Design, Synthesis and Biological Evaluation of Sulfenimine Cephalosporin Analogues as β-Lactamase Inhibitors

A series of sulfenimine cephalosporin derivatives（6a--6t） was designed, synthesized and evaluated for their inhibitory activity against class A β-lactamase（TEM-1） derived from E. coli, and class C β-lactamase （cephalosporinase） derived from wild Bacillus subtilis in cell-free systems. Most of the tested compounds showed enhanced inhibitory activity against class C β-lactamase（cephalosporinase） compared with tazobactam. The most promising compounds 6c and 6o in combination with cefradine（IC50=1.80 and 1.59 gmol/L, respectively） were fur- ther investigated against a series of clinical isolated β-lactamase-producing bacterial strains. The results reveal that compounds 6c and 60 in combination with cefradine show two to four times more activity than cefradine alone against methicillin-sensitive Staphylococcus aureus（MSSA） and Klebsiella pneumoniae. The data suggest that the sulfenimine moiety may be beneficial to the activity and selectivity of inhibitors.

红曲米致横纹肌溶解症2例

2例患者(例1男,61岁;例2女,58岁)均因血脂异常使用红曲米6 g口服、1次/d。例1有血吸虫性肝硬化、胆汁淤积性肝炎,三酰甘油5.32 mmol/L,口服红曲米26 d后出现四肢无力、肌酸激酶(CK)604 U/L。立即停用红曲米,3 d后患者出现下肢肌肉酸痛,CK最高达117748 U/L,经地塞米松、补液水化治疗12 d后上述症状逐渐消失,CK 79 U/L。例2为急性肝炎患者,三酰甘油2.34 mmol/L,口服红曲米24 d后出现双下肢乏力、肌肉酸痛,CK最高达52222 U/L。立即停用红曲米,予甲泼尼龙、补液水化等治疗12 d后病情好转,CK 210 U/L。