| Abstract
| - Objectives. Staphylococcus aureus survives inside eukaryotic cells. Our objective was to assess the activity of NZ2114, a novel peptidic antibiotic, against intracellular S. aureus in comparison with established antistaphylococcal agents acting on the bacterial envelope with a distinct mechanism. Methods. The extracellular (broth) and intracellular (THP-1 monocytes) activities of NZ2114 were compared with those of vancomycin and daptomycin against methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA). Results. All three compounds showed an extracellular bactericidal effect (>3 log10 kill) against MSSA and MRSA. Daptomycin and NZ2114 also exhibited bactericidal activity against VRSA. The extracellular killing was concentration dependent for all three compounds within the range of drug concentrations tested. The intracellular experiments demonstrated a maximal intracellular effect of NZ2114 after 24 h as a 5 log10 cfu reduction against MSSA (ATCC 25923), while the activity was a 0.9 log10 cfu reduction against MRSA and a 0.2 log10 cfu reduction against VRSA. For comparison, the intracellular activity of daptomycin was a 1.0 log10 cfu reduction against MSSA, a 0.8 log10 cfu reduction against MRSA and a 0.3 log10 cfu reduction against VRSA. Vancomycin showed activity against both MSSA and MRSA (0.6 log10 cfu reduction), whereas VRSA was resistant to vancomycin. Conclusions. NZ2114 displayed similar extracellular and intracellular activities as daptomycin, and was more effective than vancomycin against the intracellular forms of susceptible bacteria. However, the study also showed that the intracellular activities of NZ2114 and daptomycin are weaker than their extracellular activities.
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