舒巴坦与第三代头孢菌素联合对第三代头孢菌素耐药菌的体外抗菌作用研究

目的：探讨舒巴坦与头孢他啶、头孢噻肟、头胞呋辛1：1联合对头孢他啶或头孢呋辛耐药的革兰阴性杆菌及金葡球菌的体外抗菌增效作用。方法：用平皿二倍稀释法测定了舒巴坦与头孢他啶、头孢噻肟、头孢呋辛1：1联合的体外抗菌作用。结果：舒巴坦可以增强头孢他啶、头孢噻肟及头孢呋辛对革兰阴性杆菌的体外抗菌活性。舒巴坦可以使头孢他啶对大肠杆菌、阴沟肠杆菌、弗劳地枸橼酸杆菌、不动杆菌属、铜绿假单胞菌的MIC90降低4倍;使头孢噻肟对大肠杆菌、阴沟肠杆菌、弗劳地枸橼酸杆菌、不动杆菌属的MIC90降低2－4倍,但对金葡球菌、肠球菌及嗜麦芽窄食单胞菌无明显的增效作用。38.4%的头孢他啶耐药的大肠杆菌、45.3%的对头孢他啶耐药的阴沟肠杆菌、66.6%的对头孢他啶耐药的弗劳地枸橼酸杆菌及60％的对头孢他啶耐药的不动杆菌属对舒巴坦与头孢他啶（1：1）的联合制剂敏感。结论：舒巴坦与头孢他啶联合对头孢他啶耐药菌有30％－40％的抗菌增效作用。     

阴沟肠杆菌Amp C酶的特性研究

本文对阴沟肠杆菌ＡｍｐＣ酶进行了以下５个方面研究。其内容和结果分别为：（１）联合药敏实验：用平皿二倍稀释法研究第四代头孢菌素头孢吡肟,第三代头孢菌素头孢他啶、头孢噻肟、头孢呋辛与－β－内酰胺酶抑制剂舒巴坦联合对３４株头孢他啶耐药菌,６株头孢他啶中敏菌及１５株头孢他啶敏感菌的体外抗菌活性。结果表明舒巴坦使头孢他啶对３２．７％（１８／５５）的阴沟肠杆菌的抗菌作用有明显抗菌增效作用。９６．４％（５３／５５）的阴沟肠杆菌对第四代头孢菌素头孢吡肟敏感。（２）酶稳定性实验：紫外测定法测定４株标准菌和６株临床分离菌产生的ＡｍｐＣ酶对β－内酰胺类抗生素的水解率。结果表明阴沟肠杆菌产生的β－内酰胺酶对第一代头孢菌素头孢唑林、头孢氨苄,第二代头孢菌素头孢克洛,第三代头孢菌素头孢哌酮及青霉素、氨苄西林、哌拉西林的水解率高,对第二代头     

注射用头孢哌酮／他唑巴坦的体外抗菌活性研究

目的：评价头孢哌酮／他唑巴坦（4：1和8：1）、头孢哌酮／舒巴坦（1：1和2：1）的抑酶增效作用,并比较同类复方制剂在临床常用量时的体外抗菌效果。方法：采用琼脂二倍稀释法对409株临床分离株进行药物敏感测定。结果：头孢哌酮／他唑巴坦（4：1和8：1）、头孢哌酮／舒巴坦（1：l和2：1）联合应用对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌等革兰阳性菌的MIC50／MIC90均较头孢哌酮钠单用时降低2～4倍。对大肠埃希菌（包括产ESBLs）、肺炎克雷伯菌（包括产（ESBLs）、铜绿假单胞菌、阴沟肠杆菌、鲍曼不动杆菌等革兰阴性杆菌的MIC50／MIC90分别较头孢哌酮钠单用时降低2～64倍和2～8倍,尤其对产ESBLs的大肠埃希菌和肺炎克雷伯菌其MIC50／MIC990也分别降低8～32倍和2—8倍。同类复方制剂对上述革兰阳性菌和革兰阴性杆菌的MIC50／MIC90在临床常用量的1／256—1／65536倍,MIC50和MIC90较按常规试验配比组分别降低3～33倍和4～87倍。结论：头孢哌酮与他唑巴坦或舒巴坦联合应用可不同程度地提高头孢哌酮的体外抗菌活性,头孢哌翮／他唑巴坦4：1和8：1的体外抗菌活性基本相当,均优于头孢哌酮／舒巴坦1：1和2：1。4种同类复方制剂的体外抗菌活性,注射用头孢哌酮／他唑巴坦亦优于注射用头孢哌酮／舒巴坦。     

