三种头孢类药物的输液稳定性影响因素研究

目的：研究头孢呋辛钠、头孢曲松钠、头孢噻肟钠在0．9％氯化钠注射液和5％葡萄糖注射液中的稳定性影响因素。方法：在不同的温度（8、25、37℃）、不同光照（光照强度2500 lx、避光）及不同时间（0、0．5、1、2、3h）条件下测定三种头孢类药物输液中药物的含量、pH值和不溶性微粒等。结果：在不同温度和光照条件下,三种药物与两种输液配伍后3h内含量基本稳定,头孢呋辛钠和头孢曲松钠在输液中的有关物质随着放置时间延长明显增加,头孢噻肟钠相对不明显。结论：三种头孢类药物与0．9％氯化钠和5％葡萄糖配伍在3h以内可以任意选择静滴时间,但最好即配即用,其中头孢呋辛钠和头孢曲松钠最好避光滴注;熟悉药物在输液中的稳定性影响因素有利于提高药物的临床疗效,促进合理用药。     

头孢曲松钠对大鼠局灶性脑缺血的神经保护作用及其机制

目的：探讨头孢曲松钠对局灶性脑缺血大鼠的神经保护作用及其机制。方法：将Sprague-Dawley（SD）大鼠随机分为头孢曲松钠预处理组、单纯缺血组和假手术组。头孢曲松钠预处理组于术前7 d腹腔注射头孢曲松钠200 mg?kg-1?d-1,然后制备大鼠局灶性脑缺血模型,缺血后3,6,12,24和48 h进行神经行为学评分,应用免疫组化法测定大鼠海马胶质细胞性谷氨酸转运体（glutamate transporter-1,GLT-1）水平。结果：局灶性脑缺血3 h后,脑组织GLT-1蛋白水平显著降低（P<0.01）,并且随着缺血时间的延长,GLT-1蛋白水平呈下降趋势,脑缺血后48 h降至最低（P<0.01）。与单纯缺血组比较,头孢曲松钠预处理组大鼠的神经行为学评分均显著降低（P<0.05）,海马GLT-1蛋白的表达显著增加（P<0.01）。结论：头孢曲松钠对局灶性脑缺血大鼠具有神经保护作用,其机制可能与增加GLT-1的表达、降低谷氨酸的兴奋性毒性作用有关。     

Bacterial meningitis: new therapeutic approaches

Bacterial meningitis remains a disease with high mortality and long-term morbidity. Outcome critically depends on the rapid initiation of effective antibiotic therapy. Since a further increase of the incidence of pathogens resistant to antibacterials can be expected both in community-acquired and nosocomial bacterial meningitis, the choice of an optimum initial empirical antibiotic regimen will gain significance. In this context, the use of antibiotics which are bactericidal but do not lyse bacteria, may emerge as a therapeutic option. Conversely, the role of corticosteroids, which decrease the entry of hydrophilic antibacterials into the cerebrospinal fluid, as adjunctive therapy will probably decline as a consequence of the increasing antibiotic resistance of bacteria causing meningitis. Consequent vaccination of all children at present is the most efficient manner to reduce disease burden.     

反渗透法制备注射用水的水质考察

本文应用微量稀释法研究了２４名施硬膜内手术患者应用头孢曲松、头孢噻肟和头孢呋肟后血清和脑脊液杀菌效价。结果表明，其中ＣＴＲＸ对肠杆菌科细菌的体内外抗菌活性最强，在脑脊液中的杀菌效价也较高，维持时间长，从而提示一日２次，每次１ｇ静脉给药，可望有效防治严重的肠杆菌科细菌所致颅脑手术后感染；ＣＴＸ对革兰工阳性球菌及肠杆菌科细菌的杀菌效价均较高，可用于防治颅脑混合细菌感染；ＣＦＲ在脑脊液中杀菌作用较弱，但     

Interindividual variability in biliary excretion of ceftriaxone: effects on biliary lipid metabolism and on intestinal microflora

Ceftriaxone is a broad spectrum parenteral cephalosporin that is eliminated through renal as well as biliary excretion. In order to characterize factors influencing the biliary excretion of ceftriaxone, and possible effects of this organic anion on biliary lipid transport, we studied six healthy volunteers before and during ceftriaxone infusion. The biliary secretion rates of cholesterol, bile acids, phospholipids and ceftriaxone were determined using a duodenal perfusion technique, and the biliary lipid composition and cholesterol saturation of stimulated hepatic bile were determined. Changes in the intestinal microflora induced by ceftriaxone treatment were also analysed. There was a three-fold interindividual variation in biliary excretion of ceftriaxone, and this was correlated with the secretion rate of bile acids (rs = 0.83, P = 0.05). During ceftriaxone infusion, the secretion rate of cholesterol was reduced by 32% (P less than 0.05), which resulted in a reduction of cholesterol saturation of bile, from 107 +/- 11 to 75 +/- 12% (SEM, P less than 0.05). The suppression of intestinal Escherichia coli and Bacteroides, and the proliferation of enterococci and lactobacilli were related to the biliary excretion of ceftriaxone. We conclude (i) that biliary excretion of ceftriaxone is of major importance for its effects on intestinal microflora, (ii) that secretion of this organic anion into bile is largely dependent on bile acid secretion, and (iii) that ceftriaxone inhibits the biliary secretion of cholesterol.     

