不同配比头孢噻肟与舒巴坦的体外抗菌活性

目的研究不同配比的头孢噻肟/舒巴坦及头孢噻肟单剂对临床分离菌体外抗菌作用。方法测定644株细菌的最低抑菌浓度(MIC)、最低杀菌浓度(MBC),观察细菌接种量、培养基酸碱度和血清蛋白含量对体外药效学的影响。结果头孢噻肟/舒巴坦(1∶1,2∶1)对革兰阳性球菌MIC50为0.06~32mg·L-1;对革兰阴性杆菌MIC90为0.25~32mg·L-1,是头孢噻肟单剂的1/4~1/8。结论1∶1,2∶1配比的头孢噻肟/舒巴坦对绝大多数临床感染细菌有很强的抗菌活性,明显优于头孢噻肟单剂和头孢噻肟/舒巴坦其他配比。     

头孢噻肟与他唑巴坦不同配比体外抗菌作用研究

目的研究4种不同配比的头孢噻肟/他唑巴坦(1:1、3:1、5:1、7:1)及头孢噻肟单剂对临床分离致病菌的体外抗菌作用。评价头孢噻肟联合他唑巴坦复方制荆的抗菌活性及不同配比间的差异。方法对临床分离的致病菌(β-内酰胺酶阳性)665株作药物敏感试验。采用琼脂平板二倍稀释法测定最低抑菌浓度(MIC)、试管二倍稀释法测定最低杀菌浓度(MBC)。结果不同配比的头孢噻肟与他唑巴坦均有强大的杀菌作用,明显优于头孢噻肟单剂。对临床分离的大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌、宋内氏志贺菌、福氏志贺菌、伤寒沙门菌的MIC90为0.25-16mg/L,比头孢噻肟的活性提高1-32倍。4种不同配比的头孢噻肟/他唑巴坦对(艹卓)革兰阳性菌抗菌活性无明显差异,其中对金黄色葡萄球菌、表皮葡萄球菌和溶血葡萄球菌的MIC50为0.125-16mg/L,活性较头孢噻肟高1-32倍,MIC90为1-32mg/L,活性较头孢噻肟高2-8倍。结论5:1配比的头孢噻肟/他唑巴坦复方制剂对大多数临床分离致病菌具有较强的体外抗菌作用,降低产酶菌耐药性,作用与1:1和3:1配比相当。     

不同配比头孢噻肟与他唑巴坦体外抗菌作用

目的 研究不同配比的头孢噻肟／他唑巴坦外抗菌作用。方法 测定568 株临床分离菌的最低抑菌浓度(MIC)和最低杀菌浓度(MBC)。观察细菌接种 量、培养基pH和血清蛋白含量对体外抗菌活性的影响。结果 不同配比头孢 噻肟与他唑巴坦的抗菌活性无明显差异。与头孢噻肟单剂相比,对革兰阴性菌 的MIC90为0．25-16 mg·L-1,活性提高1-32倍,对葡萄球菌MIC50为0．12- 16 mg·L-1,活性提高1-32倍,MIC90为1-32 mg·L-1,活性提高2-8倍。结 论 头孢噻肟与他唑巴坦复方制剂体外抗菌作用远高于单剂头孢噻肟。3种 (1:1,3:1,5:1)配比抑酶抗菌作用相当。     

