Intracellular and antibiofilm activity of delafloxacin against staphylococci.
Background and Objectives. 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.  Methods. The antibiofilm activity of delafloxacin was assessed using 2 pairs of levofloxacin-susceptible/resistant Staphylococcus aureus strains (6850-S/6850-R; Clin-S/Clin-R), as well as ten clinical strains from BJI (S. aureus, n=5; S. epidermidis, n=5). The 90% minimal biofilm eradication concentration (MBEC90) of delafloxacin was compared with that of rifampicin, vancomycin, and levofloxacin after a 24-hour 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. Results. Delafloxacin showed significant activity against levofloxacin-susceptible staphylococci in planktonic (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 Clin-S), but a strain-dependent activity against levofloxacin-resistant staphylococci (MIC [0.032-8] mg/L), both in biofilm (MBEC90: [0.064->4] mg/L) and in the intracellular compartment (bacterial eradication at bone concentration: -63.6% for 6850-R and null for Clin-R). Conclusions. This study confirms the promising potential of delafloxacin to treat staphylococcal BJIs, but further investigations, including animal models and clinical trials, are needed to better understand its efficacy, particularly its variable effect against levofloxacin-resistant strains.