Genetic Sequencing and Evaluation of Delafloxacin Susceptibility in Community-Acquired Mrsa Causing Skin, Soft Tissue, and Musculoskeletal Infections

Indiscriminate use of quinolones, especially after the COVID-19 pandemic, has contributed to increased bacterial resistance, including methicillin-resistant Staphylococcus aureus (MRSA). Fluoroquinolones are widely used in clinical practice for treatment of skin, soft tissue, and musculoskeletal infections (SST-MSI). Delafloxacin, a new fluoroquinolone, was approved in Brazil in 2022 for the treatment of SST-MSI. This study aimed to evaluate the delafloxacin susceptibility profile of MRSA isolates causing community-acquired SST-MSI. Thirty-five MRSA isolates obtained from biopsies of skin, soft tissue, bone, or synovial fluid were evaluated. Minimum inhibitory concentration (MIC) for delafloxacin was determined by E-test® according to BRCAST breakpoints. Isolates underwent whole-genome sequencing using the Illumina® platform. Of the 35 MRSA isolates, 71.4% (n=25) were susceptible and 28.6% (n=10) resistant to delafloxacin. Among resistant isolates, 70% (n=7) had MIC >0.5 μg/mL, with a maximum value of 2 μg/mL. In 90% of resistant isolates, mutations were found in quinolone resistance-determining regions, most commonly S84L in gyrA and S80Y in parC/grlA. One isolate with MIC 0.38 μg/mL had no known mutations or efflux pump genes. 37.1% (n=13) of isolates were resistant to ciprofloxacin. MRSA isolates causing community-acquired SST-MSI showed a high rate of susceptibility to delafloxacin. However, mutations associated with quinolone resistance were identified in part of the isolates, underscoring the need for further studies to elucidate delafloxacin resistance mechanisms and guide its rational use in SST-MSI.