不同配比的头孢曲松钠/舒巴坦钠体外抗菌活性比较

目的:比较不同配比的头孢曲松钠/舒巴坦钠(CRO/SBT)及头孢曲松钠(CRO)单剂对黑龙江地区临床分离致病菌的体外抗菌活性.方法:采用琼脂二倍稀释法测定不同配比CRO/SBT复方制剂(1:1,2:1,4:1,8:1)对鲍曼不动杆菌、表皮葡萄球菌、金黄色葡萄球菌、大肠埃希菌、铜绿假单胞菌、肺炎克雷伯菌等6种临床分离致病菌株(共183株)的最低抑菌浓度(MIC),采用肉汤二倍稀释法测定最小杀菌浓度(MBC),并与单方CRO进行比较.结果:对于鲍曼不动杆菌和产ESBLs大肠埃希菌、肺炎克雷伯菌,4种CRO/SBT不同配比的复方可使耐药率从单用CRO的46.7%～100%下降至4.17%～67%,下降幅度达6～10倍,CRO/SBT(1:1)的MIC50为4～32 mg·L-1,是CRO单方的1/16～1/24;对于不产酶的大肠埃希菌和肺炎克雷伯菌以及耐甲氧西林金黄色葡萄球菌,复方制剂的活性类似于单方.结论:4种配比CRO/SBT对大多数临床分离的致病菌均有较强的体外抗菌活性,明显高于单剂;在复方制剂中,当头孢曲松钠的量一定时,增加舒巴坦钠的量对抗菌活性有一定的增强作用,CRO/SBT(1:1)为强效广谱杀菌复方制剂.     

4种配比的头孢曲松/他唑巴坦的体外抗菌活性

目的研究4种配比头孢曲松/他唑巴坦(CRO/TAZ)及头孢曲松(CRO)单剂对四川地区临床分离致病菌的体外抗菌活性。方法测定525株临床分离致病菌的最低仰菌浓度(MIC)最低杀菌浓度(MBC);采用活菌计数法绘制杀菌曲线;并观察细菌接种量、培养基pH和血清蛋白含量对体外抗菌活性的影响。结果4种配比CRO/TAZ对甲氧西材耐药金菊菌和表皮葡萄球功的MIC50为1~8 mg.L-1,是CRO单剂的1/32~1/256;对产ESBLs大肠埃希菌和肺炎克雷伯菌的MIC50分别降低了8~32倍和16~64倍,MIC90降低了8倍以上;CRO/TAZ(6:1)体外抗菌作用优于头孢哌酮钠-他唑巴坦钠(4:1)或相当;但优于哌拉西林钠-他唑巴坦钠(8:1);4种配比CRO/TAZ均具有很强的杀菌作用,明显优于CRO单剂。结论4种配比CRO/CAZ对大多数临床分离的致病菌均有较强的体外抗菌活性,明显高于单剂。其中,6:1为较合理的配方。     

不同配比头孢噻肟钠/他唑巴坦钠的体外抗菌作用

目的 研究4种不同配比的头孢噻肟钠/他唑巴坦钠(CTX/TAZ)(2:1、4:1、6:1、8:1)及头孢噻肟钠(CTX)单剂对四川地区临床分离致病菌的体外抗菌作用.方法 采用平皿二倍稀释法测定465株临床分离致病菌的最低抑菌浓度(MIC).结果 联合配伍可以使金黄色葡萄球菌(MRSA)、表皮葡萄球菌(MSSE和MRSE)、粪肠球菌、大肠埃希菌(产ESBIz)、铜绿假单胞菌、阴沟肠杆菌、肺炎克雷伯菌(产ESBLs)和鲍曼不动杆菌等从CTX单用的MIC50值128～>256 mg·L-1降至2～64 mg·L-1,下降幅度达4-128倍.结论 不同配比的CTX/TAZ均有强大的杀菌作用,明显优于CTX单剂.6:1的CTX/TAZ复方制剂为较合理的配方组合,具有进一步的研究开发价值.     

头孢噻肟/舒巴坦组方及配比合理性的体外研究进展

我国临床致病菌对头孢噻肟的耐药现象日益严重,产β-内酰胺酶是其主要耐药机制。G-菌主要表达能催化头孢噻肟水解的TEM,CTX-M及SHV型β-内酰胺酶,酶活性能被舒巴坦有效抑制。头孢噻肟/舒巴坦产生抑酶保护作用的配比范围是1∶1~8∶1,最佳配比为1∶1和2∶1。北京、四川、西安三地区进行的体外抗菌试验显示,头孢噻肟/舒巴坦(1∶1~8∶1)对临床耐药菌的抗菌作用明显强于单药,1∶1和2∶1配比的头孢噻肟/舒巴坦的抗菌活性高于4∶1和8∶1。结果表明,头孢噻肟/舒巴坦组方是解决细菌耐头孢噻肟问题的有效方法,其合理配比是2∶1。     

