In vitro antibiofilm and intracellular activity of delafloxacin against Staphylococcus aureus and Staphylococcus epidermidis in bone and joint infections
Abstract
ABSTRACT Staphylococcal bone and joint infections (BJIs) represent significant challenges for treatment. Fluoroquinolone-based combination therapies, especially involving levofloxacin, are pivotal antimicrobials in their management. However, resistance to levofloxacin is prevalent in methicillin-resistant strains. Delafloxacin, a novel broad-spectrum fluoroquinolone, may offer a therapeutic alternative. This study aimed to investigate the in vitro antibiofilm and intracellular activities of delafloxacin in a bone context. The antibiofilm activity of delafloxacin was assessed using two pairs of levofloxacin-susceptible/resistant Staphylococcus aureus strains (6850-S/6850-R; Clin-S/Clin-R), as well as 10 clinical strains from BJI ( S. aureus , n = 5; Staphylococcus epidermidis , n = 5). The 90% minimal biofilm eradication concentration (MBEC90) of delafloxacin was compared with that of rifampicin, vancomycin, and levofloxacin after a 24-h treatment of biofilm-embedded staphylococci. Additionally, the intracellular activity of delafloxacin and comparators was evaluated using the 6850-S/6850-R and Clin-S/Clin-R strains in an intraosteoblastic (MG-63) infection model. Delafloxacin showed significant activity against levofloxacin-susceptible staphylococci in planktonic (minimum inhibitory concentration [MIC]: [0.008–0.016] mg/L) and biofilm states (MBEC90: [0.008–0.064] mg/L), and inside osteoblasts (bacterial eradication at bone concentration: −75.0% for 6850-S and −34.8% for…
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