双黄连口服液联合庆大霉素的体外抗菌作用研究

目的研究双黄连口服液和庆大霉素联用对金黄色葡萄球菌、铜绿假单胞菌的体外抗菌作用。方法采用微量溶液稀释法,测定双黄连口服液和庆大霉素分别对金黄色葡萄球菌、铜绿假单胞菌的最低抑菌浓度(MIC);采用棋盘联合药敏试验法,测定双黄连口服液和庆大霉素联用分别对金黄色葡萄球菌、铜绿假单胞菌的部分抑菌浓度(FIC)指数。结果双黄连口服液对金黄色葡萄球菌和铜绿假单胞菌的MIC分别是46.88 mg.mL-1(稀释度1∶32)和375 mg.mL-1(稀释度为1∶4);庆大霉素对金黄色葡萄球菌和铜绿假单胞菌的MIC分别是0.25和1 U.mL-1;双黄连口服液和庆大霉素联用对金黄色葡萄球菌和铜绿假单胞菌的FIC指数均是0.56。结论双黄连口服液联用庆大霉素对金黄色葡萄球菌和铜绿假单胞菌药敏结果均呈相加作用。     

安息香提取物（XCQ）联合庆大霉素对铜绿假单胞菌的抗菌增效作用研究

目的：考察安息香提取物XCQ联合庆大霉素体内、外抗铜绿假单胞菌的抗菌增效作用。方法：采用体外药物敏感性实验筛选铜绿假单胞菌临床株的多重耐药性菌株,并测定庆大霉素、左氧氟沙星和XCQ对铜绿假单胞菌临床株的最小抑菌浓度（minimum inhibitory concentration,MIC）;采用牛津管法评价不同剂量XCQ联合庆大霉素的体外抗菌活性差异;通过小鼠尾静脉注射铜绿假单胞菌菌液构建小鼠细菌感染性疾病动物模型,造模前3h灌胃XCQ溶液和造模后立即灌胃给予庆大霉素溶液,统计5 d内感染小鼠的生存率。结果：筛选出一株铜绿假单胞菌多重耐药菌株,该菌株对庆大霉素的MIC值为1μg﹒mL-1;XCQ在体外能提高庆大霉素的抗菌活性,并存在量效关系;XCQ在体内能提高庆大霉素对感染小鼠的保护性,提高模型动物存活率。结论：安息香提取物XCQ在体内、外均能提高庆大霉素对抗铜绿假单胞菌的抗菌作用。     

金银花水煎液抗绿脓杆菌生物膜作用及其与庆大霉素的协同作用

目的观察金银花水煎液体外抗铜绿假单胞菌生物膜的作用及与庆大霉素的协同作用。方法通过试管稀释法测定金银花水煎液和庆大霉素对铜绿假单胞菌的最小抑菌浓度(MIC),用MTT法建立体外铜绿假单胞菌生物膜并检定金银花水煎液和庆大霉素不同MIC浓度的抗铜绿假单胞菌生物膜的作用。结果金银花水煎液对绿脓杆菌的MIC为125g.L-1,SMIC也为125 g.L-1;庆大霉素对绿脓杆菌的MIC为1.56 mg.L-1,SMIC为25 mg.L-1,与金银花的协同作用对绿脓杆菌的SMIC为1.56 mg.L-1。结论金银花水煎液在体外能抑制铜绿假单胞菌对固体表面的黏附能力及生物膜形成能力,并能破坏铜绿假单胞菌已形成的生物膜,增强庆大霉素对生物膜内铜绿假单胞菌的清除作用。     

复方庆大霉素普鲁卡因口服液的微生物限度检查法

目的建立复方庆大霉素普鲁卡因口服液的微生物限度检查法。方法通过加菌回收的方法对不同医院生产的复方庆大霉素普鲁卡因口服液进行验证。对照菌株为大肠埃希菌［CMCC(B)44102］，沙门菌［CMCC(B)50094］，金黄色葡萄球菌［CMCC(B)26003］和白念珠菌［CMCC(F)98001］。结果被检复方庆大霉素普鲁卡因口服液的霉菌、酵母菌及控制菌回收试验均达到要求。结论复方庆大霉素普鲁卡因口服液中的霉菌、酵母菌可采用常规计数法检查，控制菌可采用薄膜过滤法进行检查.     

