Higurashi Y, Okuzumi K, Yoneyama A, Nakahara K
Department of clinical laboratories, Tokyo University Hospital.
Jpn J Antibiot. 1997 Dec;50(12):907-16.
The in vitro antibacterial activity of cefozopran (CZOP) against recent clinical isolates was evaluated and compared with those of ceftazidime (CAZ), cefpirome (CPR), cefepime (CFPM), cefotaxime (CTX), sulbactam/cefoperazone (S/C), imipenem (IPM), oxacillin (MPIPC), and flomoxef (FMOX). MIC80 values of CZOP for methicillin-susceptible Staphylococcus aureus (MSSA, n = 41), methicillin-resistant Staphylococcus aureus (MRSA, n = 57), Streptococcus pneumoniae (n = 45), Enterococus faecalis (n = 49), Enterobacter cloacae (n = 50), Citrobacter freundii (n = 45), Serratia marcescens (n = 45), and Pseudomonas aeruginosa (n = 100) were 1, 32, 2, 16, 4, 1, 0.25, 8 micrograms/ml, respectively. CZOP was more active than CPR against P. aeruginosa and exhibited similar activity to CPR against other species. CZOP was especially active against S. marcescens with MIC values lower than 1 microgram/ml against all strains tested. CZOP was similarly active to or more active than CFPM against all species except for C. freundii. CZOP was not active against MRSA. Thus, we investigated the in vitro combination effects of CZOP/vancomycin (VCM) and CZOP/arbekacin (ABK) using the checkerboard method. The interaction between CZOP and VCM ranged from additive activity (0.5 < FIC index < or = 1.00, n = 37) to synergistic activity (FIC index < 0.50, n = 1), except for one strain showing indifference (1.00 < FIC index < or = 2.00). The interaction between CZOP and ABK ranged from additive activity (n = 22) to synergistic activity (n = 1). These date suggest the potential effect of combination therapy of (CZOP) and VCM or ABK against MRSA. The combined therapy is suggested to be useful to reduce side effects in patients with impared renal function, to reduce the administration dose of VCM or to treat infections of sites where achievable drug concentrations are lower than those commonly achieved in the bloodstream. We also investigated the combination effects of CZOP/AMK and CZOP/GM against CZOP-resistant P. aeruginosa (MIC > 16 micrograms/ml). The combination of CZOP/AMK showed additive activity (n = 9) to synergistic activity (n = 2). The combination of CZOP/GM showed additive activity (n = 5). These results suggest that combinations of CZOP with AMK or GM are effective in treating P. aeruginosa.
评估了头孢唑兰（CZOP）对近期临床分离菌株的体外抗菌活性，并与头孢他啶（CAZ）、头孢匹罗（CPR）、头孢吡肟（CFPM）、头孢噻肟（CTX）、舒巴坦/头孢哌酮（S/C）、亚胺培南（IPM）、苯唑西林（MPIPC）和氟氧头孢（FMOX）进行了比较。CZOP对甲氧西林敏感金黄色葡萄球菌（MSSA，n = 41）、甲氧西林耐药金黄色葡萄球菌（MRSA，n = 57）、肺炎链球菌（n = 45）、粪肠球菌（n = 49）、阴沟肠杆菌（n = 50）、弗氏柠檬酸杆菌（n = 45）、粘质沙雷氏菌（n = 45）和铜绿假单胞菌（n = 100）的MIC80值分别为1、32、2、16、4、1、0.25、8微克/毫升。CZOP对铜绿假单胞菌的活性比CPR高，对其他菌种表现出与CPR相似的活性。CZOP对粘质沙雷氏菌特别活跃，对所有测试菌株的MIC值均低于1微克/毫升。除弗氏柠檬酸杆菌外，CZOP对所有菌种的活性与CFPM相似或更高。CZOP对MRSA无活性。因此，我们采用棋盘法研究了CZOP/万古霉素（VCM）和CZOP/阿贝卡星（ABK）的体外联合效应。除1株表现为无作用（1.00 < FIC指数≤2.00）外，CZOP与VCM之间的相互作用范围从相加活性（0.5 < FIC指数≤1.00，n = 37）到协同活性（FIC指数< 0.50，n = 1）。CZOP与ABK之间的相互作用范围从相加活性（n = 22）到协同活性（n = 1）。这些数据表明（CZOP）与VCM或ABK联合治疗对MRSA有潜在效果。联合治疗被认为有助于降低肾功能受损患者的副作用，减少VCM的给药剂量或治疗药物可达到的浓度低于血液中通常达到浓度的部位的感染。我们还研究了CZOP/阿米卡星（AMK）和CZOP/庆大霉素（GM）对耐CZOP铜绿假单胞菌（MIC > 16微克/毫升）的联合效应。CZOP/AMK的联合显示出从相加活性（n = 9）到协同活性（n = 2）。CZOP/GM的联合显示出相加活性（n = 5）。这些结果表明CZOP与AMK或GM联合可有效治疗铜绿假单胞菌。
