Aminoglycoside therapy Current use and future prospects

The microbiological, pharmacokinetic, toxicological and clinical aspects of aminoglycosides are reviewed. Aminoglycosides still have an important place in serious infections in neutropenic patients, endocarditis andPseudomonas aeruginosa infections, all in combination with beta-lactams. Monotherapy (with streptomycin) is indicated in less common diseases like tularaemia and bubonic plague. Several experimental studies support a oncedaily dosing regimen for aminoglycosides (comparable or better efficacy with less ototoxicity and nephrotoxicity). Only a very limited number of prospective comparative studies have been performed, and much more data on efficacy, development of resistance and toxicity is needed before once-daily administration can be recommended. The choice of an aminoglycoside should be based primarily on the local sensitivity patterns and cost. Differences in ototoxicity and nephrotoxicity are usually minor. If the acquisition costs of amikacin decline, it is to be expected that amikacin will be the aminoglycoside of choice.     

改进时间差攻击疗法治疗多重耐药阴沟肠杆菌的探究

[目的]研究利用改进的时间攻击疗法治疗多重耐药阴沟肠杆菌引起的感染的效果，并考究其与亚胺培南/西拉司丁治疗及传统时间攻击疗法的药物经济学成本/效果比。[方法]将38例明确诊断为产ESBLs阴沟肠杆菌感染且药敏结果皆为：对哌拉西林、环丙沙星、氧氟沙星、左旋氧氟沙星、庆大霉素、妥布霉素、头孢他啶、头孢噻肟、头孢哌酮、头孢曲松、头孢哌酮/舒巴坦、替卡西林/克拉维酸等皆耐药，而对亚胺培南/西拉司丁敏感的患者随机分为改进组、对照组、传统组。改进组患者先与磷霉素4g＋5%葡萄糖100ml于30min静脉滴注完毕后，再过30min立即给予阿米卡星0.4g＋0.9%NS250ml静脉滴注，上述治疗每日1次。对照组患者给予亚胺培南/西拉司丁1g＋0.9%NS250ml静脉滴注，每日3次。传统组患者先与磷霉素2g＋5%葡萄糖50ml静脉给予1h完毕后，立即给予阿米卡星0.2g＋0.9%NS100ml静脉滴注，上述治疗每日2次。疗程最长限为10d，其余检查治疗3组相同。考察3组的细菌清除率以及细菌清除所需的药物费用、不良反应的比较。[结果]改进组细菌清除率与对照组、传统组差异无统计学意义，并且改进组、传统组无不良反应，对照组有1例二重感染；而且改进组与对照组、传统组的细菌清除药物治疗费用差异有统计学意义。[结论]利用磷霉素＋阿米卡星的改进时间攻击差疗法能很好的治疗多重耐药的阴沟肠杆菌引起的感染，并且与采用亚胺培南/西拉司丁治疗方案及传统的时间攻击疗法相比具有较好的成本/效果比。     

豚鼠耳蜗外毛细胞凋亡时听力变化的实验观察

目的观察耳蜗外毛细胞发生凋亡时听力改变情况.方法对20只豚鼠药物造模,诱发耳蜗外毛细胞发凋亡.应用TUNEL技术观察凋亡表达,测试ABR阈值观察听力变化.结果应用丁胺卡那霉素1天即可诱发豚鼠耳蜗外毛细胞发生凋亡,连续应用3d,耳蜗外毛细胞凋亡呈强阳性表达,但ABR阈值无明显改变;随着用药时间延长,凋亡细胞数目增加,甚至出现部分毛细胞缺失现黎,此时ABR阈值明显升高.结论耳蜗外毛细胞发生凋亡早期对豚鼠听力无明显影响,随着耳毒性药物应用时间延长,豚鼠ABR阈值升高可能存在两种原因毛细胞凋亡或毛细胞坏死.     

丁胺卡那霉素地塞米松复方脂质体在兔眼玻璃体内的药代动力学研究

目的 应用丁胺卡那霉素地塞米松(丁卡地塞)复方脂质体玻璃体内注射以延长两种药物的半衰期.方法 大白兔随机分4组,正常眼2组和眼内炎眼2组均分别注射复方脂质体和游离药物.结果 丁卡在正常眼复方脂质体的半衰期较游离药物延长1.8倍,在眼内炎眼延长3.4倍.地塞在正常眼复方脂质体半衰期较游离药物延长22.5倍,在眼内炎眼延长46.2倍.结论 丁卡地塞复方脂质体玻璃体内注射使丁卡和地塞两种药物的半衰期有明显延长.     