庆大霉素及其组份的分离测定方法

庆大霉素是由一些小单孢菌产生的一族多组份的氨基糖甙类抗生素,抗菌谱广,已广泛用于临床,对绿脓杆菌、肠道杆菌和金葡球菌等感染的疾病疗效显著。国外对庆大霉素进行了广泛的研究,到目前为止已发现的组份有几十种。由于庆大霉素产生菌在生物合成过程中,通过     

庆大霉素动态耐药高产菌种的选育方法

用庆大霉素炭脱液动态处理庆大霉素棘孢小单孢菌，使庆大霉素菌种平均发酵单位提高３００U/ml，可以直接制备庆大霉素高产菌种。对提高抗生素的发酵水平有显著效果。     

乙基西索米星对临床分离耐药菌体外抗菌作用研究

本文研究比较了乙基西索米星及其他四种氨基糖苷类抗生素对临床分离２１９株庆大霉素耐药菌和６５株β－内酰胺类多重耐药菌的体外抗菌作用。研究结果表明，乙基西索米星对耐庆大霉素与耐β－内酰胺类的耐药金葡萄菌均有强大抗菌活性，ＭＩＣ５０与ＭＩＣ９０分别为４与８ｍ／Ｌ作用与丁胺卡那霉素相似，优于妥布霉素。乙基西索米星对耐庆大霉素与耐β－内酰胺类的肠杆菌科阴性杆菌半数以上仍有抗菌作用，其中耐β－内酰胺类的绿脓假单胞菌与不动杆菌对乙基西索来星仍高度敏感。ＭＩＣ９０分别为４与２ｍｇ／Ｌ，耐β－内酰胺类的肺炎克雷伯氏菌对乙基西索米星也不敏感。对庆大霉素高度耐药的绿脓假单胞菌对乙基西索米星、妥布霉素也耐药。对耐庆大霉素与耐β－内酰胺类多数耐药菌有效的三种氨基糖昔类抗生素中以丁胺卡那霉素作用最强，乙基西索来星次之，妥布霉素对耐药菌的作用与乙基西索米星相近，但对部分耐药菌的作用不及乙基西索米星。     

培养基及膜通透性对庆大霉素分泌的影响

研究了pH、葡萄糖与淀粉比值、微量元素、磷酸镁、表面活性剂对庆大霉素分泌的影响。对小单胞菌膜通透性的影响表明,庆大霉素产生菌质膜通透性的改善能促进庆大霉素的合成和分泌。     

不同能量重离子对庆大霉素生产菌绛红小单孢菌诱变的研究

采用重离子辐照技术，对庆大霉素产生菌绛红小单孢菌进行了诱变处理，本文报告诱变处理后筛选的部分结果。１材料和方法１．１菌种庆大霉素生产菌绛红小单孢菌，由兰州制药厂提供。生物检定菌为短小芽孢杆菌６３２０２。１．２培养基斜面培养基：可溶性淀粉１％；ＣａＣＯ...     

乙基西索米星与庆大霉素、妥布拉霉素和丁胺卡那霉素体外抗菌活性的比较

本文报道乙基西索米星对548株临床分离菌的体外抗菌作用,并与庆大霉素、妥布拉霉素和丁胺卡那霉素进行比较。丁胺卡那霉素对革蓝氏阴性杆菌的作用最强。乙基西索米星对金葡菌和其他革蓝氏阳性球菌(除肠球菌外)具良好抗菌作用,为四种氨基糖苷类抗生素中作用最强者。乙基西索米星对肠杆菌科细菌的作用与妥布拉霉素相似,但较庆大霉素强,为四者之中对绿脓杆菌的作用最差者。对庆大霉素、妥布拉和丁胺卡那霉素耐药的金葡菌中仍有40～86％的菌株对本品敏感,对庆大霉素和妥布拉霉素耐药的革蓝氏阴性杆菌中仍有30～46.8％的菌株对本品敏感。 鉴于临床致病菌对庆大霉素的耐药率逐渐增加,乙基西索米星对于国内临床上耐药革蓝氏阴性杆菌的作用及其机理值得进一步研究。     

