半合成及合成青霉素皮试液的简易配制方法

半合成及合成青霉素有：苯唑西林钠、氯唑西林钠、氟氯西林、氨苄西林、阿莫西林、哌拉西林钠、替卡西林、美洛西林钠、阿洛西林钠、氨苄西林钠-舒巴坦钠、替卡西林钠-克拉维酸钾、阿莫丙林钠-克拉维酸钾、哌拉西林钠-他唑巴坦钠等.按《新编药物学》（2007年1月第16版）要求：青霉素类不同品种间存在着交叉过敏关系,青霉素类药物在应用前可用青霉素G钠皮试液进行皮试,     

叶酸-巯基衍生物的制备

目的：在叶酸的γ羧基上引入活性的巯基，从而更有利于制得叶酸复合物。方法：通过叶酸与半胱氨酸之间酰胺化反应，并经制备液相纯化的叶酸-γ-半胱氨酸结果：制得的叶酸-γ-半胱氨酸纯度高，收率为18％。     

临床常用β-内酰胺类抗菌药物对果糖胺检测的干扰分析

目的：观察临床常用的13种β‐内酰胺类抗菌药物对果糖胺检测项目的干扰情况。方法将抗菌药物用注射用水配制成系列溶液,按5％体积加入到新鲜的混合血清中,评价不同抗菌药物对果糖胺检测结果的干扰。结果头孢硫脒和替卡西林钠/克拉维酸钾的血药浓度分别达到37．5mg/L和247．5μg/mL时,开始对果糖胺的检测产生正干扰,但干扰程度与果糖胺血清浓度无关。结论头孢硫脒和替卡西林钠/克拉维酸钾对果糖胺检测结果存在干扰。     

临床常用β-内酰胺类抗生素对血清果糖胺检测的干扰分析

目的 评价临床常用β-内酰胺类抗生素对NBT法检测果糖胺的干扰效应.方法 遵循CLSI EP7-A2文件,将临床常用13种β-内酰胺类抗生素配制成最高浓度为20倍血药峰浓度的系列溶液,按照5％体积加入到新鲜混合血清中,检测新鲜混合血清果糖胺的结果,分析干扰效应.结果 替卡西林钠/克拉维酸、头孢硫脒对果糖胺检测存在正干扰,替卡西林钠/克拉维酸75％血药峰浓度、头孢硫脒50％血药峰浓度开始干扰造成果糖胺检测结果超出x＋1.96s范围,且干扰值与干扰药物浓度呈正相关,其它11种β-内酰胺类抗生素对果糖胺检测没有干扰.结论 替卡西林钠/克拉维酸、头孢硫脒对NBT法检测果糖胺存在正干扰,临床应在用药前或静脉滴注1～2个半衰期后采样检测果糖胺以避免干扰.     

泊马度胺的合成工艺改进

目的改进免疫调节剂泊马度胺的合成方法。方法以3-硝基邻苯二甲酸为原料,制得中间体3-氨基邻苯二甲酸;以N-Boc-L-谷氨酰胺为原料,制得3-氨基-2,6-哌啶二酮盐酸盐,这两个中间体经一步缩合反应即得到目标产物泊马度胺。结果与结论反应总收率为53.21%(以3-硝基邻苯二甲酸计),纯度为99.4%(HPLC法),此合成方法具有反应步骤少、操作简单、后处理方便、无废水污染且无重金属残留等优点。     

替米沙坦的合成

目的：合成替米沙坦并对其工艺进行改进。方法：以3-甲基-4-硝基苯甲酸为起始原料，合成制备替米沙坦。结果：该合成路线工艺总收率36．3％。结论：此合成路线工艺产率高，步骤少，适合于替米沙坦的生产。     

