title: Assessment of Minimum Inhibitory Concentrations of Telavancin by Revised Broth Microdilution Method in Phase 3 Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia Clinical Isolates.
abstract: BACKGROUND
  The broth microdilution method (BMD) for testing telavancin minimum inhibitory concentrations (MICs) was revised (rBMD) in 2014 to improve the accuracy, precision, and reproducibility of the testing method. The aim of this study was to determine the effect of the revised method on telavancin MIC values for Staphylococcus aureus (S. aureus) clinical isolates obtained from hospital-acquired pneumonia (HAP) patients.
  
  
  METHODS
  Isolates from patients who participated in the phase 3 Assessment of Telavancin for Treatment of HAP Studies were retested using the rBMD method.
  
  
  RESULTS
  Retesting of 647 isolates produced a range of telavancin MIC values from 0.015 µg/mL to 0.12 µg/mL with MIC50/90values of 0.06/0.06 µg/mL for the total pool of samples. For methicillin-resistant S. aureus (MRSA), MIC50/90values were 0.06/0.12 µg/mL. These values are up to 4-fold lower than MIC50/90values obtained using the original method. These results were used in part to justify lowering the telavancin breakpoints. All tested isolates remained susceptible to telavancin at the revised susceptibility breakpoint of ≤0.12 µg/mL. Overall, the clinical cure rate for microbiologically evaluable telavancin-treated patients was 78% for S. aureus, 76% for patients with MRSA, and 79% for patients with isolates with reduced susceptibility to vancomycin (MIC ≥1 µg/mL).
  
  
  CONCLUSIONS
  Results from the rBMD method support the in vitro potency of telavancin against S. aureus.
  
  
  BACKGROUND
  ATTAIN (NCT00107952 and NCT00124020).
  
  
  BACKGROUND
  Theravance Biopharma Antibiotics, Inc.
authors.affiliation: Theravance Biopharma US, Inc., South San Francisco, CA, USA. jsmart@smartmicrobiology.com.
authors.forename: Jennifer I
authors.initials: JI
authors.lastname: Smart
authors.affiliation: Duke University, Durham, NC, USA.
authors.forename: Gordon Ralph
authors.initials: GR
authors.lastname: Corey
authors.affiliation: Department of Internal Medicine and Division of Infectious Diseases, CEMIC, Buenos Aires, Argentina.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Stryjewski
authors.affiliation: Theravance Biopharma US, Inc., South San Francisco, CA, USA.
authors.forename: Whedy
authors.initials: W
authors.lastname: Wang
authors.affiliation: Theravance Biopharma US, Inc., South San Francisco, CA, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Barriere
keywords: Hospital-acquired pneumonia; Lipoglycopeptide; Staphylococcus aureus; Telavancin; Ventilator-associated pneumonia