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Using Mathematical Models to Optimize Topical Fluoroquinolone Regimens for Preoperative Prophylaxis in Ophthalmic MRSA Infections
Location: East Ballroom
Mentor: Dr. Xi Huo
Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of ocular infections and poses a high risk for postoperative complications in patients undergoing intraocular procedures. Conventional fluoroquinolone monotherapy often leads to rapid bacterial adaptation and resistance, necessitating alternative prophylactic strategies. We propose a novel rotational fluoroquinolone regimen that exploits collateral sensitivity to prevent resistance development in ocular MRSA infections. Both moxifloxacin and ciprofloxacin primarily inhibit topoisomerase IV in Gram-positive bacteria; however, moxifloxacin’s bulky 8-methoxy and C-7 bicyclic side chain confers high binding affinity to the wild-type enzyme, while also selecting for resistance mutations that alter its binding pocket. These mutations reduce moxifloxacin efficacy but simultaneously enhance the binding of ciprofloxacin, which possesses a less sterically hindered structure. Our mathematical modeling and experimental data suggest that initiating treatment with moxifloxacin induces selective pressure leading to resistance mutations, which in turn increase MRSA’s collateral sensitivity to subsequent ciprofloxacin exposure. Rotating between these agents disrupts the stepwise accumulation of resistance, resulting in enhanced bacterial suppression. Furthermore, frequent dosing minimizes the risk of bacterial regrowth and reduces drug-specific toxicity associated with prolonged monotherapy. Our model integrates time-dependent and concentration-dependent killing kinetics, confirming that dynamic alternation between fluoroquinolones significantly improves MRSA eradication in ocular tissues. These findings provide a theoretical framework for implementing rotational fluoroquinolone therapy as an optimized preoperative prophylactic strategy
against ocular MRSA infections, warranting further clinical investigation.