两例EDTA依赖性假性血小板减少应用阿米卡星无效探讨

目的探讨2例乙二胺四乙酸(EDTA)依赖性假性血小板减少应用阿米卡星无效的机制。方法对2例EDTA依赖性假性血小板减少症患者的EDTA-K2抗凝血,在不同时间段分别加入阿米卡星,在血液分析仪检测,血涂片检查。结果该2名患者,加或不加阿米卡星,其血小板数均会随着时间的延长逐渐增加,其特征性的直方图也会随着时间的延长而消失,加入阿米卡星会获得更可靠的结果。结论阿米卡星并不能立即解离2例患者聚集的血小板,但随着时间延长,血小板缓慢解离,至4h达到相对稳定。1h内加入阿米卡星较为理想,相对普通EDTA抗凝可有效加速其解离过程,获得理想结果。     

An Evaluation of the Protective Effects of Thymoquinone on Amikacin-Induced Ototoxicity in Rats

Objectives

In this study we investigated the probable protective effects of thymoquinone on amikacin-induced ototoxicity in rats.

Methods

Thirty-two healthy rats were divided into four groups (amikacin, amikacin+thymoquinone, thymoquinone, and no treatment). Thymoquinone was fed to the rats via oral gavage in a dose of 40 mg/kg/day throughout the study period of 14 days. Amikacin was given by the intramuscular route in a dose of 600 mg/kg/day. Audiological assessment was conducted by the distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) tests, administered to all rats at the beginning of the study, and also on days 7 and 15. Biochemical parameters were calculated at the termination of the study to evaluate the oxidative status.

Results

There were significant decreases in DPOAE values and significant increases in ABR thresholds of the amikacin group on days 7 and 15, as compared to the amikacin+thymoquinone group. While ABR thresholds of the amikacin group increased significantly on days 7 and 15 as compared to their initial values, there were no significant differences between the initial and the 7th and 15th day values of ABR thresholds in the amikacin+thymoquinone group. Total oxidant status and oxidative stress index values of the amikacin+thymoquinone group were significantly lower than those of the amikacin group. Total antioxidant status values of the amikacin+thymoquinone group were significantly higher than those of the amikacin group.

Conclusion

Our study has demonstrated that the ototoxic effect brought forth by amikacin could be overcome with the concurrent use of thymoquinone.     

头孢类抗菌药物联合阿米卡星治疗白血病感染患者的疗效

目的探讨头孢类抗菌药物联合阿米卡星在治疗白血病患者化疗后粒细胞缺乏合并感染中的疗效,以提高临床诊治水平。方法选取2013年3月-2014年3月于医院接受治疗的白血病化疗后粒细胞缺乏合并感染患者92例,随机分为观察组与对照组,各46例,其中对照组给予头孢他啶联合阿米卡星治疗,观察组给予头孢吡肟联合阿米卡星治疗,对比分析两组的临床疗效。结果头孢他啶联合阿米卡星治疗后临床有效率80.43%,头孢吡肟联合阿米卡星治疗后临床有效率82.61%,两组比较差异无统计学意义;患者发生上呼吸道及肺部感染较为常见,两组感染部位比较差异无统计学意义;患者年龄(≥60岁或<60岁)、白血病治疗后缓解指标(完全缓解/部分缓解或无效)、粒细胞缺乏持续时间(≥10d或<10d)与疾病预后存在相关性(P<0.05)。结论头孢他啶联合阿米卡星与头孢吡肟联合阿米卡星治疗白血病化疗后粒细胞缺乏合并感染的临床有效率相当,且安全可靠,值得临床推广应用。     

Amikacin population pharmacokinetics among paediatric burn patients

Introduction

The objectives of this study were to (1) determine the pharmacokinetics of amikacin among children with severe burn and (2) identify influential covariates.

Methods

Population-based pharmacokinetic modelling was performed in NONMEM 7.2 for hospitalized children who received amikacin at 10–20 mg/kg divided two, three, or four times per day as part of early empiric treatment of presumed burn-related sepsis.

Results

The analysis included data from 70 patients (6 months to 17 years) with 282 amikacin serum concentrations. Amikacin's mean C_max was 33.2 ± 9.4 μg/mL and the mean C_min was 3.8 ± 4.6 μg/mL. The final covariate model estimated clearance as 5.98 L/h/70 kg (4.97–6.99, 95% CI), the volume of distribution in the central compartment as 16.7 L/70 kg (14.0–19.4, 95% CI), the volume of distribution in the peripheral compartment as 40.1 L/70 kg (15.0–80.4, 95% CI), and the inter-compartmental clearance as 3.38 L/h/70 kg (2.44–4.32, 95% CI). In multivariate analyses, current weight (P < 0.001) was a significant covariate, while age, sex, height, serum creatinine, C-reactive protein, platelet count, the extent and type of burn, and concomitant vancomycin administration did not influence amikacin pharmacokinetics.

Discussion

Children with burn featured elevated amikacin clearance when compared to healthy adult volunteers. However, peak amikacin concentrations are comparable to those attained in other critically-ill children, suggesting that elevated amikacin clearance may not result in sub-therapeutic antibacterial effects. In this study, we found that amikacin displays two-compartment pharmacokinetics, with weight exerting a strong effect upon amikacin clearance. Further pharmacodynamic studies are needed to establish the optimal dosing regimen for amikacin in paediatric burn patients.