不同配比头孢噻肟与舒巴坦的体外抗菌作用

目的评价头孢噻肟联合舒巴坦复方制剂的抗菌活性及不同配比间的差 异。方法 以平皿二倍稀释法对临床分离的18种636株致病菌进行MIC测 定;以试管二倍稀释法测定34株致病菌的MBC值;以活菌计数法绘制4株致 病菌的杀菌曲线。结果联合头孢噻肟与舒巴坦可显著降低革兰阴性杆菌对 头孢噻肟的耐药率。其中:1:1与2:1配比对大肠埃希菌、肺炎克雷白菌、摩氏摩 根菌、阴沟肠杆菌、产气肠杆菌、粘质沙雷菌及弗氏枸橼酸杆菌的MIC90为2— 32mg·L-1,头孢噻肟高于联合复方制剂(1:1与2:1)4—32倍。头孢噻肟与舒 巴坦4种配比(1:1,2:1,4:1,8:1)对表皮葡萄球菌、肺炎链球菌、化脓性链球菌的 MIC90为0．13-4 mg·L-1,均有较强杀菌作用。其中:1:1与2:1配比对革兰阴 性杆菌的杀菌作用明显优于头孢噻肟。当细菌接种量为1×104～1×107CFU ·mL-1和培养基中的人血清含量对体外抗菌作用无影响。当培养基pH 5．0和 6．0时,头孢噻肟联合制剂对MIC值无影响。结论 头孢噻肟与舒巴坦复合剂 对大多数临床分离致病菌均有较强体外抗菌作用,可降低产酶菌耐药性,2:1 与1:1配比抗菌作用相当。     

哌拉西林／舒巴坦体外抗菌活性研究

目的：研究哌拉西林／舒巴坦（piperacillin/sulbactam)体外抗菌活性。方法：临床分离菌株265株,经VITEK重新鉴定;采用琼脂平板二倍稀释法测定最低抑菌浓度（MIC）;试管二倍稀释法测定最低杀菌浓度（MBC）;菌落计数法缓制杀菌曲线;并测定细菌接种量、培养基pH值以及血清蛋白含量对MIC的影响。结果：不同配比哌拉西林／舒巴坦（1：1、2：1、4：1）对临床常见菌的杀菌活性无明显差异,均强于哌拉西林;对G^-杆菌产酶菌抗菌活性显著高于其它对照药,如替卡西林／克拉维酸和氨苄西林／舒巴坦等。结论：哌拉西林／舒巴坦（1：1、2：1、4：1）是一个有效的β-内酰胺酶抑制剂联合制剂,三种配比的哌拉西林／舒巴坦体外抗菌活性相似,有进一步研究开发价值。     

不同配比头孢呋辛钠/舒巴坦钠的体外药效学研究

目的 评价头孢呋辛钠/舒巴坦钠(cefuroxime/sulbaetam,CXM/SB)的体外抗菌活性.方法 采用平皿二倍稀释法测定CXM/SB对1436株临床分离菌的MIC分布、试管二倍稀释测定最低杀菌浓度、活菌落计数法测定杀菌曲线.结果 CXM/SB1∶1和CXM/SB 2∶1对1436株临床分离菌具有广谱抗菌作用,抗菌活性与哌拉西林/三唑巴坦、头孢哌酮/舒巴坦相近,强于CXM/SB 3∶1、4∶1、8∶1.CXM/SB 1∶1和CXM/SB 2∶1对1109株产β-内酰胺酶菌株的MIC90值比CXM低4～32倍,对产ESBLs大肠埃希菌、肺炎克雷伯菌的MIC90值比CXM低16和8倍.不同pH值、细菌接种量、血清浓度对CXM/SB 2∶1抗金葡菌、大肠埃希菌、肺炎克雷伯菌的活性无明显影响.结论 SB增强了CXM的抗菌活性,CXM/SB 1∶1和CXM/SB 2∶1具有较强和相近的广谱抗菌活性.     

