Interleukin-10/Ceftriaxone prevents E. coli-induced delays in sensorimotor task learning and spatial memory in neonatal and adult Sprague-Dawley rats

Intrauterine infection during pregnancy is associated with early activation of the fetal immune system and poor neurodevelopmental outcomes. Immune activation can lead to alterations in sensorimotor skills, changes in learning and memory and neural plasticity. Both interleukin-10 (IL-10) and Ceftriaxone have been shown to decrease immune system activation and increase memory capacity, respectively. Using a rodent model of intrauterine infection, we examined sensorimotor development in pups, learning and memory, via the Morris water maze, and long-term potentiation in adult rats. Pregnant rats at gestational day 17 were inoculated with 1 × 10⁵ colony forming units of Escherichia coli (E. coli) or saline. Animals in the treatment group received IL-10/Ceftriaxone for 3 days following E. coli administration. Intrauterine infection delayed surface righting, negative geotaxis, startle response and eye opening. Treatment with IL-10/Ceftriaxone reduced the delay in these tests. Intrauterine infection impaired performance in the probe trial in the Morris water maze (saline 25.13 ± 1.01; E. coli 20.75 ± 1.01; E. coli + IL-10/Ceftriaxone 20.2 ± 1.62) and reduced the induction of long-term potentiation (saline 141.5 ± 4.3; E. coli 128.7 ± 3.9; E. coli + IL-10/Ceftriaxone 140.0 ± 10). In summary, the results of this study indicate that E. coli induced intrauterine infection delays sensorimotor and learning and memory, while IL-10/Ceftriaxone rescues some of these behaviors. These delays were also accompanied by an increase in interleukin-1β levels, which indicates immune activation. IL-10/Ceftriaxone prevents these delays as well as decreases E. coli-induced interleukin-1β activation and may offer a window of time in which suitable treatment could be administered.     

头孢曲松治疗大白兔实验感染鼠疫疗效观察

目的观察不同剂量头孢曲松对鼠疫的治疗效果。方法将80只新西兰大白兔随机分为对照组和治疗组,治疗组按给不同剂量的头孢曲松(400、150、50mg/kg)分为3组。强毒鼠疫菌141株,37℃培养24 h,将培养物稀释成含菌20亿/ml,在大白兔鼠鼷部皮下接种,每只1 ml。24 h后治疗组按400、150、50 mg/kg静脉注射头孢曲松,每天分2次给药,连续给药9 d。观察4组动物精神状态、食量、饮水、被毛、并测量体温,死亡动物取腺、肝、脾、肺、心做鼠疫细菌学培养。存活动物于停药后第9天心脏采血并处死,进行鼠疫细菌学培养和间接血细胞凝集试验(IHA)。结果对照组动物全部死亡,各脏器细菌学培养均分离到鼠疫菌。治疗组大白兔死亡21只,头孢曲松400、150、50 mg/kg组的治愈率分别为45．16%、80．00%、93．30%,组间比较差异有统计学意义(X~2=17．395,P＜0．005)。存活的大白兔在停药后第9天全部处死,各脏器鼠疫细菌学培养阴性,IHA均为阳性,滴度介于1：40～1：20 480。结论头孢曲松可用于鼠疫的临床治疗,但要注意治疗剂量,剂量过高同样会降低治愈率,增加死亡率。     

Randomized controlled monocentric comparison of once daily ceftriaxone with tobramycin and cefotaxime three times daily with tobramycin in neutropenic fever

