Low or high doses of cefquinome targeting low or high bacterial inocula cure Klebsiella pneumoniae lung infections but differentially impact the levels of antibiotic resistance in fecal flora
العنوان: | Low or high doses of cefquinome targeting low or high bacterial inocula cure Klebsiella pneumoniae lung infections but differentially impact the levels of antibiotic resistance in fecal flora |
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المؤلفون: | Maleck V. Vasseur, Agnès Perrin-Guyomard, Pierre-Louis Toutain, Aude A. Ferran, Jérôme Henri, Alain Bousquet-Mélou, Jean-Guy Rolland, Michel Laurentie |
المساهمون: | Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Physiologie et Toxicologie Expérimentales, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA) |
المصدر: | Antimicrobial Agents and Chemotherapy Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2014, 58 (3), pp.1744-8. ⟨10.1128/AAC.02135-13⟩ |
بيانات النشر: | HAL CCSD, 2014. |
سنة النشر: | 2014 |
مصطلحات موضوعية: | Male, antibiotic resistance, medicine.drug_class, Klebsiella pneumoniae, Cephalosporin, Cefquinome, Biology, Gut flora, flore, Microbiology, antibiotique, flora, Antibiotic resistance, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Drug Resistance, Bacterial, medicine, Pneumonia, Bacterial, Animals, Pharmacology (medical), Experimental Therapeutics, résistance, Feces, 2. Zero hunger, Pharmacology, biology.organism_classification, Antimicrobial, Virology, Enterobacteriaceae, Bacterial Load, 3. Good health, Anti-Bacterial Agents, Cephalosporins, Klebsiella Infections, Rats, klebsiella pneumoniae, Infectious Diseases, feces, fecal, medicine.drug, cefquinome |
الوصف: | The combination of efficacious treatment against bacterial infections and mitigation of antibiotic resistance amplification in gut microbiota is a major challenge for antimicrobial therapy in food-producing animals. In rats, we evaluated the impact of cefquinome, a fourth-generation cephalosporin, on both Klebsiella pneumoniae lung infection and intestinal flora harboring CTX-M-producing Enterobacteriaceae . Germfree rats received a fecal flora specimen from specific-pathogen-free pigs, to which a CTX-M-producing Escherichia coli strain had been added. K. pneumoniae cells were inoculated in the lungs of these gnotobiotic rats by using either a low (10 5 CFU) or a high (10 9 CFU) inoculum. Without treatment, all animals infected with the low or high K. pneumoniae inoculum developed pneumonia and died before 120 h postchallenge. In the treated groups, the low-inoculum rats received a 4-day treatment of 5 mg/kg of body weight cefquinome beginning at 24 h postchallenge (prepatent phase of the disease), and the high-inoculum rats received a 4-day treatment of 50 mg/kg cefquinome beginning when the animals expressed clinical signs of infection (patent phase of the disease). The dose of 50 mg/kg targeting the high K. pneumoniae inoculum cured all the treated rats and resulted in a massive amplification of CTX-M-producing Enterobacteriaceae . A dose of 5 mg/kg targeting the low K. pneumoniae inoculum cured all the rats and averted an outbreak of clinical disease, all without any amplification of CTX-M-producing Enterobacteriaceae . These findings might have implications for the development of new antimicrobial treatment strategies that ensure a cure for bacterial infections while avoiding the amplification of resistance genes of human concern in the gut microbiota of food-producing animals. |
اللغة: | English |
تدمد: | 0066-4804 1098-6596 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::64999fcc966d9d8dc61b349025177aa8 https://hal-anses.archives-ouvertes.fr/hal-00978511 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....64999fcc966d9d8dc61b349025177aa8 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 00664804 10986596 |
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