Assuntos
Antibacterianos/farmacologia , Portador Sadio/microbiologia , Farmacorresistência Bacteriana , Lipoglicopeptídeos/farmacologia , Mucosa Nasal/microbiologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Administração Intravenosa , Antibacterianos/administração & dosagem , Método Duplo-Cego , Humanos , Lipoglicopeptídeos/administração & dosagem , Testes de Sensibilidade Microbiana , Staphylococcus aureus/isolamento & purificaçãoRESUMO
Gram-positive bacterial pathogens isolated from patient specimens submitted to 15 Canadian hospital laboratories from 2011 to 2015 were tested in the coordinating laboratory for susceptibility to oritavancin and comparative antimicrobial agents using the Clinical and Laboratory Standards Institute M07-A10 (2015) broth microdilution method. Oritavancin's in vitro activity was equivalent to, or more potent than, vancomycin, daptomycin, linezolid, and tigecycline against methicillin-susceptible Staphylococcus aureus (n=2680; oritavancin MIC90, 0.12µg/mL; 99.9% oritavancin-susceptible), methicillin-resistant S. aureus (n=728; oritavancin MIC90, 0.12µg/mL; 99.7% oritavancin-susceptible), Streptococcus pyogenes (n=218; oritavancin MIC90, 0.25µg/mL; 100% oritavancin-susceptible), Streptococcus agalactiae (n=269; oritavancin MIC90, 0.12µg/mL; 100% oritavancin-susceptible), and vancomycin-susceptible Enterococcus faecalis (n=508; oritavancin MIC90, 0.06µg/mL; 100% oritavancin-susceptible). Oritavancin, dalbavancin, and telavancin demonstrated equivalent in vitro activities (MIC90, µg/mL) against 602 isolates of MSSA (0.06, 0.06, 0.06, respectively) and 144 isolates of MRSA (0.12, 0.06, 0.06, respectively) collected in 2015.
Assuntos
Antibacterianos/uso terapêutico , Glicopeptídeos/uso terapêutico , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Canadá , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Laboratórios Hospitalares , Lipoglicopeptídeos , Testes de Sensibilidade Microbiana/métodosRESUMO
As therapeutic agents of choice in the treatment of complicated infections, glycopeptide antibiotics are often preferentially used in cases of osteomyelitis, an infection located in bone and notoriously difficult to successfully manage. Yet frequent and heavy doses of these systemically administered antibiotics are conventionally prescribed to obtain higher antibiotic levels in the bone and reduce the high recurrence rates. Targeting antibiotics to the bone after systemic administration would present at least three potential advantages: (i) greater efficacy, by concentrating the therapeutic agent in bone; (ii) greater convenience, through a reduction in the frequency of administration; and (iii) greater safety, by reducing the levels of systemic drug exposure. We present here the design, synthesis and in vitro evaluation of eight prodrugs of the glycopeptide antibacterial agents vancomycin and oritavancin taking advantage of the affinity of the bisphosphonate group for bone for delivery to osseous tissues.