flynn</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA. cbarry@niaid.nih.gov joanne@pitt.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:25473035</idno><idno type="pmid">25473035</idno><idno type="doi">10.1126/scitranslmed.3009500</idno><idno type="wicri:Area/PubMed/Corpus">000B64</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000B64</idno><idno type="wicri:Area/PubMed/Curation">000B64</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000B64</idno><idno type="wicri:Area/PubMed/Checkpoint">000B64</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000B64</idno><idno type="wicri:Area/Ncbi/Merge">004266</idno><idno type="wicri:Area/Ncbi/Curation">004266</idno><idno type="wicri:Area/Ncbi/Checkpoint">004266</idno><idno type="wicri:Area/Main/Merge">001D56</idno><idno type="wicri:Area/Main/Curation">001C80</idno><idno type="wicri:Area/Main/Exploration">001C80</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">PET/CT imaging reveals a therapeutic response to oxazolidinones in macaques and humans with tuberculosis.</title><author><name sortKey="Coleman, M Teresa" sort="Coleman, M Teresa" uniqKey="Coleman M" first="M Teresa" last="Coleman">M Teresa Coleman</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Chen, Ray Y" sort="Chen, Ray Y" uniqKey="Chen R" first="Ray Y" last="Chen">Ray Y. Chen</name><affiliation wicri:level="2"><nlm:affiliation>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Lee, Myungsun" sort="Lee, Myungsun" uniqKey="Lee M" first="Myungsun" last="Lee">Myungsun Lee</name><affiliation wicri:level="1"><nlm:affiliation>International Tuberculosis Research Center, Changwon 631-710, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>International Tuberculosis Research Center, Changwon 631-710</wicri:regionArea><wicri:noRegion>Changwon 631-710</wicri:noRegion></affiliation></author><author><name sortKey="Lin, Philana Ling" sort="Lin, Philana Ling" uniqKey="Lin P" first="Philana Ling" last="Lin">Philana Ling Lin</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA 15260, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Dodd, Lori E" sort="Dodd, Lori E" uniqKey="Dodd L" first="Lori E" last="Dodd">Lori E. Dodd</name><affiliation wicri:level="2"><nlm:affiliation>Biostatistics Research Branch, NIAID, NIH, Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Biostatistics Research Branch, NIAID, NIH, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Maiello, Pauline" sort="Maiello, Pauline" uniqKey="Maiello P" first="Pauline" last="Maiello">Pauline Maiello</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Via, Laura E" sort="Via, Laura E" uniqKey="Via L" first="Laura E" last="Via">Laura E. Via</name><affiliation wicri:level="2"><nlm:affiliation>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Kim, Youngran" sort="Kim, Youngran" uniqKey="Kim Y" first="Youngran" last="Kim">Youngran Kim</name><affiliation wicri:level="1"><nlm:affiliation>International Tuberculosis Research Center, Changwon 631-710, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>International Tuberculosis Research Center, Changwon 631-710</wicri:regionArea><wicri:noRegion>Changwon 631-710</wicri:noRegion></affiliation></author><author><name sortKey="Marriner, Gwendolyn" sort="Marriner, Gwendolyn" uniqKey="Marriner G" first="Gwendolyn" last="Marriner">Gwendolyn Marriner</name><affiliation wicri:level="2"><nlm:affiliation>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Dartois, Veronique" sort="Dartois, Veronique" uniqKey="Dartois V" first="Veronique" last="Dartois">Veronique Dartois</name><affiliation wicri:level="2"><nlm:affiliation>Public Health Research Institute Center, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Research Institute Center, Rutgers New Jersey Medical School, Newark, NJ 07103</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Scanga, Charles" sort="Scanga, Charles" uniqKey="Scanga C" first="Charles" last="Scanga">Charles Scanga</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Janssen, Christopher" sort="Janssen, Christopher" uniqKey="Janssen C" first="Christopher" last="Janssen">Christopher Janssen</name><affiliation wicri:level="4"><nlm:affiliation>Division of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, PA 15260, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Wang, Jing" sort="Wang, Jing" uniqKey="Wang J" first="Jing" last="Wang">Jing Wang</name><affiliation wicri:level="2"><nlm:affiliation>Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Klein, Edwin" sort="Klein, Edwin" uniqKey="Klein