Abstract
ObjectiveTo determine the extent of linezolid and ertapenem penetration into the empyemic fluid using a rabbit model of empyema.MethodsAn empyema was created via the intrapleural injection of Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracocentesis, 24 hours post inoculation, linezolid (10 mg/kg) and ertapenem (60 mg/kg) were administered intravenously into 10 and 8 infected empyemic rabbits, respectively. Antibiotic levels were determined in samples of pleural fluid and blood serum, collected serially at 1, 2, 4, 6 and 8 hours, after administration each of the two antibiotics.ResultsLinezolid as well as ertapenem penetrate well into the empyemic pleural fluid, exhibiting a slower onset and decline compared to the corresponding blood serum levels. Equilibration between blood serum and pleural fluid compartments seems to occur at 1.5 hours for both linezolid and ertapenem, with peak pleural fluid levels (Cmaxpf of 2.02 ± 0.73 «mu»g/ml and Cmaxpf of 3.74 ± 1.39 «mu»g/ml, correspondingly) occurring 2 hours post antibiotics administration and decreasing very slowly thereafter. The serum concentrations for both antibiotics were significantly lower from the corresponding pleural fluid ones during the 8 hours collecting data, with the exception of samples collected at the 1st hour (Cmaxserum of 2.1 ± 1.2 «mu»g/ml for linezolid and Cmaxserum of 6.26 ± 2.98 «mu»g/ml for ertapenem).ConclusionPleural fluid levels of both antibiotics are inhibitory for common specified pathogens causing empyema.
Highlights
The annual incidence of bacterial pneumonia is estimated to be 2-4 million in the USA, with approximately 20% of patients requiring hospitalization [1]. Of these patients 40-60% develop parapneumonic pleural effusions and pleural empyemas occur in 5-10% [2]
The area under the concentration versus time curve (AUC) was almost 4-fold higher in the pleural fluid compared to the blood serum compartment
The time to equilibration between the pleural fluid and blood serum compartments seems to occur at 1.5 hours, with an onset of approximately 60% at the first hour compared to the corresponding blood serum levels
Summary
The annual incidence of bacterial pneumonia is estimated to be 2-4 million in the USA, with approximately 20% of patients requiring hospitalization [1]. Of these patients 40-60% develop parapneumonic pleural effusions and pleural empyemas occur in 5-10% [2]. Therapy needs to be initiated as soon as pleural fluid, sputum and blood samples have been taken but with the following in mind: in addition to the specificity of antimicrobial agent for the offending microorganism, its distribution within the body is a critical factor in determining its therapeutic efficacy. Second and third generation cephalosporins, beta-lactam-beta-lactamase inhibitor combinations, fluoroquinolones, metronidazole, clindamycin, meropenem, or aztreonam may be considered [8]
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