oritavancin and Streptococcal-Infections

Oritavancin is a lipoglycopeptide that has been approved for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) caused by susceptible organisms. Oritavancin causes cell death by inhibiting cell wall synthesis as well as depolarising and permeabilising the cellular membrane of Gram-positive pathogens. The activities of oritavancin in comparison with vancomycin, daptomycin and linezolid were determined against a collection of over 11000 recent clinical Gram-positive isolates from patient infections (2011-2014), including skin and skin-structure infections. A total of 7253 Staphylococcus aureus, 839 coagulase-negative staphylococci (CoNS), 1464 enterococci and 1637 β-haemolytic streptococci (βHS) were collected from the USA and Europe. Minimum inhibitory concentrations (MICs) were determined using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methods, and susceptibility was determined using CLSI and US Food and Drug Administration (FDA) (for oritavancin) breakpoint criteria. Equivalent in vitro activity (MIC50/90, 0.015-0.03/0.06 μg/mL) was observed for oritavancin against meticillin-resistant S. aureus (MRSA), meticillin-susceptible S. aureus (MSSA) and Enterococcus faecalis in both regions. Slightly higher oritavancin MICs were obtained against CoNS, Streptococcus agalactiae, Enterococcus faecium (MIC90, 0.12 μg/mL) and against other βHS (MIC90, 0.25 μg/mL). Oritavancin demonstrated comparatively lower MICs than daptomycin and vancomycin when tested against multidrug-resistant S. aureus, vancomycin-resistant enterococci and erythromycin-resistant βHS. Oritavancin exhibited potent in vitro activity against the most common pathogens associated with ABSSSIs in the USA and Europe.

Topics: Anti-Bacterial Agents; Daptomycin; Drug Resistance, Multiple, Bacterial; Enterococcus; Europe; Glycopeptides; Humans; Linezolid; Lipoglycopeptides; Microbial Sensitivity Tests; North America; Skin Diseases, Bacterial; Staphylococcal Infections; Staphylococcus; Streptococcal Infections; Streptococcus; Vancomycin

Topics: Anti-Bacterial Agents; Drug Approval; Glycopeptides; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Organophosphates; Oxazoles; Streptococcal Infections; Teicoplanin; United States; United States Food and Drug Administration

The activity of oritavancin in vitro against recent clinical isolates of Streptococcus pyogenes, including antibiotic-resistant strains, was characterised by determination of broth microdilution minimal inhibitory concentrations as well as time-kill assays. Ten clinical isolates of S. pyogenes, three of which were resistant to erythromycin, as well as one reference S. pyogenes strain were tested. In the time-kill assays, oritavancin and the comparators vancomycin, teicoplanin, linezolid, penicillin, erythromycin and daptomycin were tested at static concentrations approximating their free peak (fC(max)) and free trough (fC(min)) concentrations in plasma when administered at approved doses for skin and skin-structure infections. At its fC(max) predicted from a 200 mg dose in humans, oritavancin exerted bactericidal activity (> or = 3 log kill relative to the starting inoculum) within 15 min to 3 h against all tested strains. Daptomycin exhibited bactericidal activity at its fC(max) for all but one strain; time to cidality was between 15 min and 6 h. At fC(min), only oritavancin was bactericidal against all the tested strains. Oritavancin displayed concentration-dependent killing of all isolates in vitro. Oritavancin was more rapidly bactericidal than the comparators at physiologically relevant concentrations against all strains tested. These data support the potential utility of oritavancin in infections with contemporary isolates of S. pyogenes, including drug-resistant strains.

Topics: Anti-Bacterial Agents; Glycopeptides; Humans; Lipoglycopeptides; Microbial Sensitivity Tests; Microbial Viability; Streptococcal Infections; Streptococcus pyogenes; Time Factors