3,5—二氯邻羟基苯磺酸钠的合成及其临床应用

目的制备３，５－二氯邻羟基苯磺酸钠（ＤＣＨＢＳ）以取代Ｔｒｉｎｄｅｒ‘ｓ反应中所用的苯酚及四氯酚。方法２，４－二氯苯酚和浓硫酸在１００℃进行磺化反应，制得ＤＣＨＢＳ；将其和氧化物化酶、尿酸酶、４－氨基氨替比林等组成尿酸检测试液，进行灵敏度、精确度、回收率、干扰试验、稳定怀考查，并与 四氯酚法及与进口试剂比，作相关试验，结果ＤＣＨＢＳ使用浓度为６．０ｍｍｏｌ／Ｌ，检测波长为５１０ｎｍ，尿酸浓度在２４     

替米沙坦分散片的制备工艺研究

目的：采用L9（3^4）正交试验设计研究替米沙坦分散片的制备工艺，优选最佳工艺条件。方法：采用粉末直接压片法优选工艺条件，并以崩解时限、硬度作为考核指标。结果：最佳制各工艺是：微晶纤维素（102型）25％，PVPP5％，喷雾干燥乳糖20％，微粉硅胶2%，粉末直接压片。结论：替米沙坦分散片的制备工艺合理。     

下呼吸道标本铜绿假单胞菌的耐药性研究

目的 :了解下呼吸道标本铜绿假单胞菌 (PA)的耐药情况 ,比较重症监护病房 (ICU)与普通病房 (GW )下呼吸道标本PA的耐药性 ,为临床合理应用抗生素提供依据。方法 :总结 1996年 1月～ 2 0 0 0年 12月期间从临床下呼吸道标本中分离的12 80株PA(其中ICU6 5 5株 ,GW 6 2 5株 )的药敏试验资料 ,统计分析PA的耐药情况。结果 :对 12种抗生素的耐药性监测发现 ,PA对头孢他啶、亚胺培南、替卡西林钠 /克拉维酸钾、头孢哌酮、哌拉西林、环丙沙星、庆大霉素及阿米卡星的耐药率分别为 2 2 .8%、16 .5 %、9.1%、13.4 %、5 .9%、16 .9%、16 .6 %和 3.0 % ,对其他各抗生素耐药率均很高 ,部分在 90 %以上。ICU中PA对头孢他啶、亚胺培南、替卡西林钠 /克拉维酸钾、环丙沙星、庆大霉素的耐药率在明显高于GW中的PA(P <0 .0 5 )。结论 :PA下呼吸道感染的耐药率高 ,尤其在ICU中 ,大多呈多重耐药 ,应引起临床医师的高度重视     

医院获得性嗜麦芽窄食单胞菌下呼吸道感染或定植临床分析

目的探讨医院获得性嗜麦芽窄食单胞菌感染或定植的临床特点及药敏情况。方法回顾性的分析2010年1月至2015年12月期间102例标本培养嗜麦芽窄食单胞菌阳性病历临床和检验资料。结果嗜麦芽窄食单胞菌培养阳性病例下呼吸道标本占94.1%,其中定植菌占70.5%;ICU病例占80.3%;有侵袭性操作史占96.0%;使用过广谱抗菌药物占100%,其中碳青霉烯类药物病例占59.8%。嗜麦芽窄食单胞菌对多种抗菌药物耐药,庆大霉素、妥布霉素、丁胺卡钠、头胞吡肟、头胞他啶、头胞曲松、亚胺培南西司他丁钠、氨曲南、氧哌嗪青霉素耐药率分别为91.2%、88.0%、79.4%、79.5%、54.5%、92.2%、99.0%、96.1%、73.0%;敏感药物为复方磺胺甲恶唑、替卡西林+克拉维酸钾,敏感率分别为83.3%、68.6%。结论嗜麦芽窄食单胞菌培养阳性病例以存在于下呼吸道的定植菌为多。有效治疗嗜麦芽窄食单胞菌药物为复方磺胺甲恶唑、替卡西林联用克拉维酸钾。     

Antibiotic prophylactic uterine lavage in cesarean section: a double-blind comparison of saline, ticarcillin, and cefoxitin irrigation in indigent patients

The purpose of this present study was to determine whether intraoperative antibiotic uterine irrigation was effective in reducing febrile morbidity (Part 1), and to determine whether ticarcillin disodium (Ticar) or cefoxitin sodium (Mefoxin) was the more effective solution (Part 2). The indications for cesarean section had an effect on febrile morbidity. In patients having nonelective cesarean section, febrile morbidity was high, occurring in 62.7% of the saline control group and 32.9% of those receiving ticarcillin disodium irrigation. In patients having elective cesarean section, febrile morbidity was lower (28% in the saline control group and 8.3% in the ticarcillin group [P less than or equal to .05]). Ticarcillin and cefoxitin were equal in reducing postoperative febrile morbidity. The use of prophylactic antibiotics, therefore, is indicated both in high-risk patients having nonelective cesarean section and in low-risk patients having elective repeat cesarean section.     