庆大霉素的LC-MS分析

目的建立庆大霉素的LC-MS分析方法,对庆大霉素各组分进行定性和定量分析。方法利用宽pH范围XTerraLC-18(2.1mm×150mm,3μm)色谱柱,在碱性条件下,以乙腈-水(含0.2%氨水)为流动相,直接分离各组分;并采用LC-ESI-MS检测庆大霉素中各组分。结果用建立新方法,基线分离了庆大霉素中的4个主要组分和2个其他组分,并测定了4个主要组分的相对含量。结论新建立的LC-MS方法可用于该品种的定性及定量分析,该方法为庆大霉素质量控制和稳定性研究提供了可靠的分析手段。     

Nephrotoxicity: a comparison in humans of gentamicin and gentamicin C1 administration

The relative nephrotoxicities of the gentamicin complex (Garamycin) and gentamicin C₁ were studied using “acute” (intravenous infusion, five normal renal function subjects) and 3-day (multiple injections for 3 days, five normal renal function subjects) administration of the drug. Inulin, creatinine, and para-aminohippurate (PAH) clearances, renal concentrating capacity, urinary alkaline phosphatase, N-acetyl-β-d-glucosaminidase and β-glucuronidase enzyme excretions, and quantitative urinary sediment counts were measured before and during treatment. Although transient elevations of urinary enzymes occurred with both drugs, these were judged neither excessive nor abnormal. Renal function indicators showed no change after drug administration and there were no significant differences between drugs. Also, urinary sediment showed no changes from normal, and the gentamicin C₁ administration was not significantly different from results after gentamicin complex administration. By the presently rather imprecise criteria defining the lower limits of nephrotoxicity, neither drug when administered by the present recommendations for the upper dose limits for therapy with gentamicin complex was shown to be toxic. The 3-day multiple-dosing schemes for both drugs results in a total dose comparable to chronic dosing for 7–10 days at more usual doses and were judged to be comparable.     

Prescribing aids for gentamicin

1 A nomogram and a digital computer program have been developed to calculate dosage schedules of gentamicin for individual patients. The minimum input data consist of the patients' age, sex, body weight and serum creatinine concentration.

2 These prescribing aids have been evaluated in 36 patients with severe Gram negative infections. Renal function ranged from normal to complete anuria. Nomogram dosage schedules gave serum concentrations of gentamicin within the chosen therapeutic limits. Physician dosage schedules gave serum concentrations which sometimes exceeded and sometimes fell below these limits. The validity of the computer program was demonstrated by its ability to predict serum concentrations of gentamicin whatever the dosage schedule.

3 Half the patients recovered from the bacterial infection but seven remained infected and eleven died. Pseudomonas aeruginosa was the most difficult organism to eradicate.

4 Four of the patients who survived developed ataxia and two developed hearing loss at high frequencies. The risk of ototoxicity was a function of mean trough serum gentamicin concentration and duration of treatment. Ototoxicity was only detected in patients with serum creatinine concentrations above 3 mg/100 ml who tended to have higher trough concentrations. When treatment was prolonged beyond 8-10 days the risk of ototoxicity was increased without evidence of further substantial therapeutic benefit.

     

柱切换HPLC-ELSD法测定硫酸庆大霉素颗粒中庆大霉素C组分的研究

目的 建立柱切换高效液相色谱-蒸发光散射检测法(HPLC-ELSD)测定硫酸庆大霉素颗粒中庆大霉素C组分含量,并对2017年国家评价性抽验190批次样品进行检测。方法 采用配置切换六通阀的高效液相色谱仪,GRACE Apollo C18色谱柱( 250mm×4.6mm, 5μm),流动相为0.2mol/L三氟乙酸溶液:甲醇(96:4, V/V),柱温35℃,流速0.6mL/min,进样量25μL,ELSD漂移管温度110℃,载气流量2.5L/min,增益1。结果 采用新建的柱切换HPLC-ELSD法可有效去除辅料蔗糖等对测定的干扰,庆大霉素C组分(C1、C1a、C2、C2a)的平均回收率分别为98.9%、102.0%、100.1%和98.6%,RSD(n=9)分别为0.5%、0.4%、0.3%和0.6%,线性范围分别为0.0517~0.6465、0.0538~0.6729、0.0651~0.8136和0.0299~0.3738mg/mL。190批次样品中12批次样品的庆大霉素C1偏低,2批次样品的庆大霉素总C组分含量偏低,3批次样品的庆大霉素总C组分含量偏高。结论 新建方法准确简便,专属性良好,可为硫酸庆大霉素颗粒中庆大霉素C组分的控制提供参考。     

