Pharmacokinetic/pharmacodynamic assessment of the in-vivo efficacy of imipenem alone or in combination with amikacin for the treatment of experimental multiresistant Acinetobacter baumannii pneumonia
| Autor: | J. Ibáñez-Martínez, María Eugenia Pachón-Ibáñez, Máximo Bernabeu-Wittel, Jerónimo Pachón, C. Pichardo, A. García-Curiel, Manuel E. Jiménez-Mejías |
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| Rok vydání: | 2005 |
| Předmět: |
Microbiology (medical)
Acinetobacter baumannii Imipenem medicine.drug_class Antibiotics Guinea Pigs Cmax Microbial Sensitivity Tests Pharmacology Microbiology Pharmacokinetics Drug Resistance Multiple Bacterial pharmacodynamics polycyclic compounds medicine Pneumonia Bacterial Animals Amikacin Lung Antibacterial agent biology business.industry Drug Synergism General Medicine biochemical phenomena metabolism and nutrition bacterial infections and mycoses biology.organism_classification experimental pneumonia Anti-Bacterial Agents Disease Models Animal Infectious Diseases Pharmacodynamics Drug Therapy Combination Female business pharmacokinetics medicine.drug Acinetobacter Infections |
| Zdroj: | Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 11(4) |
| ISSN: | 1198-743X |
| Popis: | A guinea-pig pneumonia model involving imipenem-susceptible and imipenem-resistant strains of Acinetobacter baumannii was developed to assess the in-vitro and in-vivo activities of imipenem, alone or in combination with amikacin, and the pharmacokinetic and pharmacodynamic parameters. Serum levels were measured by bioassay (imipenem) or immunoassay (amikacin), followed by calculation of pharmacokinetic and pharmacodynamic parameters (Cmax, AUC, t1/2, Cmax/MIC, AUC/MIC, and Δt /MIC). In-vivo efficacy was evaluated by comparing bacterial counts in the lungs of treatment groups with end-of-therapy controls by anova and post-hoc tests. Decreases in the Cmax (13.4%), AUC (13%), t1/2 (25%) and Δt/MIC (11.8–32.2%) of imipenem were observed when it was administered with amikacin, compared with administration of imipenem alone. Similarly, decreases in the Cmax (34.5%), AUC (11.6%), Cmax/MIC (34.5%) and AUC/MIC (11.7%) of amikacin were observed when it was administered with imipenem. Bacterial counts in lungs were reduced by imipenem (p 0.004) with the imipenem-susceptible strain, and by amikacin (p 0.001) with the imipenem-resistant strain. The combination of imipenem plus amikacin was inferior to imipenem alone with the imipenem-susceptible strain (p 0.01), despite their in-vitro synergy, and was inferior to amikacin alone with the imipenem-resistant strain (p < 0.0001). In summary, combined use of imipenem with amikacin was less efficacious than monotherapy, probably because of a drug–drug interaction that resulted in decreased pharmacokinetic and pharmacodynamic parameters for both antimicrobial agents. |
| Databáze: | OpenAIRE |
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