Intracellular activity of the peptide antibiotic NZ2114: studies with Staphylococcus aureus and human THP-1 monocytes, and comparison with daptomycin and vancomycin.

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 log(10) 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 log(10) cfu reduction against MSSA (ATCC 25923), while the activity was a 0.9 log(10) cfu reduction against MRSA and a 0.2 log(10) cfu reduction against VRSA. For comparison, the intracellular activity of daptomycin was a 1.0 log(10) cfu reduction against MSSA, a 0.8 log(10) cfu reduction against MRSA and a 0.3 log(10) cfu reduction against VRSA. Vancomycin showed activity against both MSSA and MRSA (0.6 log(10) 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.