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Efficacy of levofloxacin alone and in combination with rifampin in staphylococcal experimental foreign-body infection

Abstract number: P1912

Murillo O., Pachón M.E., Euba G., Verdaguer R., Tubau F., Cabellos C., Cabo J., Gudiol F., Ariza J.

Objectives: Since levofloxacin at high doses (LHD) was more active than at conventional doses (LCD) and was the best therapy alone in a rat-model of foreign-body infection (FBI) by Staphylococcus aureus (Sa), we tested how these differences affect in the activity of their respective combinations with rifampin (R) in vitro and in vivo.

Methods: In vitro studies. MICs and MBCs (mg/L) of Sa ATCC 29213 were respectively: 0.5, 1 (levofloxacin) and 0.015, 0.12 (R). 24 h kill-curves (KC) were performed in the log- (LP) and the stationary-phase (SP). Animal studies. Two Teflon tissue-cages with 2 cover-slips (CV) each were implanted in rats; after 3 weeks, tissue-cage fluid (TCF) was infected with Sa and, 3 weeks later, therapy was administered for 7 days (7dT) in all cases and prolonged to 14 days (14dT) for LHD alone and with R. Therapeutic groups (mg.kg/h): LHD (100/24; PD values equivalent to human ones for 1000 mg/d), LCD (50/24; PD equivalent to 500 mg/d), LHD+R (25/12), LCD+R and controls (C). Criteria of efficacy: (i) differences in TCF bacterial counts between the beginning and the end of treatment (Dlog UFC/ml); (ii) bacterial counts in CV at the end of 14 dT. The presence of levofloxacin- or R-resistant strains was screened.

Results: KC in LP showed antagonism with all combinations of levofloxacin at concentrations geqslant R: gt-or-equal, slanted1 mg/L and R. KC in SP showed indifference with the combination of peak concentrations of LCD (4 mg/L)+R and tend to antagonism with LHD (12 mg/L)+R. The Dlog UFC/ml at the end of 7dT were (n): LHD -2.08 (50), LCD -1.24 (20), LHD+R -1.55 (44), LCD+R -1.51 (20) and C 0.33 (22); all groups were better than C (p < 0.05, T-test), LHD was the best therapy (P < 0.03 vs LHD+R, P < 0.01 vs LCD). At the end of 14dT the Dlog UFC/ml in TCF were (n) LHD -3.84 (21), LHD+R -3.37 (21) and C 0.40 (15), and bacterial counts in CV (logCFU/ml) were 2.24 (LHD), 3.36 (LHD+R) and 5.4 (C); both groups were significantly better than C and LHD better than LHD+R (P < 0.03) in CV. No resistant strains were detected in either group at the end of 7dT and 14dT.

Conclusions. LHD confirmed the great efficacy against FBI by Sa, it was the best treatment and no resistant strains appeared. The addition of R to LHD showed antagonism effect; the clinical relevance of these findings should be further evaluated. In contrast, if R is going to be used, the dose of levofloxacin did not contribute significantly to the efficacy of the combination and both doses protect against resistance.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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