In vivo pharmacodynamic study of contezolid acefosamil, a prodrug of contezolid for oral and intravenous administration.

OBJECTIVES: Contezolid acefosamil is a novel O-acyl phosphoramidate prodrug of contezolid. In the current study, we aimed to systemically evaluate the efficacy of contezolid acefosamil against infections caused by multiple Gram-positive pathogens, and compare the efficacy of the prodrug by oral and intravenous administrations. METHODS: The in vivo pharmacodynamic efficacy of contezolid acefosamil was evaluated in mouse models of systemic (with five S. aureus, three S. pneumoniae and two S. pyogenes bacterial isolates) and thigh (with two S. aureus isolates) infections using linezolid as the reference agent. RESULTS: In both models, contezolid acefosamil administrated either orally or intravenously, demonstrated high antibacterial efficacy similar to linezolid, and the antibacterial efficacy of oral and intravenous contezolid acefosamil were comparable. CONCLUSIONS: The high aqueous solubility and great efficacy of contezolid acefosamil support its clinical development as an injectable and oral antibiotic suitable for serious Gram-positive infections.

[Progress on femorotibial mechanical axis of total knee arthroplasty].

Femorotibial mechanical axis (FTMA) is one of important factors influencing clinical effect after total knee arthroplasty (TKA). It is generally believed that the range of lower limb alignment after TKA is controlled within neutral FTMA ± 3 °, which has more advantages in improving joint function, prolonging prosthesis survival rate and reducing revision rate, and obtain better clinical results. Therefore, neutral FTMA is also considered to be the gold standard for TKA. However, with the application of computer-assisted surgery and other technologies, the alignment of FTMA is more accurate than before, but the clinical effect after surgery has not significantly improved. Some scholars have begun to question the necessity of neutral alignment of FTMA, and proposed alignment methods such as kinematics and retained residual deformity, which could achieve better clinical effects. In recent years, it has been reported that FTMA might not be the most important factor influencing postoperative clinical effects, and it is suggested that the arrangement and measurement of lower limbs and the effects on adjacent joint functions could affect clinical effect after TKA. The paper reviews neutral FTMA alignment is still an important factor for success of TKA. After a thorough evaluation according to the patient's condition, it should be appropriately applied in the case of neutral FTMA alignment; the operator should explore other factors which affect clinical outcome after TKA, and improve it to achieve the best therapeutic effect.