Abstract |
Trovafloxacin is a potentially useful agent for treatment of infections caused by cephalosporin-resistant Streptococcus pneumoniae. We studied the effectiveness of trovafloxacin therapy and examined the correlation between pharmacodynamic indices in serum and lung, and bacterial killing. Immunocompetent Balb/c mice were infected by intranasal inoculation of a cephalosporin-resistant S. pneumoniae isolate (MIC of ceftriaxone and trovafloxacin 2 and 0.06 mg/L, respectively). Trovafloxacin 10-30 mg/kg/day in one or three divided doses was started 15 h after infection. Serum and lung drug concentrations were measured at multiple time points for 24 h. Serum concentrations peaked at 30-60 min and lung concentrations approximately 30 min later. The serum T1/2 was approximately 9 h and lung T1/2 varied from 5 to 9 h. Lung AUC and Cmax values were 2-3 times greater than those in serum. At the start of therapy lung bacterial concentrations were 8.4 +/- 0.3 log10 cfu/mL and 24 h later had decreased by 3.5 +/- 0.2, 4.0 +/- 0.2, 0.8 +/- 0.3 and 1.0 +/- 1.2 log10 cfu/mL with 30 mg/kg x 1, 10 mg/kg x 3, 10 mg/kg x 1 and 3.3 mg/kg x 3 regimens, respectively. Although the larger dosages were more effective (P < 0.001) the differences between divided and single dosage regimens were not significant. Trovafloxacin serum AUC/MIC ratio correlated best with bacterial killing in the lungs over 24 h. Trovafloxacin is likely to be useful in the treatment of cephalosporin-resistant S. pneumoniae pneumonia.
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Authors | W Ng, I Lutsar, L Wubbel, F Ghaffar, H Jafri, G H McCracken, I R Friedland |
Journal | The Journal of antimicrobial chemotherapy
(J Antimicrob Chemother)
Vol. 43
Issue 6
Pg. 811-6
(Jun 1999)
ISSN: 0305-7453 [Print] England |
PMID | 10404320
(Publication Type: Journal Article)
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Chemical References |
- Anti-Infective Agents
- Cephalosporins
- Fluoroquinolones
- Naphthyridines
- trovafloxacin
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Topics |
- Analysis of Variance
- Animals
- Anti-Infective Agents
(blood, pharmacokinetics, pharmacology, therapeutic use)
- Cephalosporin Resistance
(physiology)
- Cephalosporins
- Disease Models, Animal
- Female
- Fluoroquinolones
- Lung
(metabolism, microbiology)
- Mice
- Mice, Inbred BALB C
- Microbial Sensitivity Tests
- Naphthyridines
(blood, pharmacokinetics, pharmacology, therapeutic use)
- Pneumonia, Pneumococcal
(blood, drug therapy)
- Streptococcus pneumoniae
(drug effects)
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