# In vitro antibiofilm and intracellular activity of delafloxacin against Staphylococcus aureus and Staphylococcus epidermidis in bone and joint infections

## TL;DR

Delafloxacin shows strong in vitro antibiofilm and intracellular activity against some staphylococcal bone and joint infection strains, but its effectiveness varies against resistant strains.

## Contribution

This study is the first to evaluate delafloxacin's antibiofilm and intracellular activity in a bone context against both levofloxacin-susceptible and resistant staphylococcal strains.

## Key findings

- Delafloxacin effectively targets levofloxacin-susceptible staphylococci in biofilm and intracellular environments.
- Activity against levofloxacin-resistant strains is strain-dependent and less consistent.
- Delafloxacin shows promise for treating staphylococcal bone and joint infections but requires further clinical validation.

## 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 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). 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.

Staphylococcal bone and joint infections (BJIs) represent significant challenges for treatment. Fluoroquinolones, especially levofloxacin, play a key role in their management; however, resistance to levofloxacin is common among methicillin-resistant strains. Delafloxacin, a novel broad-spectrum fluoroquinolone, may represent a therapeutic alternative, but very limited data are available regarding its clinical utility in BJIs. In this context, our study aimed to investigate the in vitro antibiofilm and intracellular activities of delafloxacin in a bone context, using both levofloxacin-susceptible and levofloxacin-resistant staphylococcal strains (Staphylococcus aureus and Staphylococcus epidermidis). Our results demonstrate a significant activity of delafloxacin against levofloxacin-susceptible staphylococci both in biofilm and within osteoblasts. However, its efficacy against levofloxacin-resistant strains was variable and appeared to be strain-dependent, both in biofilm and intracellular conditions. 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.