哌拉西林钠-舒巴坦钠(4:1)的体外抗菌活性

目的 研究哌拉西林钠／舒巴坦钠（4：1）体外抗菌活性。方法 用琼脂平板二倍稀释法测定最低抑菌浓度（MIC）。结果 哌拉西林-舒巴坦复方制剂（4：1）对革兰阳性菌和革兰阴性菌均有较好抗菌活性。尤其对产酶甲氧西林敏感的金黄色葡萄球菌（MSSA）和甲氧西林敏感的表皮葡萄球菌（MSSE）、产酶流感嗜血杆菌和卡他莫拉菌、不产超广谱β内酰胺酶（ESBLs）与产ESBLs的大肠埃希菌和肺炎克雷伯菌、易产染色体诱导酶的阴沟肠杆菌、铜绿假胞菌和鲍曼不动杆菌的抗菌作用优于哌拉西林钠，其MIC50或MIC90为哌拉西林钠的1／2～1／32和1／2～1／64。产ESBLs的大肠埃希菌对哌拉西林钠／舒巴坦钠（4：1）、头孢哌酮钠／舒巴坦钠、哌拉西林／他唑巴坦钠的敏感性分别为60．0％，66．7％和76．7％；而肺炎克雷伯菌的敏感性分别为56．7％，63．3％和63．3％；铜绿假胞菌的敏感性分别为72．0％，72．0％和76．0％；鲍曼不动杆菌的敏感性分别为76．0％，82．0％和52．0％。结论 哌拉西林钠／舒巴坦钠是有效的β内酰胺酶抑制剂的复合制剂。     

20株阴沟肠杆菌耐药性及耐复方磺胺甲噁唑相关基因研究

目的 探讨临床分离的阴沟肠杆菌耐药性和耐复方磺胺甲噁唑（SMZ／TMP）相关基因存在状况。方法 采用ATB药敏试验板微量肉汤法测定临床分离的20株阴沟肠杆菌对20种抗菌药物的敏感性，采用PCR检测耐复方磺胺甲略唑相关基因sull、dfrAl和dfrA17。结果 20株菌对亚胺培南和美罗培南均敏感，对其他抗菌药物的不敏感率在25．0％～100％之间。sull、dfrA1和dfrA17基因阳性率为85．0％（17／20）、5．0％（1／21）、60．0％（12／20）。结论 阴沟肠杆菌具明显的多重耐药特征。耐复方磺胺甲口恶唑相关基因携带率很高。     

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。     

头孢唑兰对临床分离菌株体外抗菌作用评价

目的：评价头孢唑兰对临床分离菌株的体外抗菌作用,为头孢唑兰的临床使用提供参考依据。方法：用浊度法测定头孢唑兰对临床分离的无乳链球菌、甲氧西林敏感的金黄色葡萄球菌（MSSA）、甲氧西林敏感表皮葡萄球菌（MSSE）、肺炎链球菌、粪肠球菌、化脓性链球菌、大肠埃希菌、肺炎克雷伯菌、流感嗜血杆菌、阴沟肠杆菌、奇异变形杆菌、铜绿假单胞菌、产气肠杆菌等的最小抑菌浓度（MIC）和最小杀菌浓度（MBC）,平行试验3次,观察头孢唑兰培养液的的浊度。结果：头孢唑兰对化脓性链球菌、肺炎链球菌、无乳链球菌、MSSE、MSSA、粪肠球菌6种临床分离G~＋菌株的MIC分别为0.064,0.125,0.125,0.5,2,8μg·ml~（-1）,MBC分别为0.125,0.25,0.25,1,4,16μg·ml~（-1）;对肺炎克雷伯菌、大肠埃希菌、奇异变形杆菌、流感嗜血杆菌、产气肠杆菌、铜绿假单胞菌、阴沟肠杆菌7种临床分离G~-菌株的MIC分别为0.125,0.125,0.25,1,1,8,32μg·ml~（-1）,MBC分别为0.25,0.25,0.5,2,2,16,64μg·ml~（-1）。结论：头孢唑兰具有较强的抑菌及杀菌作用。     

