In Vitro and In Vivo Synergistic Activities of Linezolid Combined with Subinhibitory Concentrations of Imipenem against Methicillin-Resistant Staphylococcus aureus
AUTOR(ES)
Jacqueline, Cédric
FONTE
American Society for Microbiology
RESUMO
Indifference or moderate antagonism of linezolid combined with other antibiotics in vitro and in vivo have mainly been reported in the literature. We have assessed the in vitro activities of linezolid, alone or in combination with imipenem, against methicillin-resistant Staphylococcus aureus (MRSA) strains using the dynamic checkerboard and time-kill curve methods. Linezolid and low concentrations of imipenem had a synergistic effect, leading us to evaluate the in vivo antibacterial activity of the combination using the rabbit endocarditis experimental model. Two MRSA strains were used for in vivo experiments: one was a heterogeneous glycopeptide-intermediate clinical S. aureus strain isolated from blood cultures, and the other was the S. aureus COL reference strain. Animals infected with one of two MRSA strains were randomly assigned to one of the following treatments: no treatment (controls), linezolid (simulating a dose in humans of 10 mg/kg of body weight every 12 h), a constant intravenous infusion of imipenem (which allowed the steady-state concentration of about 1/32 the MIC of imipenem for each strain to be reached in serum), or the combination of both treatments. Linezolid and imipenem as monotherapies exhibited no bactericidal activity against either strain. The combination of linezolid plus imipenem showed in vivo bactericidal activity that corresponded to a decrease of at least 4.5 log CFU/g of vegetation compared to the counts for the controls. In conclusion, the combination exhibited synergistic and bactericidal activities against two MRSA strains after 5 days of treatment. The combination of linezolid plus imipenem appears to be promising for the treatment of severe MRSA infections and merits further investigations to explore the mechanism underlying the synergy between the two drugs.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=538916Documentos Relacionados
- Subinhibitory concentrations of imipenem induce increased resistance to methicillin and imipenem in vitro in methicillin-resistant Staphylococcus aureus.
- In vitro effects of beta-lactams combined with beta-lactamase inhibitors against methicillin-resistant Staphylococcus aureus.
- Comparison of Linezolid Activities under Aerobic and Anaerobic Conditions against Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococcus faecium
- Comparative in vitro activity of coumermycin against methicillin-resistant Staphylococcus aureus.
- In vitro activities of teichomycin, fusidic acid, flucloxacillin, fosfomycin, and vancomycin against methicillin-resistant Staphylococcus aureus.