高效液相色谱法测定微量耳血中头孢他定的浓度

本文介绍采取微量耳血以高效液相色谱法测定头孢他定（Ｃｅｆｔａｚｉｄｉｍｅ）的血药浓度。血样经６％高氯酸沉淀蛋白，流动相为含２５％甲醇的０．０５ｍｏｌ／Ｌ醋酸铵溶液，以冰醋酸调节ｐＨ值至４～５，检测波长为２５４ｎｍ，内标物为头孢唑啉（Ｃｅｆａｚｏｌｉｎ）。经对家兔采取微量耳血测定其血药浓度，可知头孢他定为二室模型，Ｔ＿１／２α为０．１８±０．０５ｈ，Ｔ＿１／２β为１．７５±０．０７ｈ。并对３名住院病人静脉注射１ｇ头孢他定后定时分别取微量耳血进行分析，所得结果与文献基本一致。本文方法简便、快速，结果令人满意。     

生长抑素和头孢噻甲羧肟对急性出血坏死性胰腺炎早期细菌移位的影响

为探讨急性出血坏死性胰腺炎（ＡＨＮＰ） 感染的防治, 我们观察了头孢噻甲羧肟和生长抑素对ＡＨＮＰ早期细菌移位的影响。结果提示生长抑素具有肠粘膜屏障保护作用, 可能与其清除肠道氧自由基有关。我们还发现ＡＨＮＰ早期应用抗生素可减轻血行的细菌移位。     

头孢吡肟治疗围术期医院获得性肺炎

目的　观察头孢吡肟治疗骨科围术期医院获得性肺炎的疗效及安全性 ,并与头孢他啶进行比较。方法　骨科围术期医院获得性肺炎 70例随机分为两组 :头孢吡肟组 3 5例 ,静滴 1.0～ 2 .0g ,2次 /d ;头孢他啶组 3 5例 ,静滴 1.0～ 2 .0g ,2次 /d ;两组均治疗 1～ 2周。结果　头孢吡肟组及头孢他啶组临床有效率分别为 94.2 9%及 91.43 % (P >0 .0 5 ) ,细菌清除率分别为 94.12 %及 90 .91% (P >0 .0 5 ) ,不良反应发生率均为 2 .86% (P >0 .0 5 )。结论　头孢吡肟治疗骨科围术期医院获得性肺炎的疗效显著而又安全     

头孢他啶中间体7β位三苯甲基侧链酸的合成

目的 研究头孢他啶7β位三苯甲基侧链酸(Z)-2-[(1-叔丁氧基羰基-1-甲乙氧)亚氨基]-2-(2-三苯甲氨基噻唑-4-基)乙酸的合成路线。方法 以(Z)-2-酮肟-2-(2-氨基噻唑-4-基)乙酸乙酯为原料，经过氨基保护、醚化、选择性水解等反应，合成头孢他啶7口位三苯甲基侧链酸(Z)-2-[(1-叔丁氧基羰基-1-甲乙氧)亚氨基]-2-(2-三苯甲氨基噻唑-4-基)乙酸。结果和结论 合成了头孢他啶7口位三苯甲基侧链酸(Z)-2-[(1-叔丁氧基羰基-1-甲乙氧)亚氨基]-2-(2-三苯甲氨基噻唑-4-基)乙酸，核磁共振氢谱确证了目标化合物及各个中间体的结构。     

RP-HPLC法同时测定注射用粉末中他唑巴坦和头孢他啶组分的含量

目的建立反相高效液相色谱法用于同时测定他唑巴坦和头孢他啶的含量.方法采用Zorbax 300SB-C18色谱柱, 流动相为甲醇-磷酸盐缓冲液 (pH=5.6),检测波长为220 nm.结果他唑巴坦和头孢他啶分别在0.62-631.8 μg·mL-1和 0.66-677.5 μg·mL-1内呈线性关系,平均加样回收率分别为98.8% - 101.4%和99.1%-100.2%,日内和日间精密度分别为0.2%-1.5%和0.1%-2.6%.结论该法简单、精确、快速、重复性好,可以满足其原料和制剂的质量控制要求.     

A Comparative Study on Aztreonam,Ceftazidime and Amikacin in the Treatment of Complicated Urinary Tract Infections

Summary

In a prospective, randomized trial, aztreonam (1 g intravenously or intramuscularly, twice daily) was compared with ceftazidime (1 g intravenously or intramuscularly, twice daily) and amikacin (500 mg intravenously or intramuscularly, twice daily) in 76 patients aged 24 to 84 years (mean, 59.7 years) with complicated urinary tract infections. Initial pathogens included Escherichia coli (47.5%), Pseudomonas aeruginosa (22.5%), Klebsiella spp. (9%), Proteus spp. (7.5%) and Enterobacter spp (6%). In four patients initial urine cultures yielded more than one organism. All pathogens were sensitive to the three study drugs. Including performance of 4- to 6-week follow-up cultures, eradication of the pathogens occurred in 72% of patients treated with aztreonam, in 74% of those treated with ceftazidime and in 71% treated with amikacin (p>0.05). Clinical success was observed in 84% of patients treated with aztreonam, in 82% of those treated with ceftazidime and in 85% treated with amikacin (p>0.05). All drugs were well tolerated. It is concluded that aztreonam, ceftazidime and amikacin are equally effective and safe for the treatment of complicated urinary tract infections due to susceptible organisms.     

