Differences in Pharmacokinetic/Pharmacodynamic Parameters of Tedizolid Against VRE and MRSA

Purpose Vancomycin-resistant enterococci (VRE) have recently become a major cause of nosocomial infections and a global public health concern. Tedizolid exhibits powerful antibacterial activity against VRE in vitro , but its pharmacokinetic/pharmacodynamic (PK/PD) parameters remain unclear. Therefore, we aimed to determine the PK/PD indices of tedizolid action on VRE and the mechanisms underlying the PK/PD indices differences of tedizolid against VRE and methicillin-resistant Staphylococcus aureus (MRSA). Methods Optimal PK/PD target values of tedizolid were determined in vitro , based on time-kill curves and post-antibiotic effects (PAEs), and in vivo , using mouse models of thigh infection with VRE and MRSA strains. Results The tedizolid bactericidal activity on VRE and MRSA was time-dependent. Correlations were closest between f AUC 24 /MIC and the tedizolid PK/PD index against MRSA and VRE. To achieve 1 log 10 kill tedizolid f AUC 24 /MIC in neutropenic mouse models of thigh infection with VRE and MRSA should be 14.2 and 138.5, respectively. The PAEs of tedizolid against VRE and MRSA were 2.39 and 0.99 h, respectively. Conclusion Tedizolid showed bactericidal effects against VRE even in neutropenic mice unlike MRSA, which could be attributed to its longer PAE against VRE. Hence, we hypothesize that tedizolid treatment against VRE infections is promising for achieving therapeutic success in clinical.