Stability of piperacillin and ticarcillin in AutoDose infusion system bags.

OBJECTIVE: To evaluate the physical and chemical stability of piperacillin sodium 3 and 4 g/100 mL and ticarcillin disodium 3 g/100 mL each admixed in NaCl 0.9% injection packaged in AutoDose Infusion System bags. DESIGN: Triplicate test samples of the penicillin antibiotics in NaCl 0.9% injection were packaged in ethylene vinyl acetate (EVA) plastic containers, AutoDose bags, designed for use in the AutoDose Infusion System. Samples were stored protected from light and evaluated at appropriate intervals for up to seven days at 23 degrees C and up to 30 days at 4 degrees C. Physical stability was assessed using turbidimetric and particulate measurement as well as visual inspection. Chemical stability was assessed by HPLC. RESULTS: All of the penicillin admixtures initially were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low initially and exhibited little change in the ticarcillin disodium samples throughout the study. The piperacillin sodium samples exhibited small increases in measured haze throughout the study, but no accompanying increase in particulates > or = 1.04 microm was found. All samples were essentially colorless throughout the study. HPLC analysis found some decomposition in the samples. Piperacillin sodium exhibited a 9-10% loss after five days at 23 degrees C. In the samples stored at 4 degrees C, piperacillin sodium exhibited acceptable stability through 21 days of storage, but losses exceeded 10% after 30 days. Ticarcillin disodium exhibited a 7% loss after three days, but 14% after five days at 23 degrees C. Less than 7% loss occurred after 21 days, but 12% loss after 30 days at 4 degrees C. CONCLUSIONS: Piperacillin sodium and ticarcillin disodium exhibited physical and chemical stability consistent with previous studies on these drugs. The AutoDose Infusion System bags were not found to adversely affect the physical and chemical stability of these penicillin antibiotics.     

Clinical and Pharmacological Studies of Ticarcillin in Gram-Negative Infections

Twenty-seven patients with serious gram-negative infections were treated with ticarcillin in an average daily dosage of 237 mg/kg (range, 174 to 307 mg/kg). Ticarcillin was bactericidal for all infecting organisms in concentrations ranging from 31.2 to 125 μg/ml. Five of 8 patients (62%) with overwhelming Pseudomonas pneumonia were cured or improved, and 9 of 12 (75%) were cured of pneumonia caused by other gram-negative organisms. Of six extrapulmonary infections caused by Pseudomonas, five (83%) were cured or improved. In seven cases, the infecting organism reisolated during therapy was more resistant to ticarcillin than the primary isolate. The serum half-life of ticarcillin in three patients with renal failure was 11.2 ± 1.0 h, and during hemodialysis it decreased to 6.3 ± 1.8 h. There were two episodes of superinfection with resistant organisms. Thirteen patients (48%) manifested eosinophilia, one of whom had severe urticaria. Prolongation of bleeding time was attributable to ticarcillin in two patients. Ticarcillin appears to be effective for therapy of serious gram-negative infections in dosages 30 to 50% less than those recommended for carbenicillin.     

In vitro activity of carbenicillin, ticarcillin, sisomicin and netilmicin alone and in combination against Pseudomonas aeruginosa.

The in vitro activity of carbenicillin, ticarcillin, sisomicin and netilmicin alone and in combination against 35 strains of Pseudomonas aeruginosa was investigated. Ticarcillin was more active than carbenicillin and sisomicin was more active than netilmicin. There was enhanced killing of many strains of P. aeruginosa by the combination of carbenicillin or ticarcillin with sisomicin or netilmicin.     

