Probability of pharmacodynamic target attainment with standard and prolonged-infusion antibiotic regimens for empiric therapy in adults with hospital-acquired pneumonia.
Abstract | BACKGROUND: The pharmacodynamic characteristics of antibiotics should be considered when choosing empiric dosage regimens for the treatment of pneumonia. OBJECTIVE: This study compared the probabilities of achieving requisite pharmacodynamic exposure (ie, f T > MIC, AUC/MIC) for antibiotics given for the empiric treatment of hospital-acquired pneumonia (HAP) as recommended by the 2005 guidelines of the American Thoracic Society and the Infectious Diseases Society of America. METHODS: In a 5000-patient Monte Carlo simulation, pharmacodynamic analyses were performed for standard doses of cefepime, ceftazidime, ceftriaxone, ciprofloxacin, ertapenem, imipenem, levofloxacin, meropenem, and piperacillin/tazobactam. Prolonged 3-hour infusion regimens were also evaluated for anti-pseudomonal beta-lactams. MIC data were incorporated from the 2007 Meropenem Yearly Susceptibility Test Information Collection, a national surveillance study. The weighted cumulative fraction of response (wCFR) against common pneumonia pathogens was determined for each regimen. A second scenario was conducted by altering the pathogen prevalence to assess wCFR for late-onset pneumonia (ie, HAP in patients with prolonged mechanical ventilation). Optimal wCFR was defined a priori as >or=90%. RESULTS: Among the 0.5-hour infusions, cefepime, ceftazidime, and meropenem had the highest wCFRs (>or=90%) against pathogens that cause HAP ( cefepime, 1 g q8h, 92.8%; 2 g q8h, 97.2%; 2 g q12h, 94.3%; ceftazidime, 2 g q8h, 93.2%; meropenem, 1 g q8h, 90.9%; 2 g q8h, 93.9%). Imipenem (500 mg q6h, 85.5%; 1 g q8h, 88.1%) and piperacillin/tazobactam (4.5 g q6h, 80.5%) as 0.5-hour infusions were nearly optimal, whereas ceftriaxone, ertapenem, and the fluoroquinolones had the lowest wCFR values. All regimens showed lower wCFRs for late-onset pneumonia than for HAP. Optimal wCFRs were found only with prolonged (3-hour) infusions of 2 g q8h for ceftazidime (94.5%) and meropenem (90.1%), whereas cefepime 2 g q8h achieved optimal wCFR with both a 0.5-hour infusion (93.1%) and a 3-hour infusion (95.3%). CONCLUSIONS:
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Authors | Aryun Kim, Joseph L Kuti, David P Nicolau |
Journal | Clinical therapeutics
(Clin Ther)
Vol. 31
Issue 11
Pg. 2765-78
(Nov 2009)
ISSN: 1879-114X [Electronic] United States |
PMID | 20110018
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2009 Excerpta Medica Inc. All rights reserved. |
Chemical References |
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Topics |
- Algorithms
- Anti-Bacterial Agents
(administration & dosage, pharmacokinetics, therapeutic use)
- Area Under Curve
- Computer Simulation
- Cross Infection
(drug therapy, microbiology)
- Dose-Response Relationship, Drug
- Humans
- Infusions, Intravenous
- Metabolic Clearance Rate
- Microbial Sensitivity Tests
- Monte Carlo Method
- Pneumonia, Bacterial
(drug therapy, microbiology)
- Population
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