JAC Advance Access published online on January 28, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg094
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Infectious Diseases Unit, Sheba Medical Center, Sackler School of Medicine,
Tel-Hashomer 52621, Israel
* Corresponding author. E-mail: starahil{at}post.tau.ac.il.
Received 27 March 2002
; revised 16 September 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 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
Experimental pneumococcal pleural empyema model:
the effect of moxifloxacin
2 Pathology Department,
Sheba Medical Center, Sackler School of Medicine,
Tel-Hashomer 52621, Israel
3 Infectious Diseases Unit, Sheba Medical Center, Sackler School of Medicine,
Tel-Hashomer 52621, Israel
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.
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