Use of Animal Models To Support Revising Meningococcal Breakpoints of β-Lactams
| Autor: | Ana Antunes, Eva Hong, Aude Terrade, Muhamed-Kheir Taha, Nouria Belkacem, Ala-Eddine Deghmane |
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| Přispěvatelé: | Centre National de Référence des Méningocoques et Haemophilus influenzae - National Reference Center Meningococci and Haemophilus influenzae (CNR), Institut Pasteur [Paris], The work was supported by the Institut Pasteur., This work used the dynamic imaging facilities of the Imagopole at the Institut Pasteur, Paris, France., Institut Pasteur [Paris] (IP) |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Antibiotics MESH: Penicillin G Neisseria meningitidis MESH: Meningococcal Infections medicine.disease_cause Mice β lactams polycyclic compounds MESH: Animals Pharmacology (medical) chemistry.chemical_classification MESH: Microbial Sensitivity Tests Strain (chemistry) Transferrin Penicillin G Liter MESH: Amoxicillin 3. Good health Infectious Diseases MESH: Complement Factor H Complement Factor H Female MESH: Transferrin medicine.drug MESH: Mice Transgenic medicine.drug_class 030106 microbiology Mice Transgenic Microbial Sensitivity Tests Biology MESH: Neisseria meningitidis Microbiology 03 medical and health sciences medicine Animals Humans MESH: Mice Pharmacology MESH: Humans Interleukin-6 Amoxicillin MESH: Interleukin-6 [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Meningococcal Infections Penicillin chemistry Susceptibility MESH: Female |
| Zdroj: | Antimicrobial Agents and Chemotherapy Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2016, 60 (7), pp.4023-4027. ⟨10.1128/AAC.00378-16⟩ Antimicrobial Agents and Chemotherapy, 2016, 60 (7), pp.4023-4027. ⟨10.1128/AAC.00378-16⟩ |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.00378-16 |
| Popis: | Antibiotic susceptibility testing (AST) in Neisseria meningitidis is an important part of the management of invasive meningococcal disease. It defines MICs of antibiotics that are used in treatment and/or prophylaxis and that mainly belong to the beta-lactams. The interpretation of the AST results requires breakpoints to classify the isolates into susceptible, intermediate, or resistant. The resistance to penicillin G is defined by a MIC of >0.25 mg/liter, and that of amoxicillin is defined by a MIC of >1 mg/liter. We provide data that may support revision of resistance breakpoints for beta-lactams in meningococci. We used experimental intraperitoneal infection in 8-week-old transgenic female mice expressing human transferrin and human factor H. Dynamic bioluminescence imaging was performed to follow the infection by bioluminescent meningococcus strains with different MICs. Three hours later, infected mice were treated intramuscularly using several doses of amoxicillin or penicillin G. Signal decreased during infection with a meningococcus strain showing a penicillin G MIC of 0.064 mg/liter at all doses. Signals decreased for the strain with a penicillin G MIC of 0.5 mg/liter only after treatment with the highest doses, corresponding to 250,000 units/kg of penicillin G or 200 mg/kg of amoxicillin, although this decrease was at a lower rate than that of the strain with a MIC of 0.064 mg/liter. The decrease in bioluminescent signals was associated with a decrease in the levels of the proinflammatory cytokine interleukin-6 (IL-6). Our data suggest that a high dose of amoxicillin or penicillin G can reduce growth during infection by isolates showing penicillin G MICs of >0.25 mg/liter and ≤1 mg/liter. |
| Databáze: | OpenAIRE |
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