HPLC法测定注射用氧化型谷胱甘肽二钠有关物质及含量

目的:考察不同色谱条件下注射用氧化型谷胱甘肽二钠有关物质的色谱行为,建立注射用氧化型谷胱甘肽二钠有关物质高效液相色谱分析方法及含量测定方法。方法:固定相为ZorbaxXB-C18(4.6mm×250mm,5μm);流动相为0.006M辛烷磺酸钠溶液-甲醇(95:5);检测波长为210nm,柱温30℃。结果:注射用氧化型谷胱甘肽二钠的线性范围为0.5-10μg,r=0.9999,总有关物质含量小于1%。结论:此法简单,分离度良好,结果准确,可以用于注射用氧化型谷胱甘肽二钠的含量测定和有关物质的检测。     

In vitro susceptibility of Stenotrophomonas maltophilia to various antimicrobial combinations.

Stenotrophomonas maltophilia has emerged as a significant pathogen in compromised patients, causing infections which are difficult to treat. Clinical isolates from patients in the Tucson area were tested against single and combination antibiotics using three testing methods. Ticarcillin/clavulanate, trimethoprim/sulfamethoxazole and trovafloxacin provided comparable inhibitory activity, in vitro. Ciprofloxacin, imipenem and ticarcillin were active less often. Agreements between disk diffusion and broth microdilution results were poor for ciprofloxacin and trimethoprim/sulfamethoxazole; however, agreement was > or = 90% for the other drugs tested. Major or very major errors were observed with ticarcillin, ticarcillin/clavulanate, and trovafloxacin. The addition of aztreonam to ticarcillin/clavulanate enhanced the activity compared to ticarcillin/clavulanate alone using the double-disk diffusion, broth microdilution (checkerboard), and time-kill testing methods. Trovafloxacin exhibited good activity by all three methods, with bactericidal activity at > or = 2x MIC. These results indicate that the newer fluoroquinolones or the triple combination of ticarcillin/clavulanate plus aztreonam may be potential options for treatment of infection caused by S. maltophilia in patients who are intolerant to or fail trimethoprim/sulfamethoxazole therapy.     

Ticarcillin Therapy of Infections

Ticarcillin was administered as initial therapy during 73 episodes of infections occurring in 69 adults with neoplastic diseases. During the first six infections, doses of 5 gm were dissolved in 200 ml of solvent and administered intravenously over a 2-h period every 6 h. Four of six infections responded to therapy. However, two of the five Pseudomonas infections failed to respond, whereas the organisms causing the infection were sensitive to ticarcillin in vitro. During the remaining 67 infections, doses of 3.5 g were similarly dissolved and administered intravenously over a 2-h period every 4 h. The overall response to ticarcillin in these 67 infections was 43%. However, 18 of 20 Pseudomonas infections, three Proteus spp. infections, and one infection caused by H. influenzae responded. Only 1 of 7 infections caused by mixed organisms and 5 of 13 infections in which the etiologic agent could not be identified responded. Ticarcillin was ineffective against the majority of Escherichia coli and Klebsiella spp. infections, organisms which were resistant to ticarcillin in vitro. The majority of patients were neutropenic, but the response rate was not dependent on the number of circulating polymorphonuclear neutrophilic leukocytes. Superinfection occurred in seven patients. Erythematous skin rash occurred in two patients, which subsided after discontinuation of the drug. No liver or renal toxicity occurred that could be attributed to ticarcillin.     

Effect of Time and Concentration Upon Interaction Between Gentamicin, Tobramycin, Netilmicin, or Amikacin and Carbenicillin or Ticarcillin

