Preclinical and clinical evaluation of vancomycin plus delpazolid combination therapy for MRSA bacteremia: a multicenter, double-blinded, randomized, parallel design, phase IIa clinical trial

Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) bacteremia presents a serious clinical challenge due to limited treatments and high mortality. This study evaluated the potential role of delpazolid, an oral oxazolidinone, in combination with vancomycin for MRSA bacteremia. Preclinical studies demonstrated delpazolid's antimicrobial activity comparable to vancomycin and daptomycin, and in the <i>Galleria mellonella</i> infection model, combination therapy significantly improved survival rates over monotherapy. The early-terminated Phase IIa clinical study showed that the combination regimen had an acceptable safety profile, with no apparent increase in adverse events compared to vancomycin monotherapy. While overall cure rates and bacteremia clearance were numerically higher in the combination group, these differences were not statistically significant. These preliminary findings underscore the need for larger, adequately powered clinical trials to clarify the clinical role of delpazolid combination therapy in MRSA infections.