 A prospective, randomized, controlled monocentric trial was performed to evaluate the efficacy and safety of once daily ceftriaxone 2 g plus tobramycin 5 mg/kg in comparison to cefotaxime 2 g t.i.d. plus tobramycin 5 mg/kg qd in the treatment of neutropenic fever. In cases of fever ≥38.5  °C and a neutrophil count below 1000/μl, patients with hematological malignancies were assigned to ceftriaxone or cefotaxime, each with tobramycin. The primary endpoint was defined as defervescence <37.5  °C on day 4–6 followed by at least 7 afebrile days. Secondary endpoints were overall response, defined as defervescence on day 25 and toxicity. There were 160 episodes of 114 patients included. Fever of unknown origin accounted for 79 episodes (51%), microbiologically defined infection for 36 (23%), clinically defined infection for 27 (17%), and both clinically and microbiologically defined infection for 14 episodes (9%). On an intent-to-treat basis 156 episodes could be evaluated for the primary endpoint. Ceftriaxone plus tobramycin and cefotaxime plus tobramycin resulted in a primary response in 46.9% and 45.3%, respectively. Overall response was achieved on study day 25 in 87.7% and 80%, respectively. No significant difference in toxicity was observed. Once-daily ceftriaxone plus tobramycin was not inferior to cefotaxime t.i.d. plus tobramycin qd in the empirical treatment of neutropenic fever. Received: 29 October 1999 / Accepted: 28 August 2000     

保妇康栓联合头孢曲松钠、甲硝唑治疗慢性盆腔炎的临床研究

目的观察保妇康栓联合头孢曲松钠、甲硝唑治疗慢性盆腔炎的临床疗效。方法选取2013年6月—2014年6月西安市第九医院收治的慢性盆腔炎患者80例,随机分为对照组和治疗组,每组40例。对照组患者给予注射用头孢曲松钠2.0 g加入生理盐水250 m L,静脉滴注,1次/d;同时静脉滴注甲硝唑葡萄糖注射液250 m L,1次/d。治疗组在对照组基础上,月经结束后3 d开始睡前使用保妇康栓,1次/d。两组均连续治疗21 d。观察两组的临床疗效,同时比较两组临床症状改善情况、炎症因子检测水平、超声检查情况及复发率。结果治疗后,对照组和治疗组的总有效率分别为72.5%、92.5%,两组总有效率比较差异有统计学意义(P0.05)。治疗后,两组患者的临床症状及影像学检查均较治疗前明显好转,且治疗组优于对照组(P0.05)。两组患者TNF-α、IL-8、TGF-β1、IL-1β均较同组治疗前显著降低,同组治疗前后差异有统计学意义(P0.05);且治疗组这些观察指标的改善程度优于对照组,两组比较差异有统计学意义(P0.05)。对照组和治疗组的复发率分别为17.5%、2.7%,两组复发率比较差异有统计学意义(P0.05)。结论保妇康栓联合头孢曲松钠、甲硝唑治疗慢性盆腔炎具有较好的临床疗效,可减轻患者的临床症状,降低炎症因子水平,在临床具有一定的推广应用价值。     

New treatment options for infections caused by increasingly antimicrobial-resistant Neisseria gonorrhoeae

The emergence of high-level resistance to ceftriaxone is giving rise to serious concern about absence of effective treatment options to cure gonococcal infections. Increasing the dosage regimen can be applied to ceftriaxone and azithromycin, but the emergence of high-level resistance has already been reported. Spectinomycin is another active drug but has low efficacy in the treatment of pharyngeal gonorrhoea. Conventional antibiotics could be introduced for gonococcal treatment, but they have some limitations, such as the absence of clinical trials and breakpoint. Combining antibiotics is another promising method to cure patients and to prevent the emergence of resistance. The most important strategy to maintain the efficacy of antibiotics is rapid detection and dissemination control of novel resistant isolate.     

Pharmacokinetic-pharmacodynamic comparison of ceftriaxone regimens in acute cholangitis

