Safety of Prolonged HighDose Levofloxacin Therapy for Bone Infections
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Safety of Prolonged High-Dose Levofloxacin Therapy for Bone Infections E.SENNEVILLE, J.POISSY, H.MELLIEZ, M.VALETTE, Y.YAZDANPANAH, Y.MOUTON Infectious Diseases Department. Dron Hospital, Tourcoing, France.
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BACKGROUND Fluoroquinolones are the cornerstone for the treatment of osteomyelitis : antibacterial spectrum high bone diffusion rapid bactericidal activity oral biodisponibility Available data for ofloxacin, pefloxacin and ciprofloxacin Lack of data for new F.quinolones such as LVF
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LVF: pharmacokinetic data IV administration of LVX 500 mg results in bone and synovial concentrations greater than breakpoints of many pathogens (Rimmele et al. JAC. 2004) but bactericidal concentrations are not maintained throughout 24 hours: it is necessary to use either twice daily or high dose once a day regimen. (Shirtliff et al. JAC. 2001) Oral biodisponibility is ~100%. Oral and IV routes are considered to be equivalent. (Croom et al. Drugs. 2003)
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LVF: clinical data Experts recommendation: 750 mg qd to 500 mg bid, po. (Zimmerli. NEJM. 2004)
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MATERIAL AND METHODs Retrospective analysis of tolerance and efficacy of LVF in patients treated for bone infections, from January 2001 to February 2004 dosage: = 750mg/day duration: = 28 days follow-up after the end of the treatment: = 28 days Comparison of two regimens 500 mg/12h (group 1; n=41) 500 mg/12h for 3 weeks, then 750 mg once daily (group 2; n=21) 750 mg once daily (group 3; n=22)
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RESULTS (1) Patients n=84 Mean age=52.4 years ± 15.4 Type of bone infection material 46 (54.7%) chronic osteomyelitis 18 (21.4%) diabetic foot osteomyelitis 16 (19.1%) spondylodiscitis 4 (4.8%)
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RESULTS (3) Mean duration of treatment: Parenteral administration during 6 days (5-8) Total = 13.7 weeks (range, 5-24) Rifampicin was associated with LVF in 62patients (73.8%) Median follow-up after the end of treatment = 15.1 months (range, 12-30)
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RESULTS (4): side effects * Treatment stopped because of diarrhoea
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RESULTS (5): myalgia
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CONCLUSIONS Long term and high dose therapeutic LVF-containing regimens seem to be appropriate for treatment of bone infections, including those with orthopaedic material A dosage of 750mg once daily LVX may be warranted for bone infections rather than 500mg bid for the entire duration of therapy or for the first 3 weeks Our results need to be confirmed by clinical trials including larger cohorts of patients
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