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Antibiotic levels in empyemic pleural fluid
L R Teixeira1, S A Sasse, M A Villarino
1Pulmonary Disease Program, Saint Thomas Hospital and Vanderbilt University, Nashville, TN 37202, USA.
Objective:
To determine the degree to which bioactive penicillin, metronidazole, ceftriaxone, clindamycin, vancomycin, and gentamicin penetrate into empyemic pleural fluid using our new rabbit model of empyema.
Methods:
An empyema was created via the intrapleural injection of 10(8)()Pasteurella multocida bacteria into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, penicillin, 24,000 U/kg; metronidazole, 37 mg/kg; ceftriaxone, 30 mg/kg; clindamycin, 9 mg/kg; vancomycin, 15 mg/kg; or gentamicin, 1 mg/kg, were administered IV. Antibiotic levels in samples of pleural fluid and serum, collected serially for up to 480 min, were then determined using a bioassay.
Results:
The degree to which the different antibiotics penetrated into the infected pleural space was highly variable. Penicillin penetrated most easily, followed by metronidazole, ceftriaxone, clindamycin, vancomycin, and gentamicin. Of the antibiotics tested, penicillin and metronidazole equilibrated the most rapidly with the infected pleural fluid. Penicillin levels remained elevated in pleural fluid even after serum levels had decreased.
Conclusions:
Using this rabbit model of empyema, there was marked variation in the penetration of antibiotics into the empyemic fluid. Although there are species differences between rabbit and human pleura, the variance in degree of penetration of antibiotics into the pleural space should be considered when antibiotics are selected for the treatment of patients with empyema.
Insights
Antibiotic penetration into empyemic pleural fluid varied significantly in a rabbit model. Penicillin and metronidazole showed the best penetration, informing clinical treatment decisions for empyema.
Area of Science:
- Pharmacology
- Infectious Diseases
- Animal Models
Background:
- Empyema, a serious infection of the pleural space, requires effective antibiotic therapy.
- Understanding antibiotic penetration into infected pleural fluid is crucial for successful treatment outcomes.
Purpose of the Study:
- To evaluate the penetration of several key antibiotics into empyemic pleural fluid.
- To compare the efficacy of penicillin, metronidazole, ceftriaxone, clindamycin, vancomycin, and gentamicin in a rabbit empyema model.
Main Methods:
- Empyema was induced in New Zealand white rabbits by intrapleural injection of Pasteurella multocida.
- Antibiotics were administered intravenously after empyema confirmation.
- Pleural fluid and serum antibiotic levels were measured over time using a bioassay.
Main Results:
- Significant variability was observed in antibiotic penetration into empyemic pleural fluid.
- Penicillin demonstrated the highest and most rapid penetration, followed by metronidazole.
- Penicillin and metronidazole achieved the quickest equilibration, with penicillin levels remaining elevated in pleural fluid longer than serum levels.
Conclusions:
- The study highlights marked variations in antibiotic penetration into empyemic fluid in a rabbit model.
- These findings suggest that antibiotic selection for human empyema should consider the differential penetration into the pleural space, despite species differences.