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。     

ESBLs在大肠埃希菌、肺炎克雷伯菌和阴沟肠杆菌中的检出率及耐药情况比较

目的检测我国大肠埃希菌、肺炎克雷伯菌和阴沟肠杆菌中超广谱β-内酰胺酶(ESBLs)产生及耐药情况。方法对2000-2001年中国细菌耐药监测研究所收集的来自9座城市13家医院的大肠埃希菌、肺炎克雷伯菌和阴沟肠杆菌采用平皿二倍稀释法测定抗菌药物对各种致病菌的MIC值，计算MIC50与MIC90，并按NCCLS2002规定的临界浓度，求出各类细菌对所测定的各种抗菌药物的耐药率(R％)。以纸片扩散法确证试验检测产ESBLs大肠埃希菌和肺炎克雷伯菌，以三维试验检测产ESBLs和AmpC酶的阴沟肠杆菌。结果在总共341株大肠埃希菌和212株肺炎克雷伯菌中共检测到产ESBLs菌100株，检出率18．1％(100／553)。其中产ESBLs大肠埃希菌63株，检出率18．5％(63／341)；产ESBLs肺炎克雷伯菌37株，检出率17．5％(37／212)。产ESBLs菌株对β-内酰胺类抗生素的耐药率明显高于非ESBLs菌株。酶抑制剂联合制剂头孢哌酮／舒巴坦、第四代头孢菌素头孢吡肟和碳青霉烯类对产ESBLs菌株有较好作用。81株阴沟肠杆菌中，28株产ESBLs，检出率34．6％；31株产AmpC酶，检出率38．3％；14株同时产生此二类酶，检出率17．3％。在对头孢曲松中介的14株阴沟肠杆菌中，AmpC酶检出率为42．9％(6／14)，而ESBLs的检出率高达92．9％(13／14)，是AmpC酶检出率的两倍多。但在对头孢曲松耐药的27株阴沟肠杆菌中．情况刚好相反，AmpC酶的检出率为88．9％(24／27)，是ESBLs检出率(40．7％，11／27)的两倍多。头孢噻肟中介和耐药株中两酶的检出情况与头孢曲松相似。头孢他啶只有1株中介株，耐药株中AmpC酶检出率(78．4％，29／37)约是ESBLs检出率(56．8%，21／37)的1．4倍。若将敏感和中介株合并计算可见，头孢他啶敏感和中介株中两酶的检出率明显低于头孢曲松和头孢噻肟。结论①细菌耐药研究显示ESBLs在大肠埃希菌和肺炎克雷伯菌中的检出率为18．1％；②ESBLs在我国阴沟肠杆菌中有很高的检出率；③在阴沟肠杆菌中，对头孢曲松和头孢噻肟中介的菌株，以产ESBLs为主，而耐药菌株以产AmpC酶为主。     

101株阴沟肠杆菌的耐药性分析

目的：调查分析阴沟肠杆菌对临床常用抗生素的耐药情况。方法：对四川大学华西医院2001年4月－2002年11月从临床分离的101株阴沟肠杆菌采用琼脂平皿对倍稀释法测定12种抗生素的最低抑菌浓度（MIC），分析耐药情况。结果：阴沟肠杆菌对氨苄西林、头孢呋辛的耐药率高达99.00%、87.13%，对第三代头孢菌素、氟喹诺酮类的耐药率高于50％，对关孢哌酮／舒巴坦、头孢吡肟、阿米卡星的耐药率低于40％，亚胺培南对90％以上的分离株具有抗菌活性。氟喹诺酮类药物的交叉耐药严重。结论：阴沟肠杆菌耐药水平高，多重耐药现象普遍存在。亚胺培南对其抗菌活性最强。     