Meta-analysis: combination of meropenem vs ceftazidime and amikacin for empirical treatment of cancer patients with febrile neutropenia

Background:Meropenem monotherapy vs ceftazidime plus amikacin have been approved for use against febrile neutropenia. To assess the effectiveness and safety of them for empirical treatment of cancer patients with febrile neutropenia, we conducted a meta-analysis of randomized controlled trial.Methods:Randomized controlled trials on ceftazidime plus amikacin, or/and monotherapy with meropenem for the treatment of cancer patients with febrile neutropenia were identified by searching Cochrane Library, PubMed, Science Direct, Wiley Online, Science Citation Index, Google (scholar), National Center for Biotechnology Information, and China National Knowledge Infrastructure. Data on interventions, participants’ characteristics and the outcomes of therapy, were extracted for statistical analysis. Seven trials fulfilled the inclusion criteria.Result:The treatment with ceftazidime plus amikacin was more effective than meropenem (OR = 1.17; 95% CI 0.93–1.46; 1270 participants). However, the treatment effects of the 2 therapy methods were almost parallel in adults (OR = 1.15; 95% CI 0.91–1.46; 1130 participants older than 16). Drug-related adverse effects afflicted more patients treated with ceftazidime plus amikacin (OR = 0.78; 95% CI 0.52–1.15; 1445 participants). The common responses were nausea, diarrhea, rash, and increased in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and bilirubin.Conclusion:Ceftazidime plus amikacin should be the first choice for empirical treatment of cancer patients with febrile neutropenia, and meropenem may be chosen as a last defense against pathogenic bacteria.     

Novel β-lactam/β-lactamase inhibitors versus alternative antibiotics for the treatment of complicated intra-abdominal infection and complicated urinary tract infection: a meta-analysis of randomized controlled trials

Introduction: The aim of this study is to compare the efficacy and safety of novelBL/BLIs with alternative antibiotics for the treatment of cIAI and cUTI.

Area covered: We performed a systematic review and meta-analysis of all randomized controlled trials comparing novel BL/BLIs with other antibiotics for the treatment of cIAI and cUTI. The primary outcome included clinical and microbiological treatment success.

Expert commentary: We found that novel BL/BLIs obtained a similar clinical outcome with other antibiotics in CE population (OR = 1.07, 95%CI = (0.80, 1.44), P = 0.64). However, novel BL/BLIs had better clinical treatment success in the cUTI subgroup (OR = 2.14, 95%CI = (1.06, 4.31), P = 0.03). Furthermore, novel BL/BLIs achieved significant microbiological treatment success in patie nts with cUTI (OR = 1.70, 95%CI = (1.29, 2.25), P = 0.0002) and had higher eradication rates for Gram-negative pathogens (OR = 1.82, 95%CI = (1.26, 2.64), P = 0.001) including E.coli and K.pneumoniae. No difference was observed concerning the incidence of mortality and adverse events between the two groups. Therefore, we concluded that novel BL/BLIs are not inferior to other available antibiotics for the treatment of cIAI, and they have advantages in patients with cUTI. Simultaneously, they are sensitive to Gram-negative pathogens, especially for E.coli and K.pneumoniae.     

头孢他啶与头孢吡肟治疗药物监测的高效液相色谱方法探索及其临床采样流程建立

目的： 建立同时测定头孢他啶和头孢吡肟血药浓度的高效液相色谱（high performance liquid chromatography,HPLC）法及其临床采样流程,并应用于临床治疗药物监测。方法： 采用CAPCELL PAK C₁₈（4.6 mm×250 mm,5.0 μm）色谱柱进行色谱分离,流动相A为50 mmol·L^-1磷酸二氢钾溶液,流动相B为混合有机相（乙腈：甲醇：水=7：2：1）,A：B（V/V,93：7）,流速1.0 mL·min^-1,波长为254 nm,盐酸雷尼替丁为内标,以ACP-1去蛋白剂沉淀蛋白,旋涡离心后进样30 μL分析,同时考察全血中两药在不同抗凝管、不同温度下放置不同时间的稳定性。结果： 头孢他啶和头孢吡肟的血浆质量浓度线性范围分别是0.57~267.34 μg·mL^-1、0.54~208.49 μg·mL^-1,低、中、高质控样品的日内、日间精密度均小于15%,萃取回收率分别为90.9%~95.4%、88.6%~97.7%;全血稳定性试验中,以EDTA-K2管采血的头孢他啶与头孢吡肟血浆在6℃及24℃下均能稳定48 h,37℃下稳定10 h;而以肝素钠管采血的头孢他啶和头孢吡肟血浆在6℃及24℃下能稳定24 h,37℃下能稳定4 h。结论： 所建立的方法具有灵敏度高、稳定性好、操作简便等优点,并根据全血稳定性结果建立了一套临床采样流程,为头孢他啶和头孢吡肟的TDM标准化与规范化建设提供参考依据。     

Population Pharmacokinetics and Dosing Simulations of Ceftazidime in Chinese Neonates

An accurate dosage determination is required in neonates when antibiotics are used. The adult data cannot be simply extrapolated to the pediatric population due to significant individual differences. We aimed to identify factors impacting ceftazidime exposure in neonates and to provide drug dosing guidance to clinicians. Forty-three neonates aged less than 60 days with proven or suspected infections were enrolled in this study. After intravenous administration, blood samples were collected, and plasma ceftazidime concentration was determined using a HPLC method. Pharmacokinetic data were fitted using a nonlinear mixed-effects model approach. One-compartmental model could nicely characterize the ceftazidime in vivo behavior. The covariate test found that the postmenstrual age (day) was strongly associated with systemic drug clearance (L/h), and the effect of body weight (kg) was identified as the covariate on distribution volume (L). Compared with the base model, the addition of covariates improved the goodness-of-fit of the final model. Model validation (bootstrap, visual predictive check, and prediction-corrected visual predictive check) suggested a robust and reliable pharmacokinetic model was developed. Personalized dosage regimens were provided based on model simulations. The intravenous dose should be adjusted according to postmenstrual age, body weight, and minimum inhibitory concentration.