头孢曲松泌尿系结石的理化分析

目的 探讨头孢曲松钠引发尿路结石的理化性质. 方法 2012年4月收检头孢曲松钠引发的儿童尿路结石2例.其中1例于2012年3月行头孢曲松钠治疗,过程中突发尿路结石,经治疗后自行排出沙粒状结石.另一例于2012年4月行头孢曲松钠治疗5d后突发下腹痛、呕吐,B超检查示右输尿管结石,KUB检查未见结石影,CT检查示右输尿管上段结石伴积水.保守治疗3d后结石排出,复查B超和IVU未见结石影.采用红外光谱、扫描电子显微镜及能谱仪分析2例尿路结石的成分. 结果 2例尿路结石样本均由头孢曲松和钙离子构成,摩尔比为1∶1. 结论 头孢曲松钠可引发尿石症,该结石具有X线下不显影的影像学特征,尿路结石成分为头孢曲松钙盐.     

Third-Generation Cephalosporin-Resistant Vibrio cholerae, India

Vibrio cholerae resistance to third-generation cephalosporins is rarely reported. We detected a strain that was negative for extended-spectrum β-lactamase and positive for the AmpC disk test, modified Hodge test, and EDTA disk synergy test and harbored the blaDHA-1 and blaNDM-1 genes. The antimicrobial drug susceptibility profile of V. cholerae should be monitored.     

Pharmacokinetics of intravenous and intraperitoneal ceftriaxone in chronic ambulatory peritoneal dialysis

Summary The kinetics of ceftriaxone was investigated in 8 patients without infection, who were receiving continuous ambulatory peritoneal dialysis (CAPD). Ceftriaxone 1 g was injected i.v. and 1 g was given intraperitoneally in the CAPD fluid during a 4-h dwell time. Ceftriaxone was assayed by HPLC. After intravenous administration, the kinetic parameters of ceftriaxone were: plasma t_1/2, 12.3 h, total plasma clearance, 14.0 ml/min, volume of distribution at steady state 0.18 l/kg, and peritoneal clearance 0.59 ml/min. Over 72 hours only 5.5% of the dose was eliminated by the peritoneal route. After intraperitoneal administration, ceftriaxone rapidly appeared in serum; the absorption t_1/2 was 1.1 h and the mean peak concentration was 38.8 µg/ml. The absorption of ceftriaxone from the peritoneal space was 39%. A single 1.0 g IP dose led to serum and dialysate concentrations of ceftriaxone above the minimum inhibitory concentration for susceptible pathogens for 24 hours.     

Single dose 1 g ceftriaxone for urogenital and pharyngeal infection caused by Neisseria gonorrhoeae

Objectives: To evaluate the efficacy of 1 g ceftriaxone in the treatment of urethritis, cervicitis and pharyngeal infection caused by Neisseria gonorrhoeae (N. gonorrhoeae) including the oral cephem‐resistant strain with chimera penicillin‐binding protein 2 (PBP‐2) (cefozopran‐resistant N. gonorrhoeae, CZRNG). Methods: From September 2004 to November 2006, 67 patients (27 male and 40 female) who had genital infection and/or pharyngeal infection caused by N. gonorrhoeae were enrolled in this study at five participating centers in Japan. To detect the chimera PBP‐2 gene, polymerase chain reaction (PCR) was performed using established primers against the altered penA of CZRNG isolates. All patients received a single 1 g dose of ceftriaxone. Efficacy was evaluated only in those who returned for examination and culture for N. gonorrhoeae between 3 and 14 days after the treatment. Results: CZRNG isolates detected by PCR accounted for 41.7% (20/48) of urogenital infections and 60.0% (15/25) of pharyngeal infections in the treatment efficacy evaluable cases. 37 of 39 CZRNG isolates (94.9%) were multi‐drug resistant isolates that had simultaneous resistance to penicillin, tetracycline, and ciprofloxacin. Nineteen patients had N. gonorrhoeae isolates in the urogenital area and pharynx simultaneously. Ceftriaxone treatment eradicated all N. gonorrhoeae isolates from 48 patients with genitourinary infection and 25 patients with pharyngeal infection. Conclusions: We report for the first time that ceftriaxone is effective in patients with gonococcal urethritis, cervicitis, and pharyngeal infection caused by CZRNG that has chimera PBP‐2.     

Pharmacokinetics of ceftriaxone following intravenous administration of a 3 g dose

Summary The pharmacokinetic parameters of total (bound and unbound) and free (unbound) ceftriaxone in six healthy volunteers after intravenous injection of 39 were compared with low-dose data from a previous study. The dose-dependent behaviour of total drug was considerably more pronounced after the 3 gram dose. In contrast, total body clearance (Cl _S ^F =258 ml/min), renal clearance (Cl _R ^F =170 ml/min) and volume of distribution (V _D(β) ^F =168 l) of free (unbound) drug did not differ from the data reported earlier. There was no significant change in biological half-life (t_1/2(β)=7.8 h) or in the fraction excreted unchanged in urine (f_u=0.67).