Susceptibility of clinical isolates to aztreonam

In vitro antibacterial activities of 9 antibiotics including aztreonam (AZT) against clinically isolated Gram-negative bacteria were determined using MIC-2000 plus system. Bacteria were isolated from clinical materials in Saga Medical School during a period from May 1987 to March 1988. Summarized results were as follows: 1. AZT showed excellent antibacterial activities against Escherichia coli, Klebsiella pneumoniae, Proteus sp. and Haemophilus influenzae, and MIC80 values of AZT against these organisms were lower than 0.20 microgram/ml. 2. Antibacterial activities of AZT were superior to cephem antibiotics compared against Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii and Serratia marcescens. 3. The MIC50 and MIC80 of AZT against Pseudomonas aeruginosa were 12.5 micrograms/ml and 25 micrograms/ml, respectively. 4. AZT did not show any antibacterial activity against Acinetobacter sp. and Xanthomonas maltophilia.     

Susceptibility of clinically isolated strains to aztreonam

In vitro antibacterial activities of aztreonam (AZT) and cephems against clinically isolated 334 strains were investigated. The results obtained in the study are summarized as follows: 1. AZT showed excellent antibacterial activities against clinically isolated 334 strains. 2. AZT showed potent activities against Escherichia coli, Klebsiella pneumoniae, Proteus spp., Enterobacter aerogenes and Citrobacter freundii. 3. Antibacterial activities of AZT were superior against Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa to those of cephems.     

Yearly changes in antibacterial activities of cefozopran against various clinical isolates between 1996 and 2001--II. Gram-negative 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 and carbapenems. A total of 3,245 strains in 32 species of Gram-negative bacteria were isolated from the clinical materials annually collected from January to December, and consisted of Moraxella subgenus Branhamella catarrhalis, Escherichia coli, Citrobacter freundii, Citrobacter koseri, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Proteus mirabillis, Proteus vulgaris, Morganella morganii, Providencia spp. (P. alcalifaciens, P. rettgeri, P. stuartii), Pseudomonas aeruginosa, Pseudomonas putida, Burkholderia cepacia, Stenotrophomonas maltophilia, Haemophilus influenzae, Acinetobactor baumannii, Acinetobactor lwoffii, Bacteroides fragilis group (B. fragilis, B. vulgatus, B. distasonis, B. ovatus, B. thetaiotaomicron), and Prevotella spp. (P. melaninogenica, P. intermedia, P. bivia, P. oralis, P. denticola). CZOP possessed stable antibacterial activities against M. (B.) catarrhalis, E. coli, C. freundii, C. koseri, K. pneumoniae, K. oxytoca, E. aerogenes, E. cloacae, S. marcescens, P. mirabilis, P. vulgaris, M. morganii, Providencia spp., P. aeruginosa, and A. lwoffii throughout 6 years. The MIC90 of CZOP against those strains were consistent with those obtained from the studies performed until the new drug application approval. On the other hand, the MIC90 of CZOP against H. influenzae yearly obviously increased with approximately 64-time difference during the study period. The MIC90 of cefpirome, cefepime, and flomoxef against H. influenzae also yearly tended to rise. The present results demonstrated that CZOP had maintained the antibacterial activity against almost Gram-negative strains tested. However, the decrease in antibacterial activities of CZOP against B. cepacia, and H. influenzae was suggested.     

