Antibiotic levels in empyemic pleural fluid.
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.
Teixeira
L R
LR
Pulmonary Disease Program, Saint Thomas Hospital and Vanderbilt University, Nashville, TN 37202, USA.
Sasse
S A
SA
Villarino
M A
MA
Nguyen
T
T
Mulligan
M E
ME
Light
R W
RW
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002443:Ceftriaxone / Q000008:administration & dosage / Q000493:pharmacokinetics; D002981:Clindamycin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D016724:Empyema, Pleural / Q000188:drug therapy / Q000378:metabolism*; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D007262:Infusions, Intravenous; D008795:Metronidazole / Q000008:administration & dosage / Q000493:pharmacokinetics; D010326:Pasteurella Infections / Q000188:drug therapy / Q000378:metabolism*; D016979:Pasteurella multocida; D010406:Penicillins / Q000008:administration & dosage / Q000493:pharmacokinetics; D011817:Rabbits; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D010406:Penicillins; D008795:Metronidazole; D002981:Clindamycin; D014640:Vancomycin; D002443:Ceftriaxone