An aminoglycoside antibiotic and carbenicillin or ticarcillin are widely used in the treatment of patients with gram-negative bacillus infections. This study evaluated the effect of time upon in vitro interaction between mixtures of four aminoglycosides at two concentrations with carbenicillin or ticarcillin at four concentrations. By linear regression analysis, the inactivation of each aminoglycoside was shown to be directly proportional to the concentration of carbenicillin (P < 0.001). Inactivation was significantly (P < 0.01) greater for gentamicin and tobramycin than for amikacin or netilmicin at all carbenicillin concentrations. At carbenicillin concentrations of 300 and 600 mug/ml, significantly (P < 0.005) less inactivation of amikacin occurred when compared to netilmicin. Ticarcillin produced a significant (P < 0.025) inactivation of gentamicin and tobramycin, with inactivation being directly proportional to ticarcillin concentration. No inactivation of amikacin or netilmicin activity occurred unless the ticarcillin concentration was 600 mug/ml. No significant change in aminoglycoside activity occurred when stored with ticarcillin or carbenicillin at concentrations ranging from 100 to 600 mug/ml at -70 degrees C for 56 days. When an aminoglycoside and carbenicillin or ticarcillin are indicated in patients with renal failure, this study supports the use of ticarcillin with either amikacin or netilmicin.     

Combined Activity of Clavulanic Acid and Ticarcillin Against Ticarcillin-Resistant, Gram-Negative Bacilli

Fifty-one clinical isolates of ticarcillin-resistant, gram-negative bacilli were tested for susceptibility to combinations of ticarcillin and clavulanic acid (BRL 14151), a potent beta-lactamase inhibitor. Minimal inhibitory concentrations (MICs) were measured by a microdilution method, and minimal bactericidal concentrations for selected strains were measured by the broth dilution method. Ticarcillin MICs were >/=128 mug/ml for all and >/=512 mug/ml for 38 (75%) of the strains. Thirty-nine strains of Enterobacteriaceae tested included Escherichia coli (14), Klebsiella pneumoniae (16), Citrobacter sp. (3), Enterobacter sp. (3), Salmonella enteritidis (1), Serratia marcescens (1), and Proteus mirabilis (1). Ticarcillin MICs for 34 strains (88%) were lowered at least threefold by the addition of 1.0 mug of clavulanic acid per ml. Against 33 strains (85%), the MICs were 64 mug or less per ml in the presence of 5 mug of clavulanic acid per ml. In contrast, the MICs for seven of eight strains of Pseudomonas aeruginosa were unaffected by the addition of up to 10 mug of clavulanic acid per ml. Ticarcillin with 5 mug of clavulanic acid per ml was bactericidal against ticarcillin-resistant (MIC >/= 2,048 mug/ml) E. coli, K. pneumoniae, Enterobacter, and P. mirabilis.     

Discrepancies between disk diffusion and broth susceptibility studies of the activity of ticarcillin plus clavulanic acid against ticarcillin-resistant Pseudomonas aeruginosa.

Ticarcillin and clavulanic acid in combination were tested against 40 Pseudomonas aeruginosa isolates resistant to ticarcillin by disk diffusion. A total of 21 isolates (53%) were susceptible to ticarcillin-clavulanate by disk diffusion, under currently recommended criteria for ticarcillin susceptibility. Macro-broth dilution tests (ticarcillin plus clavulanic acid, 2 micrograms/ml) confirmed susceptibility (MIC less than or equal to 64 micrograms/ml) of only 8 (38%) of 21 isolates. Time-kill studies of disk diffusion susceptible isolates indicated 2 log10 or greater killing of most isolates at 6 h in broth containing ticarcillin (64 micrograms/ml) combined with clavulanic acid (1, 2, 5, or 10 micrograms/ml). After 6 h, regrowth was common in all concentrations of clavulanic acid except 10 micrograms/ml. Regrowth populations were resistant to ticarcillin-clavulanate by MIC determination. Poor bactericidal activity of ticarcillin-clavulanate against ticarcillin-resistant P. aeruginosa was confirmed, as most isolates did not undergo 99.9% or greater killing at 24 h in all concentrations of clavulanic acid. Serotype O-11 was our most common serotype and was associated with disk diffusion "pseudosusceptibility." Concomitant disk diffusion testing of ticarcillin-clavulanate and ticarcillin is recommended for testing the susceptibility of P. aeruginosa to ticarcillin-clavulanate by disk diffusion. P. aeruginosa isolates resistant to ticarcillin should as a rule be considered also resistant to ticarcillin-clavulanate, despite apparent susceptibility by disk diffusion.