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In vitro time-kill studies of oritavancin against clinical isolates of Streptococcus pyogenes

Abstract number: P1855

McKay G.A., Beaulieu S., Sarmiento I., Arhin F.F., Parr Jr. T.R., Moeck G.

Objectives: Oritavancin (ORI), a semi synthetic lipoglycopeptide, exerts bactericidal activity against drug-resistant Gram-positive bacteria. To characterise ORI activity in vitro we performed time-kill (TK) experiments against recent clinical isolates of S. pyogenes, including erythromycin (ERY)-resistant isolates.

Methods: 11 strains of S. pyogenes were tested in TK assays based on CLSI guidelines. To insure quantitative recovery of ORI, assays included 0.002% polysorbate-80 throughout. ORI and commonly recommended antibiotics for the treatment of S. pyogenes complicated skin and skin structure infections (penicillin G [PEN] and ERY) were tested alongside comparators vancomycin (VAN), teicoplanin (TEI), linezolid (LIN) and daptomycin (DAP) at fixed concentrations approximating their free peak (fCmax) and free trough levels in plasma when administered at standard doses taking into account serum protein binding. Cell counts were determined by serial dilution plating.

Results: ORI showed rapid concentration-dependent killing of all strains: when tested at its fCmax, ORI displayed bactericidal activity (geqslant R: gt-or-equal, slanted3 log kill relative to starting inoculum) against ERY-susceptible S. pyogenes (n = 8) between 5 min to 3 h while for ERY-resistant strains (n = 3) ORI was bactericidal by between 30 min and 3 h. When tested at its free trough concentration, ORI demonstrated geqslant R: gt-or-equal, slanted3 log kill within 5 h, regardless of ERY susceptibility status. Against all tested strains, ORI was significantly more rapidly bactericidal than VAN, ERY, PEN, TEI, LIN or DAP each at physiologically-relevant concentration.

Conclusions: The concentration-dependent killing of S. pyogenes by ORI in vitro was independent of ERY susceptibility status of the clinical isolates. These data support the conclusion that ORI displays rapid, concentration-dependent bactericidal activity against recent S. pyogenes isolates and is effective against drug-resistant isolates of S. pyogenes.

Session Details

Date: 16/05/2009
Time: 00:00-00:00
Session name: 19th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Helsinki, Finland, 16 - 19 May 2009
Presentation type:
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