In vitro time-kill studies of oritavancin against drug-resistant isolates of Staphylococcus aureus

Abstract number: P544

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

Background: Oritavancin (ORI), a semi-synthetic lipoglycopeptide, exerts bactericidal activity against Gram-positive bacteria including vancomycin (VAN)-resistant S. aureus and enterococci. To characterise ORI activity in vitro we performed time-kill (TK) experiments against S. aureus of clinical importance, including recent antibiotic-resistant isolates.

Methods: 6 strains of S. aureus (1 meticillin-resistant [MRSA], 1 community-acquired [CA] MRSA, 1 linezolid-resistant MRSA, 1 heterogeneous VAN-intermediate [hVISA], and 2 VAN-resistant [VRSA]) were tested in TK assays based on CLSI guidelines. ORI assays included 0.002% polysorbate-80 throughout. ORI and comparators VAN, teicoplanin (TEI), linezolid (LIN) and daptomycin (DAP) were tested at static concentrations approximating their free peak (fCmax) and free trough in plasma when administered at standard doses. Cell counts were determined by serial dilution plating.

Results: ORI showed concentration-dependent killing of all strains tested: at its fCmax (predicted from a 200 mg dose in humans), ORI displayed bactericidal activity ( 3 log kill relative to starting inoculum) against the MRSA, CA MRSA and linezolid-resistant MRSA within 2 h. Against VRSA, ORI demonstrated 3 log kill relative to starting inoculum within 3 h for VRS2 and 6 h for VRS1. At fCmax, ORI was bactericidal against hVISA at 24 h; at fCmax predicted from an 800 mg dose, ORI achieved 3 log kill by 6 h for this strain.

Conclusions: ORI displayed concentration-dependent killing of MRSA, VRSA, hVISA in vitro. ORI was more rapidly bactericidal against all bacteria tested than were VAN, TEI, LIN or DAP at physiologically-relevant concentrations. These data support the conclusion that ORI displays concentration-dependent bactericidal activity on recent, drug-resistant isolates of S. aureus.