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.     

高效液相色谱法测定硫酸奈替米星注射液的含量

目的采用高效液相色谱法测定硫酸奈替米星及注射液的含量。方法以μ-Diamonsil—C18为分析柱，流动相为1．5％的磷酸二氢钾-乙睛，流速为1．0ml／min，检测渡长为205nm。含量测定用峰面积外标法。结果硫酸奈替米星在0．1—1．6mg／ml浓度范围内呈现良好线性关系，r=0．9998．平均回收率为99．5％，RSD=0．4％（n=9）。结论本方法操作简便、快速，结果准确可靠，重现性好，均能很好地满足质量控制的要求，为开辟氨基糖苷类抗生素含量测定的仪器提供了一定借鉴。     

Neoadjuvant Chemotherapy for Patients with Synchronous Multifocal Osteosarcoma: Results in Eleven Cases

Abstract

Between January 1995 and December 1999, 11 patients with synchronous multifocal osteosarcoma (SMO) received neoadjuvant treatment with high-dose methotrexate, cisplatinum, Adriamycin, and ifosfamide. After primary chemotherapy in 4 patients who had only two bone localizations, it was possible to treat all tumor foci locally. The remaining patients, with more than three bones involved, were treated surgically only in 3 cases at the primary site, while secondary lesions did not receive any treatment.

The final results of our study were disappointing. All patients died of the tumor 6 to 24 months after the beginning of treatment (mean 11.9 months). Nevertheless, the survival time of the 4 patients with locally treated lesions was significantly longer than the one of 7 patients in whom the secondary lesions were not locally treated (18.2 vs 9.1 months; P<0.008). It should be noted that those patients simultaneously operated on two sites, the response to chemotherapy of “primary” and “secondary” lesions was always similar. This homogeneity supports the thesis that in synchronous multifocal osteosarcoma the tumors are not multicentric in origin but represent bone-to-bone metas-tases from a monocentric tumor.     

小切口及术中硫酸奈替米星局部治疗急性化脓性阑尾炎合并腹膜炎临床分析

目的：探讨小切口加硫酸奈替米星局部治疗化脓性阑尾炎合并腹膜炎的疗效。方法以224例化脓性阑尾炎者为此次的探究主体,随机将其分组。观察组接受的术式是小切口,同时应用硫酸奈替米星。对照组则选用传统的术式。结果在所需的手术时间以及切口长度等指标方面进行比较,观察组手术情况要好于对照组。随访术后切口的恢复,发现观察组效果明显较好。其中观察组切口出现脂肪液化现象的仅有3例,其他皆完全恢复。而对照组有12例患者出现了脂肪液化现象。其余有4例发生腹腔感染,切口疝3例。P〈0.01,两组间的差异存在统计学意义。结论小切口的术式可以较好的治疗合并有腹膜炎的阑尾炎者,同时使用硫酸奈替米星可以进一步的提高治疗。     

奈替米星的临床研究

目的研究来替米星每日1次投药法治疗下呼吸道感染的临床效果、药代动力学、抗生素后效应和药物毒性。方法48例患者分为三组：（1）单一组14例,使用奈替米星,每天总量为6mg·kg-1·h-1;（2）合用组16例,使用头孢唑啉每12小时1次投药3g,奈替米星每天200mg;（3）对照组18例,使用头胞唑啉每12小时投药3g,与阿米卡星每天200mg联合使用,分别观察临床症状、实验室检查及临床疗效;应用荧光偏振分析仪（TDX）药物浓度自动分析仪研究其药代动力学;应用AVANTAGE生物分析仪研究奈替米星抗生素后效应,观察了奈替米星的肾、耳毒性。结果每日1次单用奈替米星组疗效较头抱叹批及阿米卡星组好。平均血药浓度为27．23mg／L谷浓度为0．23mg／L,半数药物消除相时间为5．095小时,药时曲线下面积为70μg·h-1·ml-1。奈替米皇0．5、1及4倍最低抑菌浓度（MIC）对4种细菌均显示不同程度的抗生素后效应。本组研究未发现耳、肾毒性。结论奈替米星每日1次投药法有较高血清浓度,较大药时曲线下面积,作为浓度依赖性杀菌药,此药临床效果较好,而且其抗生素后效应时间较长。     