The most important factors determining the prognosis of patients with acute cholangitis (AC) are prompt biliary drainage and appropriate choice of antibiotics. This study was performed to evaluate whether dividing the number of doses based on the PK-PD theory contributes to better clinical outcome in the management of acute cholangitis. We measured ceftriaxone levels in blood and bile in 21 cases diagnosed with moderate-to-severe AC. Eleven cases were administered 2 g of ceftriaxone once-daily (group A) and 10 cases were given 1 g of ceftriaxone twice-daily (group B). The theoretical effect of ceftriaxone was evaluated by pharmacokinetic–pharmacodynamic (PK–PD) parameters. Clinical efficacy was evaluated by body temperature, white blood cell count and serum levels of C-reactive protein. Minimum level of ceftriaxone in serum (in mg/L) in groups A and B at 24 h after the first dose was 9.1 and 9.2, whereas that in bile was 2.9 and 2.5, respectively. The minimum inhibitory concentration (MIC) of ceftriaxone for all isolated bacteria was below the minimum serum and biliary concentration of ceftriaxone 24 h after the first administration (except for Enterococcus species). The MIC for isolated bacterial strains was <16 mg/L, which is the PK–PD breakpoint for ceftriaxone at 2 g/day. Both regimens showed clinical efficacy and did not contradict the effect predicted based on PK–PD.     

头孢曲松钠治疗儿童鼠伤寒沙门氏菌肠炎疗效分析

目的探讨头孢曲松钠治疗儿童鼠伤寒沙门菌肠炎的临床疗效。方法总结该院2005年1月—2012年8月鼠伤寒沙门菌肠炎患儿86例,其中头孢曲松钠组60例,美洛西林钠/舒巴坦钠组26例,通过检查两组患儿的大便情况及常规检查,分析头孢曲松钠对儿童鼠伤寒沙门菌肠炎的疗效。结果头孢曲松钠组总有效率78.3%,美洛西林钠舒巴坦钠组有效率11.5%,两者疗效比较,差异有统计学意义(P<0.05)。结论头孢曲松钠治疗鼠伤寒沙门菌有效率高,耐药者少,治疗效果好。     

淋病奈瑟菌头孢曲松敏感株和耐药株双向凝胶电泳试验

目的应用双向凝胶电泳试验初步分离淋病奈瑟菌头孢曲松临床敏感株和诱导耐药株的差异蛋白质。方法分别提取两种细菌的总蛋白,进行等电点聚焦和SDS-聚丙烯胺凝胶电泳,对所得胶图利用Im-ageMaster5.0软件进行分析。结果得到了分辨率和重复性均好的双向凝胶电泳图谱,通过分析得到1.3倍差异点24个。结论通过双向凝胶电泳试验,分离出淋病奈瑟菌头孢曲松临床敏感株和诱导耐药株之间的差异表达蛋白。     

舒血宁注射液加重头孢曲松钠致凝血障碍1例

1例31a男性患者,因治疗病毒性脑炎继发的细菌感染,静脉输入注射用头孢曲松钠2g＋0.9%氯化钠注射液100mL。7d后,患者双前臂静脉输液处瘀斑扩大,查凝血象：PT15.2s,INR1.31,APTT16.9s,Fbg1.00g·L-1,TT22.8s。怀疑药源性凝血障碍,停用头孢曲松钠,肌内注射维生素K1每天10mg。为改善微循环,第2天静脉滴注舒血宁注射液20mL＋0.9%氯化钠注射液500mL,7d后患者凝血象PT34.1s,INR2.87,APTT超出检测范围,Fbg0.70g·L-1,TT22.9s,遂停用舒血宁注射液,4d后凝血象基本恢复正常。     

药物性胆囊假性结石的超声鉴别诊断

目的:分析头孢曲松钠致胆囊内假性结石的超声图像特征。方法:采用超声诊断仪对9例使用头孢曲松钠致胆囊内假性结石的患者胆囊进行多切面扫查,仔细观察结石形态、回声强度、后方声影的强弱及变换体位后的移动情况,随访停药后的结石变化。结果:9例患者中,超声检查结果:2例单发,7例多发;形态及边缘规则1例,不规则6例,泥沙状2例;9例可见结石内部回声;较弱声者9例;移动、沉降速度快者1例,缓慢者8例。结论:静脉使用头孢曲松钠后会产生假性胆囊结石,与一般胆囊结石相比,具有特征性的超声特点,停药后短期内可恢复正常。应针对其图像特征,与胆囊结石鉴别,避免不必要的手术治疗,以免给患者带来不必要的痛苦甚至引发医疗纠纷。