E" first="Edwin" last="Klein">Edwin Klein</name><affiliation wicri:level="4"><nlm:affiliation>Division of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, PA 15260, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Cho, Sang Nae" sort="Cho, Sang Nae" uniqKey="Cho S" first="Sang Nae" last="Cho">Sang Nae Cho</name><affiliation wicri:level="1"><nlm:affiliation>International Tuberculosis Research Center, Changwon 631-710, Republic of Korea. Department of Microbiology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>International Tuberculosis Research Center, Changwon 631-710, Republic of Korea. Department of Microbiology, Yonsei University College of Medicine, Seoul 120-752</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Barry, Clifton E" sort="Barry, Clifton E" uniqKey="Barry C" first="Clifton E" last="Barry">Clifton E. Barry</name><affiliation wicri:level="1"><nlm:affiliation>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Institute of Infectious Disease and Molecular Medicine, and the Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Rondebosch 7701, South Africa. cbarry@niaid.nih.gov joanne@pitt.edu.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Institute of Infectious Disease and Molecular Medicine, and the Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Rondebosch 7701</wicri:regionArea><wicri:noRegion>Rondebosch 7701</wicri:noRegion></affiliation></author><author><name sortKey="Flynn, Joanne L" sort="Flynn, Joanne L" uniqKey="Flynn J" first="Joanne L" last="Flynn">Joanne L. Flynn</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA. cbarry@niaid.nih.gov joanne@pitt.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author></analytic><series><title level="j">Science translational medicine</title><idno type="eISSN">1946-6242</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acetamides (administration & dosage)</term><term>Algorithms</term><term>Animals</term><term>Anti-Bacterial Agents (therapeutic use)</term><term>Extensively Drug-Resistant Tuberculosis (diagnostic imaging)</term><term>Extensively Drug-Resistant Tuberculosis (drug therapy)</term><term>Fluorodeoxyglucose F18</term><term>Humans</term><term>Linezolid</term><term>Lymph Nodes (pathology)</term><term>Macaca</term><term>Multimodal Imaging</term><term>Oxazolidinones (administration & dosage)</term><term>Oxazolidinones (therapeutic use)</term><term>Positron-Emission Tomography</term><term>Stem Cells</term><term>Tomography, X-Ray Computed</term><term>Treatment Outcome</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acétamides (administration et posologie)</term><term>Algorithmes</term><term>Animaux</term><term>Antibactériens (usage thérapeutique)</term><term>Cellules souches</term><term>Fluorodésoxyglucose F18</term><term>Humains</term><term>Imagerie multimodale</term><term>Linézolide</term><term>Macaca</term><term>Noeuds lymphatiques (anatomopathologie)</term><term>Oxazolidinones (administration et posologie)</term><term>Oxazolidinones (usage thérapeutique)</term><term>Résultat thérapeutique</term><term>Tomodensitométrie</term><term>Tomographie par émission de positons</term><term>Tuberculose ultrarésistante aux médicaments (imagerie diagnostique)</term><term>Tuberculose ultrarésistante aux médicaments (traitement médicamenteux)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Acetamides</term><term>Oxazolidinones</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Anti-Bacterial Agents</term><term>Oxazolidinones</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Acétamides</term><term>Oxazolidinones</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Noeuds lymphatiques</term></keywords><keywords scheme="MESH" qualifier="diagnostic imaging" xml:lang="en"><term>Extensively Drug-Resistant Tuberculosis</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Extensively Drug-Resistant Tuberculosis</term></keywords><keywords scheme="MESH" qualifier="imagerie diagnostique" xml:lang="fr"><term>Tuberculose ultrarésistante aux médicaments</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lymph Nodes</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Tuberculose ultrarésistante aux médicaments</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antibactériens</term><term>Oxazolidinones</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Algorithms</term><term>Animals</term><term>Fluorodeoxyglucose F18</term><term>Humans</term><term>Linezolid</term><term>Macaca</term><term>Multimodal Imaging</term><term>Positron-Emission