氨基糖苷类抗生素所致豚鼠耳毒性与耳蜗毛细胞凋亡的关系

目的:研究氨基糖苷类抗生素所致的豚鼠听力损伤与其耳蜗毛细胞凋亡之间的关系。方法:将36只豚鼠随机分为生理盐水对照组、庆大霉素组和奈替米星组,连续给药14d,利用TUNEL法原位检测动物耳蜗毛细胞的凋亡情况。结果:生理盐水对照组豚鼠耳蜗未见凋亡毛细胞,庆大霉素组豚鼠耳蜗基底回内外毛细胞均消失,第3回中第1排外毛细胞消失,第2,3排外毛细胞发生凋亡,第2回中第1,2排外毛细胞发生凋亡。而奈替米星组豚鼠耳蜗基底回中第1,2排外毛细胞丢失,第3排外毛细胞发生凋亡,第3回中第1排外毛细胞丢失,第2排外毛细胞发生凋亡。第2回毛细胞中仅见第1排外毛细胞凋亡。结论:给予豚鼠庆大霉素或奈替米星后均可引起其听力损伤;其耳毒性的产生可能与其引起的耳蜗毛细胞凋亡密切相关。     

金纳多对奈替米星致耳毒性模型豚鼠的预防和治疗作用研究

目的:研究金纳多注射液对奈替米星导致豚鼠耳毒性的预防和治疗作用。方法:将48只豚鼠随机分成生理盐水对照组、奈替米星组、金纳多预防组和金纳多治疗组,以不同方式给药4wk后,比较各组豚鼠的耳廓反射阈、脑干诱发电位、Ⅲ波时间、血清铁离子浓度和SOD活性以及耳蜗毛细胞扫描电镜图。结果:4wk后金纳多预防组和金纳多治疗组的耳廓反射阈、脑干诱发电位、Ⅲ波时间分别为(33.75±4.20)dB、(25.63±3.71)dB、(3.91±0.18)ms和(27.27±4.54)dB、(32.95±4.30)dB、(4.30±0.16)ms,2组间比较存在显著性差异(P<0.01)。结论:金纳多注射液能预防和治疗奈替米星引起的豚鼠耳毒性,而且预防给药对耳毒性的改善作用大于治疗给药。     

丽春红G为探针的共振散射法测定奈替米星的含量

目的建立一种共振散射(RS)技术测定奈替米星含量的新方法。方法在pH3.78 Britton-Robinson的缓冲液中,奈替米星与丽春红G反应形成离子缔合物,在荧光分光光度计上同步扫描(λex=λem),体系的共振散射信号增强,并产生新的共振散射光谱,最强的散射峰位于577nm。同时观察了奈替米星与丽春红G反应的适宜条件和对共存物质的影响。结果在波长为577nm处,奈替米星浓度在0.12~10.5μg/ml范围内与RS强度呈良好的线性关系,回归方程为△IRs=7.79c-1.38,相关系数为0.9981,方法的检测限为28.5ng/ml,并用于硫酸奈替米星注射液的测定,回收率在94.70%~106.0%之间。结论该法简便、快速、选择性好、灵敏度高,用于奈替米星含量测定,结果满意。     

Auditory function in guinea pigs treated with netilmicin and other aminoglycoside antibiotics

Summary The following aminoglycoside antibiotics netilmicin, sisomicin, gentamicin, and kanamycin were submitted to a comparative study of their ototoxicity using both reflexological (Preyer's pinnareflex) and electrophysiological (near and far field) methods. The daily s.c. administration of sisomicin, gentamicin, and kanamycin for 21 days provoked a dose-related impairment of the cochlear function, detected with all the employed techniques. On the other hand, a very low ototoxic effect of netilmicin was demonstrated with electrophysiological but not with the reflexological evaluation.The reliability of the methods used in these experiments is also compared.     

Studies on drug monitoring in thrice and once daily treatment with aminoglycosides

Objectives To investigate at what time the peak level should be determined under conventional thrice daily (t.i.d.) administration of the aminoglycoside netilmicin and to study its serum concentrations under once daily (od) treatment to define the required daily dose and to gain information about convenient drug monitoring.Design The design of the study was a consecutive sample trial.Setting The study took place in a university hospital.Patients 41 intubated patients of a surgical ICU who received netilmicin as a short-term infusion over 30 min for life-threatening infections were included in the study.Interventions In 21 patients netilmicin was administered t.i.d. The virtual peak levels which had been determined by pharmacokinetic dosage calculation were compared with the serum concentrations obtained directly after the administration as well as after 15, 30, 60 and 180 min. In 20 patients the netilmicin serum concentrations during od treatment were determined directly before and immediately after the application as well as 0.5, 1, 3, 7 and 12 h later. To achieve a virtual peak level of 25 mg/l and a trough level of 0.5 mg/l individual adjustment of the dosage based on pharmacokinetic calculations was performed.Measurements and results In t.i.d. treatment the serum concentration measured after 30 min was closest to the virtual peak level; therefore, this is the best time to determine the peak level. In od treatment the required daily dose was 7.86 mg/kg body weight (median) in patients with normal renal function. During od dosing the trough level was extremely important in drug monitoring, whereas determination of the high peak level was of doubtful value.Conclusions The peak level should be determined during t.i.d. administration at 30 min. In od treatment the initial daily dose should be 7 mg/kg body weight; in drug monitoring the trough level is very important.