柱切换HPLC-ELSD法测定硫酸庆大霉素颗粒中庆大霉素C组分的研究

目的 建立柱切换高效液相色谱-蒸发光散射检测法(HPLC-ELSD)测定硫酸庆大霉素颗粒中庆大霉素C组分含量,并对2017年国家评价性抽验190批次样品进行检测。方法 采用配置切换六通阀的高效液相色谱仪,GRACE Apollo C18色谱柱( 250mm×4.6mm, 5μm),流动相为0.2mol/L三氟乙酸溶液:甲醇(96:4, V/V),柱温35℃,流速0.6mL/min,进样量25μL,ELSD漂移管温度110℃,载气流量2.5L/min,增益1。结果 采用新建的柱切换HPLC-ELSD法可有效去除辅料蔗糖等对测定的干扰,庆大霉素C组分(C1、C1a、C2、C2a)的平均回收率分别为98.9%、102.0%、100.1%和98.6%,RSD(n=9)分别为0.5%、0.4%、0.3%和0.6%,线性范围分别为0.0517~0.6465、0.0538~0.6729、0.0651~0.8136和0.0299~0.3738mg/mL。190批次样品中12批次样品的庆大霉素C1偏低,2批次样品的庆大霉素总C组分含量偏低,3批次样品的庆大霉素总C组分含量偏高。结论     

Monitoring serum levels of gentamicin to develop a new regimen for gentamicin dosage in newborns

The newborns studied had gestational ages ranging between 23-44 weeks, weights ranging between 725-4510 g, and were treated with standard doses of gentamicin (5.2 +/- 1.0 mg/kg/day). The gentamicin serum peak and trough levels were unrelated to administered doses, and a large proportion of patients had low (peak less than 4 micrograms/ml in 12%) or potentially toxic concentrations (trough greater than 2 micrograms/ml in 55%). The pharmacokinetic parameters (t1/2e, 8.2 +/- 4.8 h and Vd, 0.64 +/- 0.22 L/kg) varied markedly between patients. The newborn's weight, age, gestational age, and serum creatinine were factors of importance for the variability of gentamicin serum levels. The newborns were divided into four groups: gestational period less or more than 37 weeks and age below or above 7 days. These groups had different gentamicin serum levels and pharmacokinetic parameters. The results suggest that a gentamicin dosage regimen based on the division of newborn patients into subgroups or calculated from individual pharmacokinetic characteristics would decrease the risk of obtaining potentially toxic or subtherapeutic gentamicin concentrations after the use of standard doses.     

Population kinetics of gentamicin in neonates

A population kinetic analysis was carried out on sparse plasma gentamicin (GE) concentration data from 469 neonates obtained as part of a routine therapeutic drug monitoring (TDM) programme in the hospital neonatology unit.The best predictors of the kinetic parameters of the monoexponential model, volume of distribution (Vd) and clearance (CL), were the weight (WT) and gestational age (GA). Vd of the neonates was only related to WT, whereas the half-life was only related to the GA.     

WM88拮抗庆大霉素耳毒性实验观察

目的:初步了解WM88拮抗庆大霉素耳毒性的性能及其影响力.方法:设置庆大霉素组与庆大霉素加不同剂量WM88(10mg、20mg)的两组进行比较,观察听性脑干反应(ABR)阈值,眼震电图(ENG)的频率,了解其听功能及前庭功能的变化.仅结合耳蜗铺片琥珀酸脱氢酶(SDH)染色方法和扫描电镜观察耳蜗形态学变化.结果:听生理检查数据统计显示各组间无显著性差异;形态结果显示各组间无显著性差异.结论:本实验没有发现WM88对庆大霉素引起的耳蜗和前庭毒性有拮抗作用.