Tomography</term><term>Stem Cells</term><term>Tomography, X-Ray Computed</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Algorithmes</term><term>Animaux</term><term>Cellules souches</term><term>Fluorodésoxyglucose F18</term><term>Humains</term><term>Imagerie multimodale</term><term>Linézolide</term><term>Macaca</term><term>Résultat thérapeutique</term><term>Tomodensitométrie</term><term>Tomographie par émission de positons</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Oxazolidinone antibiotics such as linezolid have shown significant therapeutic effects in patients with extensively drug-resistant (XDR) tuberculosis (TB) despite modest effects in rodents and no demonstrable early bactericidal activity in human phase 2 trials. We show that monotherapy with either linezolid or AZD5847, a second-generation oxazolidinone, reduced bacterial load at necropsy in Mycobacterium tuberculosis-infected cynomolgus macaques with active TB. This effect coincided with a decline in 2-deoxy-2-[(18)F]-fluoro-d-glucose positron emission tomography (FDG PET) imaging avidity in the lungs of these animals and with reductions in pulmonary pathology measured by serial computed tomography (CT) scans over 2 months of monotherapy. In a parallel phase 2 clinical study of linezolid in patients infected with XDR-TB, we also collected PET/CT imaging data from subjects receiving linezolid that had been added to their failing treatment regimens. Quantitative comparisons of PET/CT imaging changes in these human subjects were similar in magnitude to those observed in macaques, demonstrating that the therapeutic effect of these oxazolidinones can be reproduced in this model of experimental chemotherapy. PET/CT imaging may be useful as an early quantitative measure of drug efficacy against TB in human patients.</div></front></TEI><affiliations><list><country><li>Afrique du Sud</li><li>Corée du Sud</li><li>États-Unis</li></country><region><li>Maryland</li><li>New Jersey</li><li>Pennsylvanie</li><li>Région capitale de Séoul</li></region><settlement><li>Pittsburgh</li><li>Séoul</li></settlement><orgName><li>Université de Pittsburgh</li></orgName></list><tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Coleman, M Teresa" sort="Coleman, M Teresa" uniqKey="Coleman M" first="M Teresa" last="Coleman">M Teresa Coleman</name></region><name sortKey="Chen, Ray Y" sort="Chen, Ray Y" uniqKey="Chen R" first="Ray Y" last="Chen">Ray Y. Chen</name><name sortKey="Dartois, Veronique" sort="Dartois, Veronique" uniqKey="Dartois V" first="Veronique" last="Dartois">Veronique Dartois</name><name sortKey="Dodd, Lori E" sort="Dodd, Lori E" uniqKey="Dodd L" first="Lori E" last="Dodd">Lori E. Dodd</name><name sortKey="Flynn, Joanne L" sort="Flynn, Joanne L" uniqKey="Flynn J" first="Joanne L" last="Flynn">Joanne L. Flynn</name><name sortKey="Janssen, Christopher" sort="Janssen, Christopher" uniqKey="Janssen C" first="Christopher" last="Janssen">Christopher Janssen</name><name sortKey="Klein, Edwin" sort="Klein, Edwin" uniqKey="Klein E" first="Edwin" last="Klein">Edwin Klein</name><name sortKey="Lin, Philana Ling" sort="Lin, Philana Ling" uniqKey="Lin P" first="Philana Ling" last="Lin">Philana Ling Lin</name><name sortKey="Maiello, Pauline" sort="Maiello, Pauline" uniqKey="Maiello P" first="Pauline" last="Maiello">Pauline Maiello</name><name sortKey="Marriner, Gwendolyn" sort="Marriner, Gwendolyn" uniqKey="Marriner G" first="Gwendolyn" last="Marriner">Gwendolyn Marriner</name><name sortKey="Scanga, Charles" sort="Scanga, Charles" uniqKey="Scanga C" first="Charles" last="Scanga">Charles Scanga</name><name sortKey="Via, Laura E" sort="Via, Laura E" uniqKey="Via L" first="Laura E" last="Via">Laura E. Via</name><name sortKey="Wang, Jing" sort="Wang, Jing" uniqKey="Wang J" first="Jing" last="Wang">Jing Wang</name></country><country name="Corée du Sud"><noRegion><name sortKey="Lee, Myungsun" sort="Lee, Myungsun" uniqKey="Lee M" first="Myungsun" last="Lee">Myungsun Lee</name></noRegion><name sortKey="Cho, Sang Nae" sort="Cho, Sang Nae" uniqKey="Cho S" first="Sang Nae" last="Cho">Sang Nae Cho</name><name sortKey="Kim, Youngran" sort="Kim, Youngran" uniqKey="Kim Y" first="Youngran" last="Kim">Youngran Kim</name></country><country name="Afrique du Sud"><noRegion><name sortKey="Barry, Clifton E" sort="Barry, Clifton E" uniqKey="Barry C" first="Clifton E" last="Barry">Clifton E. Barry</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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