JAC Advance Access originally published online on January 28, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 665-669
© 2003 The British Society for Antimicrobial Chemotherapy
Experimental pneumococcal pleural empyema model: the effect of moxifloxacin
1 Infectious Diseases Unit and 2 Pathology Department, Sheba Medical Center, Sackler School of Medicine, Tel-Hashomer 52621, Israel
Received 27 March 2002; returned 16 September 2002; revised 4 November 2002; accepted 15 November 2002
Objectives: Pleural empyema is a serious complication of pneumonia, the optimal therapy of which is still unknown. The objective of this study was to evaluate the use of moxifloxacin in this condition.
Methods: Pleural empyema was induced in rabbits by intrapleural administration of Pasteurella multocida (105–6 cfu) or turpentine (0.3 mL) followed 3 h later by instillation of Streptococcus pneumoniae (ATCC 49619) (106 cfu) into the pleural cavity. The MICs of moxifloxacin for S. pneumoniae and P. multocida were 0.4 and 0.05 mg/L, respectively. Starting 30 h following S. pneumoniae challenge intramuscular moxifloxacin 12.5 and 25 mg/kg was administered x 4 (every 12 h). Pleural empyema fluid samples were obtained for bacterial count at 12 h intervals following the first three moxifloxacin administrations. Moxifloxacin levels in pleural empyema and serum samples were obtained at 0, 30, 60, 120, 240, 360 and 480 min and 12 h after the 4th dose and determined by bioassay.
Results: In control animals, S. pneumoniae (and P. multocida) persisted in the pleural empyema. S. pneumoniae also persisted in the pleural empyema fluid when moxifloxacin was administered at 12.5 mg/kg (x4 administrations). Mean serum and pleural empyema peak moxifloxacin levels (following the 25 mg/kg dose) were 7.6 (±3.2) and 4.8 (±2.5) mg/L, respectively. Pleural empyema peak moxifloxacin concentration lagged 1 h after serum moxifloxacin. Serum and pleural empyema half-lives were 
1.5 and 6 h, respectively. Serum AUC1–12 was 29.4 (±6.8) mg·h/L and serum area under the inhibitory concentration curve (AUIC) was 73.5 mg·h/L. Pleural empyema AUC1–12 was 34.3 (±11.7) mg/L and pleural empyema AUIC was 85.8 mg·h/L. S. pneumoniae was eradicated from pleural empyema following a single dose of moxifloxacin 25 mg/kg in 52% of the animals and in 96% following four doses. Moxifloxacin was also effective in eradication of P. multocida. The rate of pleural empyema sterilization was related to moxifloxacin serum AUIC (r = 0.82) as well as serum peak moxifloxacin level (r = 0.84), but not to pleural empyema AUIC (r = 0.19) or pleural empyema peak levels. The results were similar for both methods of induction of pleural empyema.
Conclusions: Moxifloxacin appears to penetrate well into experimental pleural empyema and effectively sterilize it from S. pneumoniae. Sterilization of S. pneumoniae is related to serum AUIC rather than to moxifloxacin pharmacokinetics in pleural empyema.
Keywords: moxifloxacin, Pasteurella multocida, pleural empyema, Streptococcus pneumoniae, turpentine
* Corresponding author. Tel: +972-3-5303500; Fax: +972-3-5347081; E-mail: starahil{at}post.tau.ac.il
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