IN VITRO DALBAVANCIN ACTIVITY AGAINST CLINICAL ISOLATES OF STAPHYLOCOCCUS SPP. AND SUBSEQUENT INTERACTION WITH HUMAN PHAGOCYTES

Introduction: Dalbavancin is a semisynthetic long-acting lipoglycopeptide antibiotic recently approved in the United States by the Federal Drug Administration (FDA) for treatment of adult patients with acute bacterial skin and skin structure infections caused by susceptible Gram-positive bacteria. Among the Gram-positive bacteria, dalbavancin has a broad spectrum of action against most microorganisms, including those resistant to other antimicrobial families. The aims of this study were to evaluate the activity of dalbavancin against Staphylococcus aureus and Staphylococcus epidermidis clinical strains and to determine the straightforward performance of dalbavancin upon the binomial antibiotic resistant/susceptible bacterium and host defenses, to establish its potential immunomodulating activity. Materials and Methods: Twenty-five isolates of methicillin-susceptible S. aureus (MSSA), 25 isolates of methicillin-resistant S. aureus (MRSA), 25 isolates of methicillin-resistant and teicoplanin susceptible S. epidermidis (MRSE-TeicoS), 25 isolates of methicillin-resistant and teicoplanin resistant S. epidermidis (MRSE-Teico R) were collected from various clinical sources and studied. Minimum inhibitory concentrations (MICs) of dalbavancin were determined by broth microdilution according to Clinical and Laboratory Standards Institute guidelines. Additionally the human polymorphonuclear cells (PMNs) functional activity [(microbicidal activity and cytokine release profile (TNF-α, IL-1β, IL-10)] was investigated by incubating MRSA and phagocytes for 30, 60, 90 and 120 minutes with dalbavancin at MIC level. Results: Dalbavancin demonstrated in vitro activity against all isolates tested with MICs ≤ 0.12 μg/ mL, the FDA susceptible breakpoint for S. aureus. The normal MIC distribution among S. aureus (both MSSA and MRSA) and S. epidermidis (both MRSE-Teico S and MRSE-Teico R) isolates was between 0.03-0.12 μg/mL, with a clear modal MIC of 0.06 μg/mL for MSSA, MRSA and MRSE-Teico S, and 0.12 μg/mL for MRSE-Teico R. Moreover, the data on PMN activity showed that dalbavancin at MIC concentration had effect on both MRSA intracellular killing and cytokine release, in comparison with dalbavancin-free controls, for the entire period of observation. Conclusions: The need for new agents with potent activity against staphylococci is acute due to increased resistance to most common currently available antibiotics. Our results confirm and extent previous literature data on the antistaphylococcal activity of dalbavancin: it has activity not only in fighting staphylococcal resistant strains, but also in influencing PMN microbicidal activity. These data support the continued clinical study of dalbavancin in infections where staphylococci are prevalent.