Assessment of Minimum Inhibitory Concentrations of Telavancin by Revised Broth Microdilution Method in Phase 3 Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia Clinical Isolates

摘要

IntroductionThe 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.MethodsIsolates from patients who participated in the phase 3 Assessment of Telavancin for Treatment of HAP Studies were retested using the rBMD method.ResultsRetesting of 647 isolates produced a range of telavancin MIC values from 0.015?μg/mL to 0.12?μg/mL with MICsub50/90/sub values of 0.06/0.06?μg/mL for the total pool of samples. For methicillin-resistant S. aureus (MRSA), MICsub50/90/sub values were 0.06/0.12?μg/mL. These values are up to 4-fold lower than MICsub50/90/sub values 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).ConclusionResults from the rBMD method support the in vitro potency of telavancin against S. aureus .Trial registrationATTAIN (NCT00107952 and NCT00124020).FundingTheravance Biopharma Antibiotics, Inc.