Test results: characterising the antimicrobial activity of daptomycin

ABSTRACT Daptomycin is the first in a new class of antibiotics, the cyclic lipopeptides. This review discusses the extensive in vitro tests performed to characterise the antimicrobial activity of daptomycin. These tests have established daptomycin's activity against most Gram-positive bacteria, including methicillin-sensitive and -resistant Staphylococcus aureus , vancomycin-resistant enterococci and multidrug-resistant coagulase-negative staphylococci. Daptomycin possesses rapid, concentration-dependent bactericidal activity against Gram-positive organisms. Interestingly, this in vitro bactericidal activity is maintained at high inoculum densities and against bacteria in the stationary phase of growth. In addition, in vitro tests have demonstrated a prolonged, concentration-dependent post-antibiotic effect against Gram-positive bacteria. The level of protein binding of daptomycin is high. However, daptomycin binds only weakly to albumin, and is two- to four-fold more active than would be predicted from its free drug concentration. In vitro studies have shown low spontaneous resistance rates of −10 for S. aureus and −9 for Staphylococcus epidermidis , Enterococcus faecalis and Enterococcus faecium . In summary, in vitro testing clearly demonstrates that daptomycin is an exciting new option for the treatment of Gram-positive infections.