Susceptibility of clinically isolated bacterial strains to imipenem/cilastatin sodium

In vitro antibacterial activities of imipenem/cilastatin sodium (imipenem) and other beta-lactams against clinically isolated 353 bacterial strains were investigated. The results obtained in this study are summarized as follows: 1. Imipenem (IPM) showed potent antibacterial activities against Gram-positive cocci such as Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus agalactiae. 2. IPM had inferior or equivalent antibacterial activities to beta-lactams against clinically isolated Enterobacteriaceae, that is, Escherichia coli, Citrobacter freundii, Klebsiella pneumoniae, Serratia marcescens, Enterobacter cloacae, Enterobacter aerogenes and Proteus spp. 3. IPM showed potent antibacterial activities against clinically isolated Pseudomonas aeruginosa, Acinetobacter anitratus but not against Xanthomonas maltophilia.     

Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--II. Gram-negative bacteria

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, carbapenems, monobactams, and penicillins. Changes in CZOP susceptibility among bacteria were also evaluated with the bacterial resistance ratio calculated from the breakpoint MIC. Twenty-five species (4,154 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2001, and consisted of Moraxella (Branhamella) catarrhalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Serratia liquefaciens, Citrobacter freundii, Citrobacter koseri, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia spp., Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida, Acinetobacter baumannii, Acinetobacter Iwoffii, Burkholderia cepacia, Stenotrophomonas maltophilia, Bacteroides fragilis group, and Prevotella/Porphyromonas. CZOP preserved its antibacterial activity against M. (B.) catarrhalis (MIC90: 4 micrograms/mL) and showed comparable activity to carbapenems against H. influenzae (MIC90: 1 microgram/mL). The antibacterial activity of CZOP against E. coli was preferable (MIC90: 0.125 microgram/mL) and comparable to those of cefpirome (CPR), cefepime (CFPM), and imipenem (IPM). The MIC90 of CZOP against K. pneumoniae and K. oxytoca was 1 and 0.25 microgram/mL, respectively. The MIC90 of CZOP against E. cloacae increased during 6 years (32 to 128 micrograms/mL). The antibacterial activity of CZOP against E. aerogenes was preferable (MIC90: 1 microgram/mL). The antibacterial activities of CZOP against S. marcescens and S. liquefaciens were relatively potent (MIC90: 0.5 and 0.25 microgram/mL) and comparable to those of CPR, CFPM, and carumonam. CZOP preserved comparable antibacterial activity to CPR against C. freundii and C. koseri (MIC90: 8 and 0.125 micrograms/mL). The MIC90 of CZOP against P. mirabilis, P. vulgaris, and M. morganii was 0.25, 16, and 2 micrograms/mL, respectively. The antibacterial activity of CZOP against Providencia spp. was moderate (MIC90: 64 micrograms/mL). The antibacterial activity of CZOP against P. aeruginosa was the most potent (MIC90: 16 micrograms/mL) among the test agents and comparable to those CFPM, IPM, and MEPM. CZOP had low activity against P. fluorescens and P. putida (MIC90: 128 micrograms/mL). The antibacterial activity of CZOP against A. baumannii was comparable to those of ceftazidime (CAZ), CPR and CFPM (MIC90: 32 micrograms/mL) and against A. lwoffii was moderate (MIC90: 64 micrograms/mL). Most of the test agents including CZOP had low antibacterial activity against B. cepacia, S. maltophilia, and B. fragilis group. The MIC90 of CZOP against Prevotella/Porphyromonas was 64 micrograms/mL. Bacterial cross-resistance ratio between CZOP and other agents was low in most of the species, ranging from 0.0 to 15.1%. In non-glucose fermentative bacteria, however, the bacterial cross-resistance ratio between CZOP and CFPM, CAZ, CPR, or IPM was high, being 36.8%, 28.0%, 38.7%, or 31.1%, respectively. In conclusion, the 6-year duration study suggested that the antibacterial activity of CZOP against E. cloacae possible decreased, but against other Gram-negative bacteria was consistent with the study results obtained until the new drug application approval.     

