Molecular determinants for Ceftaroline resistance in Clinical Isolates of Methicillin-Resistant Staphylococcus Aureus: A Cross sectional Pilot Study

Methicillin-resistant Staphylococcus aureus (MRSA) infection poses a significant public health challenge. Despite efforts to control its spread, MRSA continues to cause a substantial burden of morbidity and mortality worldwide. The emergence of community-acquired MRSA strains further complicates the issue. β-lactam antibiotics have historically been frontline treatments for staphylococcal infections. However, the rise of β-lactam resistance in MRSA strains renders these antibiotics ineffective, limiting treatment options and increasing the risk of treatment failure, persistent infections, and adverse patient outcomes. Thus, healthcare providers are compelled to turn to second-line agents, such as vancomycin, daptomycin, or linezolid. However, these alternatives may be associated with drawbacks such as reduced potency due to slow rate of bactericidal activity, bacteriostatic effect or poor tissue penetration, higher rates of adverse effects and increased risk of developing resistance over time. Ceftaroline is a fifth-generation cephalosporin is a promising treatment option for MRSA infections due to its unique mechanism of action and broad spectrum of activity.  

Next generation sequencing is a powerful tool to compare the whole genomes and analyze the single base pair variations and polymorphisms (SNPs) found within the antibiotic resistant genes. Previous literature shows an antimicrobial susceptibility rate of 95% for Ceftaroline among the clinical MRSA isolates. Literature is however, limited especially in Indian scenario. Accounting for possible emergence of antimicrobial Ceftaroline resistance among MRSA isolates, we aim to conduct a pilot study as a part of future comprehensive trial that may identify the possible molecular determinants (known and unknown) contributing to Ceftaroline resistance in MRSA isolates identified within clinical samples obtained from admitted patients in our tertiary care hospital.