Hydroxychloroquine susceptibility determination of Coxiella burnetii in human embryonic lung (HEL) fibroblast cells.
Identifieur interne : 000D15 ( Main/Exploration ); précédent : 000D14; suivant : 000D16Hydroxychloroquine susceptibility determination of Coxiella burnetii in human embryonic lung (HEL) fibroblast cells.
Auteurs : Emmanouil Angelakis [France] ; Jacques Bou Khalil [France] ; Marion Le Bideau [France] ; Celine Perreal [France] ; Bernard La Scola [France] ; Didier Raoult [France]Source :
- International journal of antimicrobial agents [ 1872-7913 ] ; 2017.
Descripteurs français
- KwdFr :
- Adolescent, Adulte, Adulte d'âge moyen, Antibactériens (pharmacologie), Cellules cultivées, Coxiella burnetii (), Doxycycline (pharmacologie), Femelle, Fibroblastes (microbiologie), Humains, Hydroxychloroquine (pharmacologie), Mâle, Sujet âgé, Sujet âgé de 80 ans ou plus, Tests de sensibilité microbienne.
- MESH :
- microbiologie : Fibroblastes.
- pharmacologie : Antibactériens, Doxycycline, Hydroxychloroquine.
- Adolescent, Adulte, Adulte d'âge moyen, Cellules cultivées, Coxiella burnetii, Femelle, Humains, Mâle, Sujet âgé, Sujet âgé de 80 ans ou plus, Tests de sensibilité microbienne.
English descriptors
- KwdEn :
- MESH :
- chemical , pharmacology : Anti-Bacterial Agents, Doxycycline, Hydroxychloroquine.
- drug effects : Coxiella burnetii.
- microbiology : Fibroblasts.
- Adolescent, Adult, Aged, Aged, 80 and over, Cells, Cultured, Female, Humans, Male, Microbial Sensitivity Tests, Middle Aged.
Abstract
Coxiella burnetii, the causative agent of Q fever, survives and replicates in the acidic environment of monocytes/macrophages; hydroxychloroquine, through alkalinisation of the acidic vacuoles, is critical for the management of Q fever. In this study, a collection of C. burnetii strains isolated from human samples was tested to evaluate the in vitro minimum inhibitory concentrations (MICs) of doxycycline and hydroxychloroquine. Serial two-fold dilutions of doxycycline (0.25-8 mg/L) and hydroxychloroquine (0.25-4 mg/L) were added to C. burnetii-infected human embryonic lung (HEL) fibroblast cells after 48 h of incubation, in duplicate. DNA was detected by C. burnetii-specific semi-quantitative PCR with primers and probes designed for amplification of the IS1111 and IS30A spacers. A total of 29 C. burnetii isolates obtained from 29 patients were tested. Doxycycline MICs ranged from 0.25 mg/L to 0.5 mg/L and hydroxychloroquine MICs from 0.25 mg/L to >4 mg/L. Four C. burnetii stains had hydroxychloroquine MICs ≤ 1 mg/L. The concentration of hydroxychloroquine was associated with a significant decrease in C. burnetii DNA copies in HEL cells based on linear regression analysis (P= 0.01). Recommended serum concentrations of hydroxychloroquine significantly reduced the growth of C. burnetii. Moreover, some C. burnetii strains presented hydroxychloroquine MICs below the recommended serum concentrations, indicating that, for these cases, hydroxychloroquine treatment alone may even be effective.
