Levofloxacin-rifampin combination is highly bactericidal in experimental methicillin-susceptible Staphylococcus aureus prosthetic joint infection
Abstract number: 1733_1279
Muller-Serieys C., Saleh Mghir A., Massias L., Andremont A., Fantin B.
Objectives:Staphylococcus aureus is the most common pathogen responsible for bacterial joint infections. Levofloxacin (LEV) and rifampin (RIF) are highly active in vitro against susceptible strains of MSSA; nevertheless no data are available on the in vivo relevance of this combination for treating MSSA prosthetic joint infection.
Methods: A partial knee replacement was performed in rabbits with a silicone implant fitting into the intramedullary canal of the tibia, and 107 CFU of a MSSA strain (MICs and MPCs: 0.125 and 1 mg/L for LEV and ≤ 0.016 and 256 mg/L for RIF, respectively) were injected into the knees. Treatment was started 7 days after inoculation and lasted for 7 days. Infected animals were randomly assigned to: either no Rx (controls), or LEV (25 mg/kg IV b.i.d.), or RIF (10 mg/kg IM b.i.d.) or LEV+RIF. Surviving bacteria were counted in bone 2 days after the end of Rx, and resistant mutants were detected on antibiotic-containing agar.
Results: LEV AUC was comparable to that achieved in human after a 750 mg daily dose. The mean log10 CFU/g of bone were significantly reduced with LEV (2.92 ± 1.33, 5/12 sterile animals) and RIF (3.20 ± 2.12, 5/11 sterile animals) versus controls (6.36 ± 1.33, 0/10 sterile animals) (p < 0.05). RIF+LEV combination (mean log10 CFU/g of bone: 1.99 ± 0.52, 6/12 sterile animals) was significantly more effective than RIF alone (p < 0.05) and prevented the emergence of RIF-resistant mutants as observed in 4/6 positive bones in RIF treated animals and 2/6 controls. No LEV-resistant mutants were detected in any group of animals.
Conclusion: In this MSSA joint prosthesis infection, LEV combined with RIF was highly bactericidal and prevented the selection of mutant resistant to RIF. LEV+RIF should be of interest for treating MSSA prothetic joint infection in human.
|Session name:||European Society of Clinical Microbiology and Infectious Diseases|
|Location:||ICC, Munich, Germany|
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