Pharmacokinetic-Pharmacodynamic Evaluation of Ertapenem for Patients with Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia
| Autor: | Elizabeth A Lakota, Helio S. Sader, Paul G. Ambrose, Justin C Bader, Sujata M. Bhavnani, John H. Rex, Glenn E. Dale |
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| Rok vydání: | 2019 |
| Předmět: |
Ertapenem
medicine.medical_specialty Klebsiella pneumoniae Population Microbial Sensitivity Tests Clinical Therapeutics medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Pneumonia Bacterial Humans Medicine Pharmacology (medical) 030212 general & internal medicine education Pharmacology 0303 health sciences education.field_of_study Bacteria biology 030306 microbiology business.industry Pseudomonas aeruginosa Bacterial pneumonia Pneumonia Ventilator-Associated Antimicrobial medicine.disease biology.organism_classification Anti-Bacterial Agents Infectious Diseases chemistry Staphylococcus aureus Pharmacodynamics business |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 63 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.00318-19 |
| Popis: | Ertapenem provides activity against many pathogens commonly associated with hospital-acquired and ventilator-associated bacterial pneumoniae (HABP and VABP, respectively), including methicillin-susceptible Staphylococcus aureus and numerous Gram-negative pathogens with one major gap in coverage, Pseudomonas aeruginosa. Pharmacokinetic-pharmacodynamic (PK-PD) target attainment analyses were conducted to evaluate ertapenem against the most prevalent Enterobacteriaceae causing HABP/VABP. The objective of these analyses was to provide dose selection support for and demonstrate the appropriateness of ertapenem to empirically treat patients with HABP/VABP when administered with murepavadin, a novel targeted antimicrobial exhibiting a highly specific spectrum of activity against P. aeruginosa. A previously developed population pharmacokinetic model, a total-drug epithelial lining fluid (ELF) to free-drug serum penetration ratio, contemporary in vitro surveillance data for ertapenem against Enterobacteriaceae, and percentage of the dosing interval for which drug concentrations exceed the MIC value (%T>MIC) targets associated with efficacy were used to conduct Monte Carlo simulations for five ertapenem regimens administered over short or prolonged durations of infusion. Overall total-drug ELF percent probabilities of PK-PD target attainment based on a %T>MIC target of 35% among simulated patients with HABP/VABP arising from Enterobacteriaceae based on pathogen prevalence data for nosocomial pneumonia ranged from 89.1 to 92.7% for all five ertapenem regimens evaluated. Total-drug ELF percent probabilities of PK-PD target attainment ranged from 99.8 to 100%, 97.9 to 100%, 10.6 to 74.1%, and 0 to 1.50% at MIC values of 0.06, 0.12, 1, and 4 μg/ml, respectively (MIC(90) values for Escherichia coli, Serratia marcescens, Enterobacter species, and Klebsiella pneumoniae, respectively). Results of these analyses provide support for the evaluation of ertapenem in combination with murepavadin for the treatment of patients with HABP/VABP. |
| Databáze: | OpenAIRE |
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