Url:
DOI: 10.1016/j.ijantimicag.2017.02.015
PubMed: 28478211
Affiliations:
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Jean Moulin, 13385 Marseille, France. Electronic address: angelotasmanos@msn.com.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Khalil, Jacques Bou" sort="Khalil, Jacques Bou" uniqKey="Khalil J" first="Jacques Bou" last="Khalil">Jacques Bou Khalil</name><affiliation wicri:level="4"><nlm:affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Le Bideau, Marion" sort="Le Bideau, Marion" uniqKey="Le Bideau M" first="Marion" last="Le Bideau">Marion Le Bideau</name><affiliation wicri:level="4"><nlm:affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Perreal, Celine" sort="Perreal, Celine" uniqKey="Perreal C" first="Celine" last="Perreal">Celine Perreal</name><affiliation wicri:level="4"><nlm:affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="La Scola, Bernard" sort="La Scola, Bernard" uniqKey="La Scola B" first="Bernard" last="La Scola">Bernard La Scola</name><affiliation wicri:level="4"><nlm:affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Raoult, Didier" sort="Raoult, Didier" uniqKey="Raoult D" first="Didier" last="Raoult">Didier Raoult</name><affiliation wicri:level="4"><nlm:affiliation>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Aix-Marseille Université, CNRS-IRD 198 UMR 6236, 27 Bd. Jean Moulin, 13385 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author></analytic><series><title level="j">International journal of antimicrobial agents</title><idno type="eISSN">1872-7913</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Anti-Bacterial Agents (pharmacology)</term><term>Cells, Cultured</term><term>Coxiella burnetii (drug effects)</term><term>Doxycycline (pharmacology)</term><term>Female</term><term>Fibroblasts (microbiology)</term><term>Humans</term><term>Hydroxychloroquine (pharmacology)</term><term>Male</term><term>Microbial Sensitivity Tests</term><term>Middle Aged</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Antibactériens (pharmacologie)</term><term>Cellules cultivées</term><term>Coxiella burnetii ()</term><term>Doxycycline (pharmacologie)</term><term>Femelle</term><term>Fibroblastes (microbiologie)</term><term>Humains</term><term>Hydroxychloroquine (pharmacologie)</term><term>Mâle</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term><term>Tests de sensibilité microbienne</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anti-Bacterial Agents</term><term>Doxycycline</term><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Coxiella burnetii</term></keywords><keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Fibroblastes</term></keywords><keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Fibroblasts</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antibactériens</term><term>Doxycycline</term><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Cells, Cultured</term><term>Female</term><term>Humans</term><term>Male</term><term>Microbial Sensitivity Tests</term><term>Middle Aged</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Cellules cultivées</term><term>Coxiella burnetii</term><term>Femelle</term><term>Humains</term><term>Mâle</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term><term>Tests de sensibilité microbienne</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Coxiella burnetii, the causative agent of Q fever, survives and replicates in the acidic environment of monocytes/macrophages; hydroxychloroquine, through alkalinisation of the acidic vacuoles, is critical for the management of Q fever. In this study, a collection of C. burnetii strains isolated from human samples was tested to evaluate the in vitro minimum inhibitory concentrations (MICs) of doxycycline and hydroxychloroquine. Serial two-fold dilutions of doxycycline (0.25-8 mg/L) and hydroxychloroquine (0.25-4 mg/L) were added to C. burnetii-infected human embryonic lung (HEL) fibroblast cells after 48 h of incubation, in duplicate. DNA was detected by C. burnetii-specific semi-quantitative PCR with primers and probes designed for amplification of the IS1111 and IS30A spacers. A total of 29 C. burnetii isolates obtained from 29 patients were tested. Doxycycline MICs ranged from 0.25 mg/L to 0.5 mg/L and hydroxychloroquine MICs from 0.25 mg/L to >4 mg/L. Four C. burnetii stains had hydroxychloroquine MICs ≤ 1 mg/L. The concentration of hydroxychloroquine was associated with a significant decrease in C. burnetii DNA copies in HEL cells based on linear regression analysis (P= 0.01). Recommended serum concentrations of hydroxychloroquine significantly reduced the growth of C. burnetii. Moreover, some C. burnetii strains presented hydroxychloroquine MICs below the recommended serum concentrations, indicating that, for these cases, hydroxychloroquine treatment alone may even be effective.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Provence-Alpes-Côte d'Azur</li></region><settlement><li>Marseille</li></settlement><orgName><li>Université d'Aix-Marseille</li></orgName></list><tree><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Angelakis, Emmanouil" sort="Angelakis, Emmanouil" uniqKey="Angelakis E" first="Emmanouil" last="Angelakis">Emmanouil Angelakis</name></region><name sortKey="Khalil, Jacques Bou" sort="Khalil, Jacques Bou" uniqKey="Khalil J" first="Jacques Bou" last="Khalil">Jacques Bou Khalil</name><name sortKey="La Scola, Bernard" sort="La Scola, Bernard" uniqKey="La Scola B" first="Bernard" last="La Scola">Bernard La Scola</name><name sortKey="Le Bideau, Marion" sort="Le Bideau, Marion" uniqKey="Le Bideau M" first="Marion" last="Le Bideau">Marion Le Bideau</name><name sortKey="Perreal, Celine" sort="Perreal, Celine" uniqKey="Perreal C" first="Celine" last="Perreal">Celine Perreal</name><name sortKey="Raoult, Didier" sort="Raoult, Didier" uniqKey="Raoult D" first="Didier" last="Raoult">Didier Raoult</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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