Activity of Telavancin against Staphylococcus aureus Isolates, Including Those with Decreased Susceptibility to Ceftaroline, from Cystic Fibrosis Patients.

Methicillin-resistant (MRSA) acquisition in cystic fibrosis (CF) patients confers a clinical outcome worse than that in non-CF patients with an increased rate of declined lung function. Telavancin, an approved lipoglycopeptide used to treat infections due to , has a dual mode of action causing inhibition of peptidoglycan synthesis and membrane depolarization. MRSA infections in CF patients remain an important problem with no foreseeable decline in prevalence rates. Although telavancin is currently in clinical use for the treatment of complicated skin infections and hospital-acquired pneumonia, the activity against infections in CF patients has not been investigated. In this work, we studied the activity of telavancin against CF patient-derived strains collected from geographically diverse CF centers in the United States. We found that the telavancin MIC was 0.06 μg/ml, 8-fold lower than the ceftaroline or daptomycin MIC and 25-fold lower than the linezolid and vancomycin MIC We demonstrate that telavancin at serum free concentrations has rapid bactericidal activity, with a decrease of more than 3 log CFU/ml being achieved during the first 4 to 6 h of treatment, performing better in this assay than vancomycin and ceftaroline, including against strains resistant to ceftaroline. Telavancin resistance was infrequent (0.3%), although we found that it can occur in both CF- and non-CF patient-derived strains by progressive passages with subinhibitory concentrations. Genetic analysis of telavancin-resistant mutants showed gene polymorphisms in cell wall and virulence genes and increased survival in a infection model. Thus, we conclude that telavancin represents a promising therapeutic option for infections in CF patients with potent activity and a low resistance development potential.