title: Update of the activity of telavancin against a global collection of Staphylococcus aureus causing bacteremia, including endocarditis (2011-2014).
abstract: The efficacy and safety of telavancin is under evaluation for the treatment of subjects with complicated Staphylococcus aureus bacteremia and S. aureus right-sided infective endocarditis. This study evaluated the telavancin activity against a global collection of S. aureus causing bloodstream infections (BSI), including endocarditis, to support the development of bacteremia/endocarditis clinical indications. This study included a total of 4191 S. aureus [1490 methicillin-resistant S. aureus (MRSA)], which were unique (one per patient) clinical isolates recovered from blood samples collected during 2011-2014 in a global network of hospitals. All isolates were deemed responsible for BSI, including endocarditis, by local guidelines. Isolates were tested for susceptibility by broth microdilution. Telavancin (MIC50/90, 0.03/0.06 μg/ml) inhibited all S. aureus at ≤0.12 μg/ml, the breakpoint for susceptibility. Equivalent minimum inhibitory concentration (MIC) values (MIC50/90, 0.03/0.06 μg/ml) were obtained for telavancin against methicillin-susceptible S. aureus (MSSA) and MRSA isolates, as well as MRSA from community and healthcare origins. Similar telavancin activities (MIC50, 0.03 μg/ml) were observed against MRSA subsets from North America and Europe, while isolates from the Asia-Pacific (APAC) and Latin America regions had MIC50values of 0.06 μg/ml. MRSA with vancomycin MIC values of 2-4 μg/ml and the multidrug resistance (MDR) subset had telavancin MIC50results of 0.06 μg/ml, although the MIC100result obtained against these subsets remained identical to those of MSSA (MIC100, 0.12 μg/ml, respectively). This study updates the telavancin in vitro activity, which continues to demonstrate great potency against invasive S. aureus, regardless of the susceptibility phenotype or demographic characteristics (100.0% susceptible), and supports the sought-after subsequent indications.
authors.affiliation: JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA, 52317, USA. rodrigo-mendes@jmilabs.com.
authors.forename: R E
authors.initials: RE
authors.lastname: Mendes
authors.affiliation: JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA, 52317, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Sader
authors.affiliation: Theravance Biopharma US, Inc., South San Francisco, CA, USA.
authors.forename: J I
authors.initials: JI
authors.lastname: Smart
authors.affiliation: JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA, 52317, USA.
authors.forename: M
authors.initials: M
authors.lastname: Castanheira
authors.affiliation: JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA, 52317, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Flamm
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000382:microbiology*; D004697:Endocarditis, Bacterial / Q000382:microbiology*; D014943:Global Health; D006801:Humans; D000077427:Lipoglycopeptides; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077427:Lipoglycopeptides; C487637:telavancin