头孢哌酮及不同配比头孢哌酮/舒巴坦的体外抗菌活性研究

目的研究头孢哌酮（CPZ）及不同配比头孢哌酮/舒巴坦（CPZ/SBT）对临床分离致病菌的体外抗菌活性,为临床提供用药依据。方法采用微量稀释法测定CPZ及不同配比CPZ/SBT（1∶1,2∶1）对90株致病菌的最低抑菌浓度（MIC）,并统计MIC范围（MICr）,MIC几何均数（MICg）,50%抑菌浓度（MIC50）、90%抑菌浓度（MIC90）,描记浓度-累积抑菌率曲线。结果不同配比CPZ/SBT的MICg,MIC50,MIC90均较CPZ明显下降,浓度-累积抑菌率曲线比CPZ左移,但不同配比CPZ/SBT之间无明显差别。结论CPZ/SBT可明显提高CPZ的抗菌作用,1∶1配比的CPZ/SBT与2∶1配比者抗菌活性相似,使用2∶1配比的CPZ/SBT较1∶1配比者更安全、经济。     

The effect of sulbactam on the in vitro activity of mezlocillin, piperacillin and cefotaxime]

The in vitro activity of mezlocillin (MZL, CAS 51481-65-3), piperacillin (PIP, CAS 61477-96-1) and cefotaxim (CTX, CAS 63527-52-6) alone and in combination with sulbactam (SBT; CAS 68373-14-8) against mezlocillin-resistant pathogens was determined in a multicenter study. A total of 870 strains were investigated (481 Enterobacteriaceae, 57 Pseudomonas aeruginos, 41 Acinetobaster spp., 194 Bacteroides fragilis, and 97 Staphylococcus spp.). Determinations of MIC were performed according to DIN-guidelines (agar-dilution method for aerobes and microbroth-dilution method for anaerobes). Sulbactam was added in fixed concentrations of 5 mg/l and 10 mg/l. In all sulbactam-combinations examined mean MIC as well as MIC50 and MIC90 were reduced compared to the respective values for the antibiotics alone. Consequently, percentages of susceptible strains increased significantly: i.e. for Enterobacteriaceae: MZL 1% vs. MZL + 10 mg/l SBT 53%; PIP 4% vs. PIP + 10 mg/l SBT 54%; CTX 52% vs. CTX + 10 mg/l SBT 68%. The effect of sulbactam was most pronounced in Bacteroides spp. with an increase in susceptible strains from 2% to 97% for MZL, from 6% to 95% for PIP and from 7% to 98% for CTX. The results indicate that by adding sulbactam the in vitro activity of mezlocillin, piperacillin and cefotaxim against resistant pathogens is augmented significantly. In addition, the spectrum of antibacterial activity is extended to anaerobic pathogens such as Bacteroides spp. The availability of sulbactam as a monosubstance for combination with various beta-lactam-antibiotics thus represents a useful improvement of therapeutic options in bacterial infections.     

莫西沙星联用头孢哌酮舒巴坦对8种耐药菌的抗菌效应研究

目的探讨莫西沙星与头孢哌酮舒巴坦联用对临床常见耐药菌的抗菌效果。方法采用Vitek-32型全自动细菌鉴定仪,测定莫西沙星与头孢哌酮舒巴坦单用和联用分别对60株金黄色葡萄球菌、大肠埃希菌（ATCC25922）、铜绿假单胞菌、肺炎克雷伯菌和30株粪肠球菌、大肠埃希菌（ATCC35218）、阴沟肠杆菌及幽门螺杆菌的最低抑菌浓度（MIC）,并计算联合药敏指数（FIC值）。结果两药联用对临床分离的360株常见耐药致病菌的MIC均明显降低且抗菌作用增强,对金黄色葡萄球菌、粪肠球菌和幽门螺杆菌的体外抗菌作用为协同作用,对大肠埃希菌（ATCC25922）、铜绿假单胞菌、肺炎克雷伯菌、大肠埃希菌（ATCC35218）和阴沟肠杆菌均为相加作用。结论研究结果对指导医院常见耐药菌感染的治疗具有重要意义。     

