Journal of Antimicrobial Chemotherapy (1999) 43, 811-816
© 1999 The British Society for Antimicrobial Chemotherapy
Pharmacodynamics of trovafloxacin in a mouse model of cephalosporin-resistant Streptococcus pneumoniae pneumonia
The University of Texas Southwestern Medical Center, Dallas, TX 75235, USA
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. pneumoniaeisolate (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.
* Corresponding address. Department of Paediatrics, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899. Tel: +65-293-7933; Fax: +65-394-1043
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