References 1. Galimand M, Courvalin P, Lambert T. Plasmid-mediated high- level resistance to aminoglycosides in Enterobacteriaceae due to 16S rRNA methylation. Antimicrob Agents Chemother 2003; 47: 2565–71. 2. Doi Y, Arakawa Y. 16S ribosomal RNA methylation: emerging resistance mechanism against aminoglycosides. Clin Infect Dis 2007; 45: 88–94. 3. Bogaerts P, Galimand M, Bauraing C et al. Emergence of ArmA and RmtB aminoglycoside resistance 16S rRNA methylases in Belgium. J Antimicrob Chemother 2007; 59: 459–64. 4. Naas T, Lezzar A, Bentchouala C et al. Multidrug-resistant Salmonella enterica serotype Senftenberg isolates producing CTX-M b-lactamases from Constantine, Algeria. J Antimicrob Chemother 2005; 56: 439–40. 5. Golebiewski M, Kern-Zdanowicz I, Zienkiewicz M et al. Complete nucleotide sequence of the pCTX-M3 plasmid and its involvement in spread of the extended-spectrum b-lactamase gene bla CTX-M-3 . Antimicrob Agents Chemother 2007; 51: 3789–95. 6. Galimand M, Sabtcheva S, Courvalin P et al. Worldwide dissemi- nated armA aminoglycoside resistance methylase gene is borne by composite transposon Tn1548. Antimicrob Agents Chemother 2005; 49: 2949–53. 7. Wu Q, Zhang Y, Han L et al. Plasmid-mediated 16S rRNA methy- lases in aminoglycoside-resistant Enterobacteriaceae isolates in Shanghai, China. Antimicrob Agents Chemother 2009; 53: 271–2. Journal of Antimicrobial Chemotherapy doi:10.1093/jac/dkp286 Advance Access publication 4 August 2009 Comparative in vitro activity of oritavancin against Staphylococcus aureus strains that are resistant, intermediate or heteroresistant to vancomycin Francis F. Arhin*, Ingrid Sarmiento, Thomas R. Parr Jr and Gregory Moeck The Medicines Company, Ville Saint Laurent, Que ´bec, Canada Keywords: glycopeptide non-susceptible, MICs, MBCs *Corresponding author. Tel: þ1 (514) 332-1008, ext. 1700; Fax: þ1 (514) 332-6033; E-mail: francis.arhin@themedco.com Sir, Widespread use of vancomycin has led to the emergence of isolates that show reduced susceptibility to vancomycin; vancomycin-intermediate Staphylococcus aureus (VISA), vancomycin-resistant S. aureus (VRSA) and heteroresistant VISA (hVISA) have been described. 1 The emergence of such strains with concomitant vancomycin therapeutic failures 2 has necessitated the development of other therapeutic agents. Newer drugs of the glycopeptide class, such as oritavancin, with activity against isolates with reduced susceptibility to vanco- mycin are currently in development. Additional mechanisms exhib- ited by oritavancin help explain its rapid, concentration-dependent bactericidal activity in vitro 3 and distinguish it from vancomycin. In surveillance studies, oritavancin activity was demonstrated against vancomycin-susceptible S. aureus isolates that are susceptible and resistant to methicillin. 4 This study examined the in vitro activity of oritavancin against clinical isolates of VRSA, VISA and hVISA using recently updated broth microdi- lution methodology. 5 MICs and MBCs of oritavancin were determined for these groups of organisms and compared with those of seven clinically used antimicrobial agents. MICs of antimicrobial agents were determined by broth microdilution according to CLSI (formerly NCCLS) guidelines. 5 Polysorbate-80 was included when testing oritavancin, so as to limit losses of oritavancin to the surfaces of test vessels as rec- ommended in CLSI guidelines. 5 MBCs were also determined according to CLSI guidelines. 6 Aliquots (50 mL) were plated onto brain heart infusion agar (BHIA) plates for the VISA and hVISA isolates, or BHIA plates containing 4 mg/L vancomycin for the VRSA isolates to main- tain selection for vancomycin, and incubated at 358C for 24 h. The MBC was defined as the lowest concentration killing .99.9% of the original inoculum. 6 Oritavancin showed good in vitro activity against the hVISA isolates (MIC range of 0.12 –2 mg/L and MIC 90 of 1 mg/L; Table 1). The oritavancin MIC 90 was identical to those of line- zolid and quinupristin/dalfopristin, and one doubling dilution higher than that of tigecycline. The oritavancin MIC 90 was 2- to 8-fold lower than those of the rest of the comparators. The orita- vancin MBC range and MBC 90 against hVISAs were 0.25–2 and 1 mg/L, respectively. The oritavancin MBC 90 against the hVISA isolates was identical to that of tigecycline and 2- to 64-fold lower than those of the rest of the comparators. The ori- tavancin MBC 90 /MIC 90 ratio of 1 indicates that oritavancin is bactericidal against hVISA. The oritavancin MBC 90 /MIC 90 ratio was identical to that of daptomycin and 2- to 16-fold lower than those of the rest of the comparators. Oritavancin showed good in vitro activity against the VISA isolates (MIC range of 0.5–4 mg/L and MIC 90 of 2 mg/L; Table 1). The MIC 90 was identical to that of quinupristin/dalfo- pristin and was two doubling dilutions higher than that of tigecy- cline. The oritavancin MIC 90 was 2- to 8-fold lower than those of the rest of the comparators. The oritavancin MBC range and MBC 90 against VISAs were 0.5–8 and 4 mg/L, respectively. The oritavancin MBC 90 for the VISA isolates was 4-fold higher than that of tigecycline and 2- to 8-fold lower than those of the rest of the comparators. The oritavancin MBC 90 /MIC 90 ratio of 2 indicates that oritavancin is bactericidal against VISA. The ori- tavancin MBC 90 /MIC 90 ratio was identical to, or within a dilution of, those of the comparators. Oritavancin showed good in vitro activity against the VRSA isolates (MIC range of 0.12–1 mg/L and MIC 90 of 0.5 mg/L; Table 1). The MIC 90 was identical to that of daptomycin and was a doubling dilution higher than that of tigecycline. The oritavancin MIC 90 was 2- to .1024-fold lower than those of the rest of the comparators. The oritavancin MBC range and MBC 90 against VRSAs were 0.25–1 and 1 mg/L, respectively. The oritavancin MBC 90 for the VRSA isolates was 2- to .512-fold lower than those of the comparators. The oritavancin MBC 90 /MIC 90 ratio of 2 indicates that oritavancin is bactericidal against VRSA. The oritavancin MBC 90 /MIC 90 ratio was at least 2-fold lower than those of the comparators. Against the 35 isolates of S. aureus tested in this study, the oritavancin MIC range and MIC 90 were 0.12–4 and 1 mg/L, respectively (Table 1). The oritavancin MIC 90 was identical to that of quinupristin/dalfopristin and was a doubling dilution Research letters 868 by guest on July 4, 2016 http://jac.oxfordjournals.org/ Downloaded from