注射用头孢噻肟钠他唑巴坦钠的体外抗菌活性研究

目的研究头孢噻肟钠他唑巴坦钠复方制剂对产β-内酰胺酶的头孢噻肟耐药[最小抑菌浓度(MIC)≥64μg/ml]临床分离菌的体外抗菌活性。方法采用琼脂二倍稀释法测定了不同配比头孢噻肟钠他唑巴坦钠复方制剂(CTX/TAZ1∶1、2∶1、4∶1、8∶1、16∶1)的体外MIC值,并与哌拉西林钠他唑巴坦钠(PIP/TAZ8∶1)、头孢哌酮钠舒巴坦钠(CPZ/SBT1∶1)进行比较。结果与头孢噻肟钠单独用药相比,头孢噻肟钠他唑巴坦钠复方制剂对产酶的大肠埃希菌、肺炎克雷伯杆菌、醋酸钙不动杆菌、阴沟肠杆菌、产气肠杆菌、黏质沙雷菌和异型枸橼酸杆菌的抗菌活性明显增强,MIC50至单用头孢噻肟钠的1/2～1/64。头孢噻肟钠他唑巴坦钠复方制剂对产酶的甲氧西林耐药金黄色葡萄球菌(MRSA)、甲氧西林耐药表皮葡萄球菌(MRSE)、铜绿假单胞菌的抗菌活性没有明显影响,MIC50不变或降低至1/2。他唑巴坦钠对头孢噻肟抗菌活性的增强作用随着他唑巴坦钠的加入量增加而增强,其中CTX/TAZ4∶1对大肠埃希菌(包括产超广谱β-内酰胺酶ESBLs)、肺炎克雷伯杆菌(包括产ESBLs)、醋酸钙不动杆菌、阴沟肠杆菌、产气肠杆菌、黏质沙雷菌和异型枸橼酸杆菌的MIC50分别为4、4、64、32、8、4和8μg/ml,其抗菌活性比CTX单独用药高,MIC50为单独用药的1/4～1/32。头孢噻肟/他唑巴坦4∶1对大肠埃希菌、肺炎克雷伯杆菌的抗菌活性优于哌拉西林/他唑巴坦、头孢哌酮/舒巴坦,MIC50为后两种组合的1/4～1/8。头孢噻肟/他唑巴坦4∶1对醋酸钙不动杆菌、阴沟肠杆菌、异型枸橼酸杆菌、产气肠杆菌和黏质沙雷菌的抗菌活性稍强于哌拉西林/他唑巴坦,弱于或接近于头孢哌酮/舒巴坦。结论他唑巴坦钠的加入可以有效增强头孢噻肟对除MRSA、MRSE和铜绿假单胞菌外的受试菌的敏感性。     

头孢哌酮钠/舒巴坦钠对铜绿假单胞菌的最低抑菌浓度和防突变浓度研究

目的:研究头孢哌酮钠/舒巴坦钠对铜绿假单胞菌的最低抑菌浓度(MIC)和防突变浓度(MPC),为控制细菌耐药提供参考。方法:采用肉汤法富集铜绿假单胞菌标准菌株及14株临床分离菌株,采用琼脂平板稀释法考察头孢哌酮钠/舒巴坦钠对铜绿假单胞菌的MIC、MPC值,计算MIC90、MPC90、选择指数(SI)。结果:头孢哌酮钠/舒巴坦钠对15株铜绿假单胞菌的MIC、MPC均为4³2μg/ml,MIC90、MPC90均为32μg/ml,SI为1。结论:头孢哌酮钠/舒巴坦钠在临床治疗浓度下不容易引起铜绿假单胞菌耐药突变菌株的富集。     

头孢拉宗等9种抗菌药物对产ESBLs大肠埃希菌和肺炎克雷伯菌的体外抗菌活性研究

目的:对比研究头孢拉宗等9种抗菌药物对产超广谱β-内酰胺酶(ESBLs)大肠埃希菌以及肺炎克雷伯菌的体外抗菌活性。方法:采用琼脂平板二倍稀释法测定头孢拉宗等9种抗菌药物对临床分离的产ESBLs大肠埃希菌115株、肺炎克雷伯菌30株的最低抑菌浓度(MIC)。结果:产ESBLs大肠埃希菌和肺炎克雷伯菌对亚胺培南/西司他丁(100%和96.7%)、美罗培南的敏感率最高(100%和96.7%),对头孢拉宗(98.3%和93.3%)、头孢美唑(93.0%和96.7%)和阿米卡星(95.7%和96.7%)的敏感率较高,对哌拉西林/他唑巴坦(92.1%和60.0%)、头孢他啶(62.6%和73.3%)比较敏感,但对头孢噻肟(3.5%和0)、头孢哌酮/舒巴坦(43.5%和36.7%)的耐药率很高。结论:头孢拉宗对产ESBLs的大肠埃希菌和肺炎克雷伯菌均有很强的体外抗菌活性。     

