P785 In vitro activitiy of dalbavancin against clinical vancomycin-resistant enterococci isolates

New antimicrobials I P785 In vitro activitiy of dalbavancin against clinical vancomycin-resistant enterococci isolates B. Saager, M. Horstkotte, H. Rohde, I. Sobottka, P. Heisig (Hamburg, DE) Objectives: Dalbavancin is a lipoglycopeptide holding bactericidal antimicrobial activity against Gram-positive bacteria bringing forth noscomial infections, e.g. methicillin-resistant Staphylococcus aureus (MRSA). It is currently being filed for FDA approval for complicated skin and skin structure infections. The mechanism of action of lipoglycopeptides is similiar to other glycopeptides (e.g. teicoplanin or vancomycin) by inhibiton of cell-wall synthesis through binding to the terminal D-alanyl-D-alanine of nascent peptidoglycan chains. A collection of genotypically characterised vancomycin-resistant enterococci (VRE) was tested towards their susceptibility with a view to compare the activity of dalbavancin with recently approved and other clinical well proven antibiotics. Methods: A number of 61 strains previously described as VRE isolated at the University Medical Center Hamburg – Eppendorf (Germany) between 1995 and 2006 was chosen for susceptibility testing. MICs of dalbavancin, daptomycin, linezolid, teicoplanin, vancomycin, ampicillin, and gentamicin were determined by broth microdilution according to CLSI guidelines. Characterisation of clinically relevant glycopeptide genotypes (vanA, vanB, vanC1, vanC2/3) and species identification for enterococci were done by polymerase chain reaction. Results: A number of 57 isolates were resistant to vancomycin, while 4 four isolates showed susceptibility or intermediate susceptibility to vancomycin. MICs ranged from 4 to >256 for vancomycin and from 16 to 256 for teicoplanin. Corresponding MIC90 values were >256 and 256 for vancoymcin and teicoplanin, respectively. Determination of MICs for dalbavancin showed values ranging from
0.03 to >32 with a MIC90 of 16. The MIC90 values for daptomycin and linezolid were 4 and 2 respectively, MICs were ranging from
0.016 to 4 for daptomycin and from 1 to 16 for linezolid. Conclusion: In comparison to the well established antibiotics vancomycin and teicoplanin, dalbavancin shows improved in vitro activity against the tested isolates. With regard to the newer antimicrobial agents introducing new mechanism of actions, daptomycin and linezolid, the in vitro activity of dalbavancin was comparable. Thus, dalbavancin is a potential drug for the treatment of VRE, with its awaiting approval hopefully supplementing the arsenal of antimicrobial drugs for the treatment of nosocomial infections. P786 Susceptibility of Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis to daptomycin at a university medical centre Hamburg-Eppendorf, Germany

S197 resistant to vancomycin. MICs of daptomycin, penicillin, oxacillin, erythromycin, ciprofloxacin, gatifloxacin, moxifloxacin, sparfloxacin gentamicin, linezolid, teicoplanin, and vancomycin were determined for S. aureus and those of daptomycin, ampicillin, linezolid, teicoplanin, vancomycin and gentamicin for E. faecalis and E. faecium by broth microdilution according to CLSI guidelines. Results: All strains tested of S. aureus were susceptible to daptomycin (MICs
1 mg/mL) as well as all strains of E. faecium and E. faecalis (MICs
4 mg/mL). MICs were ranging between 0.03−1 for S. aureus and 0.25−4 and 0.5−4 for E. faecalis and E. faecium, respectively. MIC90 values were 0.5 (S. aureus), 2 (E. faecalis) and 4 (E. faecium). A total number of 25 S. aureus (11.3%) isolates with multiple resistant phenoytpe were found showing resistance to ciprofloxacin, erythromycin and oxacillin. Conclusion: Our data show that daptomycin offers good in vitro activity against S. aureus, E. faecalis and E. faecium, including isolates with multiple-resistant phenotype.

P787 Comparative in vitro activity of dalbavancin against clinical isolates of vanA, vanB, and vanC enterococci E. Cercenado, O. Cuevas, M. Marin, M.J. Goyanes, E. Bouza (Madrid, ES) Objectives: Dalbavancin (DAL) is a new lipoglycopeptide with activity against Gram-positive microorganisms. Its half-life of 8.5 days enables once-weekly dosing. In this study we compared the activity of DAL with other agents against clinical isolates of vancomycin-resistant enterococci (VRE). Methods: We tested a total of 238 well characterised non-duplicate clinical isolates of VRE recovered from patients at our institution. Origin of isolates were: wounds (69 isolates), urine (45), blood (38), peritoneal fluid (24), abscesses (17), other sterile fluids (12), intravascular catheter (12), and others (21). Multiplex PCR was used to detect vanA, vanB, vanC-1, and vanC-2 genes. The isolates were 83 E. faecalis (64 vanA, 19 vanB), 80 E. faecium (37 vanA, 43 vanB), 50 E. gallinarum (vanC1), and 25 E. casseliflavus (vanC2). Susceptibility testing was performed by the broth microdilution method in cation-adjusted Mueller-Hinton broth following CLSI guidelines. The antimicrobial agents evaluated were: dalbavancin (DAL), vancomycin (VAN), teicoplanin (TEI), and linezolid (LZD). E. faecalis ATCC 29212 and S. aureus ATCC 29213 were used as control strains. Results: The MIC50 , MIC90 , and MIC range values (mg/L) are summarised in the table.

Organisms and type (No.) Antimicrobials MIC (mg/L)

B. Saager, M. Horstkotte, H. Rohde, I. Sobottka, P. Heisig (Hamburg, DE) Objectives: Daptomycin (Cubicin® ) is the first lipopeptide bactericidal antimicrobial agent and introduces a new mechanism of action against Gram-positive bacteria. By binding to and integrating into bacterial membranes it causes a rapid depolarisation of membrane potential resulting in the inhibition of metabolism and ultimately in cell death. Being approved for the treatment of complicated skin and skin structure infections due to S. aureus, including methicillin resistant S. aureus (MRSA) and E. faecalis, daptomycin presents a promising therapeutical option for treatment of noscomial Gram-positive pathogens. To investigate the susceptibility of daptomycin facing isolates with multiple resistance phenotype in vitro, clinical isolates of S. aureus, E. faecium and E. faecalis were chosen for susceptibility testing against daptomycin and established clinically important antibiotics. Methods: 285 strains being isolated at the University Medical Center Hamburg – Eppendorf (Germany) between 2004 and 2006 were chosen for susceptibilty testing. This collective comprised 221 isolates of S. aureus including 15.4% MRSA, 41 isolates of E. faecalis and 23 isolates of E. faecium with two isolate of E. faecium being

MIC50 MIC90 Range VanA VRE (101)

VanB VRE (62)

VanC VRE (75)

Dalbavancin Vancomycin Teicoplanin Linezolid Dalbavancin Vancomycin Teicoplanin Linezolid Dalbavancin Vancomycin Teicoplanin Linezolid

8 512 64 1
0.12 32 0.5 1
0.12 8 0.25 1

64 1,024 128 2 1 512 0.5 2
0.12 16 0.5 2


0.12−64 256–1,024 32–128 1−2
0.12−2 16–1,024
0.12−1 1−2
0.12−0.5 4−16
0.12−0.5 1−2

Conclusions: Dalbavancin was more active than comparator glycopeptides and presented good activity against vanB, and vanC enterococci, however, it was inactive against vanA enterococci.