Pharmacokinetic-Pharmacodynamic Target Attainment Analyses To Evaluate In Vitro Susceptibility Test Interpretive Criteria for Ceftaroline against Staphylococcus aureus and Streptococcus pneumoniae
| Autor: | H. David Friedland, Christopher M. Rubino, Scott A. Van Wart, Sujata M. Bhavnani, Ian A. Critchley, Todd Riccobene, Tatiana Khariton, Paul G. Ambrose |
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| Rok vydání: | 2014 |
| Předmět: |
Staphylococcus aureus
medicine.medical_specialty medicine.drug_class Population Cephalosporin Microbial Sensitivity Tests medicine.disease_cause Severity of Illness Index Gastroenterology Microbiology Mice Internal medicine Severity of illness Streptococcus pneumoniae medicine Animals Humans Ceftaroline fosamil Pharmacology (medical) Dosing Renal Insufficiency Chronic education Pharmacology Clinical Trials as Topic education.field_of_study Models Statistical business.industry Liter Anti-Bacterial Agents Cephalosporins Infectious Diseases Susceptibility business Monte Carlo Method medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 58:885-891 |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | To provide support for in vitro susceptibility test interpretive criteria decisions for ceftaroline against Staphylococcus aureus and Streptococcus pneumoniae , as well as dose adjustment recommendations for renal impairment, pharmacokinetic-pharmacodynamic (PK-PD) target attainment was evaluated for simulated patients administered intravenous (i.v.) ceftaroline fosamil at 600 mg twice daily (q12h) and simulated patients with renal impairment administered various dosing regimens. Using a previously developed population PK model, Monte Carlo simulation was used to generate ceftaroline plasma concentration profiles for simulated patients with normal renal function or mild, moderate, or severe renal impairment. Using these profiles, the percentage of time during the dosing interval that free-drug concentrations remained above the MIC ( f % T >MIC) for ceftaroline at steady state was calculated. Percentages of simulated patients achieving f % T >MIC targets for S. aureus and S. pneumoniae based on murine infection models were calculated by MIC. At MICs of 2 mg/liter for S. aureus and 1 mg/liter for S. pneumoniae , the percentages of simulated patients with normal renal function and mild renal impairment following administration of ceftaroline fosamil at 600 mg q12h, moderate renal impairment following administration of ceftaroline fosamil at 400 mg q12h, and severe renal impairment following administration of ceftaroline fosamil at 300 mg q12h achieving f % T >MIC targets (≥26 for S. aureus and ≥44 for S. pneumoniae ) exceeded 90%. The results of these analyses, which suggested that in vitro susceptibility test interpretive criteria defining susceptible could be as high as MICs of ≤2 and ≤1 mg/liter for ceftaroline against S. aureus and S. pneumoniae , respectively, provide support for current FDA and CLSI criteria, which define susceptible as MICs of 1 and 0.5 mg/liter, respectively. Recommendations for dose adjustments for patients with renal impairment were also supported by the results of these analyses. |
| Databáze: | OpenAIRE |
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