Antimicrobial activity of sulbactam/cefoperazone. Comparison with other new cephems

Antimicrobial activities of sulbactam/cefoperazone (SBT/CPZ) against 50 fresh clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter spp., Serratia marcescens, Proteus mirabilis, Proteus vulgaris and Pseudomonas aeruginosa were compared to those of CPZ, Cefotiam (CTM), Cefotaxime (CTX) and Latamoxef (LMOX). Minimal inhibitory concentrations (MIC's) of SBT and CPZ mixed in a ratio of 1:1 were determined by the dilution method using Mueller-Hinton agar and expressed by absolute concentrations of CPZ. Antimicrobial activities of SBT/CPZ against principally penicillinase (PCase) producing bacteria, i.e., S. aureus, E. coli, K. pneumoniae, P. mirabilis, were superior to those of CPZ alone. The presence of SBT in concentrations around 0.39 approximately 1.56 micrograms/ml clearly enhanced CPZ's antimicrobial activities against these PCase producing strains. The synergistic antimicrobial effects of SBT in combination with CPZ were less pronounced against principally cephalosporinase (CEPase) producing bacteria, i.e., C. freundii, Enterobacter spp., S. marcescens, P. vulgaris, and P. aeruginosa, and exerted with SBT at concentrations around 3.13 approximately 12.5 micrograms/ml. Comparative antimicrobial activities indicated by MIC80's of tested agents showed that SBT/CPZ had more stable activities against bacteria ranging from Gram-positive to Gram-negative bacteria than CTM, CTX and LMOX. MIC's of SBT/CPZ were higher than 25 micrograms/ml against 8% of S. aureus, 18% of C. freundii, 10% of Enterobacter spp., 26% of S. marcescens, 2% of P. vulgaris, and 18% of P. aeruginosa. These resistant strains against which the addition of SBT showed no synergism, may possess other mechanism of resistance than beta-lactamase production. It is concluded that the presence of CPZ resistant strains is an actual current problem and not an imaginary future problem, and that the number of resistant strains against other new cephems which have different chemical structure from CPZ is increasing. When these present bacteriological environments are considered, the appearance of SBT/CPZ in the clinical practice is timely and meaningful.     

Yearly changes in antibacterial activities of cefozopran against various clinical isolates between 1996 and 2001--I. Gram-positive bacteria

The in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates obtained between 1996 and 2001 were yearly evaluated and compared with those of other cephems, oxacephems, carbapenems, and penicillins. A total of 1,274 strains in 15 species of Gram-positive bacteria were isolated from the clinical materials annually collected from January to December, and consisted of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Staphylococcus haemolyticus, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus faecium, Enterococcus avium, and Peptostreptococcus spp. CZOP possessed stable antibacterial activities against all strains tested throughout 6 years. The MIC90 of CZOP against MRSA and S. haemolyticus tended to decrease while against S. pneumoniae and Peptostreptococcus spp., tended to increase year by year. However, the MIC90 just changed a little and were consistent with the results from the studies performed until the new drug application approval. Increases in the MIC90 against S. pneumoniae were also observed with ceftazidime (CPR), cefepime (CFPM), flomoxef (FMOX), sulbactam/cefoperazone (SBT/CPZ), and imipenem (IPM). Increases in the MIC90 against Peptostreptococcus spp. were also observed with FMOX, SBT/CPZ, and IPM. In conclusion, the annual antibacterial activities of CZOP against the Gram-positive bacteria did not considerably change. It, therefore, was suggested that CZOP had maintained high antibacterial activity during 6 years of post marketing.