Penetration of clarithromycin in experimental pleural empyema model fluid.
BACKGROUND
The degree of penetration of clarithromycin into the pleural fluid has not been studied.


OBJECTIVE
To determine the degree to which clarithromycin penetrates into empyemic pleural fluid using a new rabbit model of empyema.


METHODS
An empyema was created via the intrapleural injection of 1 ml turpentine followed 24 h later by instillation of 5 ml (10(10)) Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, clarithromycin 30 mg/kg was administered intravenously. Antibiotic levels were determined on samples of pleural fluid and blood samples collected serially over 12 h. Antibiotic levels were estimated using HPLC.


RESULTS
The antibiotic penetrated well into the empyemic pleural fluid (AUC(PF)/AUC(serum) ratio of 1.57). The time to equilibration between the pleural fluid and blood antibiotic levels was 8 h. The peak pleural fluid level (Cmax(PF) of 2.88 microg/ml) occurred 1 h (Tmax(PF) of 1 h) after infusion and decreased thereafter. The Cmax(serum) was 3.53 microg/ml at 1 h after administration.


CONCLUSIONS
The levels of clarithromycin in the pleural fluid after intravenous administration are inhibitory for most of the usual pathogens causing empyema. The degree of penetration of clarithromycin should be considered when macrolides are selected for the treatment of patients with empyema.
Liapakis
I E
IE
2nd Department of Surgery, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
Light
R W
RW
Pitiakoudis
M S
MS
Karayiannakis
A J
AJ
Giamarellos-Bourboulis
E J
EJ
Ismailos
G
G
Anagnostoulis
S
S
Simopoulos
C E
CE
Bouros
D E
DE
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001826:Body Fluids / Q000187:drug effects / Q000378:metabolism; D017291:Clarithromycin / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D016724:Empyema, Pleural / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007262:Infusions, Intravenous; D008297:Male; D010994:Pleura / Q000187:drug effects / Q000473:pathology; D011817:Rabbits; D012016:Reference Values; D012965:Sodium Chloride / Q000008:administration & dosage
D000900:Anti-Bacterial Agents; D012965:Sodium Chloride; D017291:Clarithromycin