Antibacterial activities of sisomicin against fresh clinical isolates]

To investigate antibacterial activities of sisomicin (SISO), MICs of SISO as well as other aminoglycosides (AGs) were determined against many clinical isolates which were obtained in 1991. Results are summarized below: 1. No SISO-resistant strains were observed among isolates of Escherichia coli, Citrobacter diversus, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Proteus mirabilis and Morganella morganii. 2. In comparison with the results of our previous study against isolates obtained in 1986, the rate of methicillin-resistant Staphylococcus aureus (MRSA) was higher, and SISO-resistant strains were observed at a high rate among the MRSA. Also, SISO-resistant strains of Serratia marcescens increased. However, the rate of SISO-resistant strains of Pseudomonas aeruginosa decreased, and among Citrobacter freundii, Enterobacter cloacae and Proteus vulgaris, SISO-resistant strains did not increase over the years. 3. MICs of SISO against Providencia rettgeri and Providencia stuartii were high, suggesting that antibacterial activities of SISO was weak against genus Providencia. 4. For comparison, according to MICs of ofloxacin and imipenem, new quinolone-resistant strains were observed at a high rate among various organisms, and carbapenem-resistant strains were observed at a high rate among S. marcescens and P. aeruginosa. 5. SISO is still one of the useful AGs in the 1990's since it maintains its strong antibacterial activities against most clinical isolates obtained in recent years and its potential as a combination drug with beta-lactams is being reported.     

Synergistic action of cefodizime with other antimicrobial agents on clinically isolated microorganisms. II. Synergistic action with sisomicin]

Cefodizime (CDZM) possesses a broad antimicrobial spectrum and a relatively long half life in the blood. In addition, it shows excellent therapeutic efficacies in the treatment of infections in leukopenic animal models, hence it is expected that CDZM may have good efficacies against various infections in immunocompromised hosts. In the meantime, sisomicin (SISO) not only has strong antibacterial activities against Gram-negative rods (GNR), but has relatively low nephrotoxicity and ototoxicity. Thus, we examined antibacterial effectiveness of the combination of CDZM and SISO against clinical isolates in vitro. 1. Antibacterial effects of CDZM+SISO combination were examined using SISO susceptible strains of Escherichia coli, Citrobacter freundii, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus vulgaris, Morganella morganii and Pseudomonas aeruginosa. Observations that the combination of the 2 drugs showed FIC indices between less than 0.5-less than 1.0 against most of these strains at SISO concentrations of 1 MIC or sub MIC levels strongly suggested the presence of a synergistic action between the 2 drugs against SISO susceptible strains of GNR. 2. Of the strains tested, 10% of C. freundii, 6.7% of E. cloacae, 63.3% of S. marcescens, 23.3% of P. vulgaris and 18.0% of P. aeruginosa were found to be resistant to SISO, and little synergistic effect of the 2 drugs was observed against these strains. 3. As the synergistic effect of the 2 drugs against GNR was observed against SISO susceptible strains including those which were resistant to CDZM, but not against those strains which were resistant to SISO, it seems reasonable to conclude that the appearance of the synergistic effect between the 2 drugs depends on the activity of SISO.     

The in vitro activity of sulbactam combined with third generation cephalosporins against third generation cephalosporin-resistant bacteria

The in vitro activity of the beta-lactamase inhibitor sulbactam combined with cefuroxime, cefotaxime or ceftazidime in the ratio of 1:1 was studied against ceftazidime- or cefuroxime-resistant Gram-negative rods and Staphylococcus aureus. Sulbactam enhanced the antibacterial activities of cefuroxime, cefotaxime and ceftazidime against Gram-negative rods. The MIC(90) of ceftazidime against Escherichia coli, Enterobacter cloacae, Citrobacter freundii, Acinetobacter spp. and Pseudomonas aeruginosa was reduced 4-fold and that of cefotaxime against E. coli, E. cloacae, C. freundii and Acinetobacter spp. reduced by 2-4-fold. However, sulbactam did not enhance the activities of cefuroxime, cefotaxime or ceftazidime against S. aureus, enterococci and Stenotrophomonas maltophilia. With the combination of sulbactam and ceftazidime at the ratio of 1:1, 38.4% of E. coli, 45.3% of E. cloacae, 66.6% of C. freundii and 60% of Acinetobacter spp. initially resistant to ceftazidime became susceptible.     

Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--II. Gram-negative bacteria

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, penicillins, monobactams, and carbapenems. Changes in CZOP susceptibility for the bacteria were also evaluated with the bacterial resistance ratio calculated with the breakpoint MIC. Twenty-five species (3,362 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2000, and consisted of Moraxella (Branhamella) catarrhalis (n = 136), Haemophilus influenzae (n = 289), Escherichia coli (n = 276), Klebsiella pneumoniae (n = 192), Klebsiella oxytoca (n = 157), Enterobacter cloacae (n = 189), Enterobacter aerogenes (n = 93), Serratia marcescens (n = 172), Serratia liquefaciens (n = 24), Citrobacter freundii (n = 177), Citrobacter koseri (n = 70), Proteus mirabilis (n = 113), Proteus vulgaris (n = 89), Morganella morganii (n = 116), Providencia spp. (n = 41), Pseudomonas aeruginosa (n = 290), Pseudomonas fluorescens (n = 56), Pseudomonas putida (n = 63), Acinetobacter baumannii (n = 146), Acinetobacter lwoffii (n = 34), Burkholderia cepacia (n = 101), Stenotrophomonas maltophilia (n = 169), Bacteroides fragilis group (n = 196), and Prevotella/Porphyromonas (n = 173). An antibacterial activity of CZOP against E. coli, K. pneumoniae, K. oxytoca, and S. marcescens was potent and consistent with or more preferable than the study results obtained until the new drug application approval. MIC90 of CZOP against M.(B.) catarrhalis, C. koseri, and P. aeruginosa was not considerably changed and consistent with the study results obtained until the new drug application approval. MIC90 of CZOP against E. cloacae, E. aerogenes, and P. mirabilis increased year by year. The increase in MIC90 of CZOP against E. aerogenes and P. mirabilis, however, was not considered to be an obvious decline in susceptibility. In contract, the susceptibility of E. cloacae to CZOP was suspected to be decreasing because this species showed 20.6% resistance to CZOP. MIC90 of CZOP against C. freundii was variably changed or not one-sidedly, but was higher than the values obtained until the new drug application approval. Additionally, MIC90 of CZOP against H. influenzae was stable during 5 years except being higher in 1999, and, as a whole, was a little higher than the values obtained until the new drug application approval. An antibacterial activity of CZOP against P. fluorescens, P. putida, B. cepacia, S. maltophilia, B. fragilis group, and Prevotella/Porphyromonas was weak like the other cephems. Changes in MIC90 of CZOP against the other bacteria were 2 tubes or more through 5-year study period, but did not tend towards a unilateral direction as meaning a decline in susceptibility.     

Antibacterial activity of aztreonam: a synthetic monobactam. A comparative study with thirteen other antibiotics

The in vitro activity of aztreoman (SQ 26, 776), a new monocyclic beta-lactam antimicrobial agent, was determined against 1720 bacteria, all clinical isolates, and compared with that of thirteen beta-lactam and aminoglycoside antibiotics. Aztreonam inhibited 90% of Citrobacter diversus, Citrobacter freundii, Enterobacter agglomerans, E. coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii, Proteus rettgeri, Proteus vulgaris and Salmonella sp. by less than or equal to 0.4 micrograms ml-1. This activity was superior to moxalactam, piperacillin, cefamandole, cefoperazone, cefoxitin, cefsulodin, ceftazidime and aminoglycoside antibiotics. Aztreonam was as active as moxalactam against Enterobacter aerogenes, Enterobacter cloacae and Shigella species. Pseudomonas aeruginosa strains resistant to moxalactam, piperacillin, cefamandole, cefoperazone, cefotaxime, cefoxitin, cefsulodin and ceftazidime were inhibited by aztreonam 50% by 6.3 micrograms ml-1 and 90% by 16 micrograms ml-1. Aztreonam was as active as ceftazidime against Serratia marcescens, all strains were inhibited by 3.1 micrograms ml-1 and 90% by 1.6 micrograms ml-1. There was no major difference between MBC and MIC values of aztreonam and the effect of inoculum size upon MIC values was observed at 10(7) CFU.