High-level amikacin resistance in Pseudomonas aeruginosa associated with a 3'-phosphotransferase with high affinity for amikacin

This work describes the characterization of the phosphotransferase enzymatic activity responsible for amikacin resistance in two clinical Pseudomona aeruginosa strains, isolated from a hospital that used amikacin as first-line aminoglycoside. Amikacin-resistant P. aeruginosa PA40 and PA43 (MIC: 128 mg/l) were shown to have APH activity with a substrate profile similar to that of APH(3′)-VI. The enzyme from P. aeruginosa PA40 was purified to >70% homogeneity. The K_m of amikacin for this enzyme was 1.4 μM, the V_max/K_m ratio for amikacin was higher than for the other aminoglycosides tested and PCR and DNA sequencing ruled out the presence of aph(3′)-IIps. Amikacin resistance in this strain was, therefore, associated with APH(3′)-VI and the high affinity of this enzyme for amikacin could explain the high-level resistance that we observed.     

临床常用氨基糖苷在烫伤兔体中的药动学改变

１７只家兔烫伤前和烫伤后７天静脉注射庆大霉素３ｍｇ／ｋｇ（ｎ＝７）和丁胺卡那霉素１０ｍｇ／ｋｇ（ｎ＝１０）的药动学资料比较的结果表明，２０％体表面积三度烫伤后家兔的庆大霉素和丁胺卡那霉素血浓度均明显下降；两药分布容积（Ｖ＿ｄ）均增加，半衰期（ｔ＿（１／２））缩短和药时曲线下面积（ＡＵＣ）减小。本实验证实，烫伤能改变庆大霉素和丁胺卡那霉素的药动学井导致伤后两药血浓度降低。     

阿米卡星全日剂量单次用药治疗下呼吸道感染的评价

对３５例耳、肾功能正常的下呼吸道细菌感染患者采用阿米卡星全日剂量单次给药评价其临床疗效及不良反应。结果表明,单次用药疗效与二次用药比较无明显差异。单次用药治疗前、后肾功能无明显变化,２例患者出现听力下降,但２周内恢复正常。二次用药治疗后３例病人尿β２－微球蛋白（β２－ＭＧ）、血α１－微球蛋白（α１－ＭＧ）出现异常变化;２例出现感音神经性耳聋患者１月内未恢复正常。提示：在获得满意疗效的同时,为有效降低不良反应,１５ｍｇ／ｋｇ全日剂量单次用药对患者更为有利。     

阿米卡星在不同年龄呼吸系统感染病人中的药物动力学

为研究阿米卡星（ＡＭＫ）在不同年龄呼吸系感染病人中的药物动力学特性,采用荧光偏振免疫法（ＦＰＩＡ）测定病人血中ＡＭＫ浓度,根据药－时数据求出药物动力学参数。结果表明,ＡＭＫ在青年病人组和老年病人组中的末端相消除半衰期分别为３．０２±０．６３ｈ和４．４８±１．３９ｈ,老年病人组明显长于青年病人组（Ｐ＜０．０５）。药物峰浓度分别为３８．７０±７．５１ｍｇ／Ｌ和４０．０６±５．３０ｍｇ／Ｌ,两组间无差异。研究证明,在肾功正常的条件下,年龄因素是影响ＡＭＫ消除半衰期的重要因素之一,但不影响药物峰浓度及其它药物动力学参数。因此,老年病人应用ＡＭＫ时应进行血药浓度监测     

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.     

抗生素89—07,庆大霉素和阿米卡星的耳毒性比较

采用听性脑干电反应，眼震电图，结合火棉胶切片，耳蜗铺片琥珀酸脱氢酶染色方法和扫描电等形态学观察。综合主人抗生素８９－０７与阿米卡星、庆大霉素的耳毒性。结果表明：ＧＭ１００ｍｇ确有耳蜗系和前庭系毒性；ＡＭＫ２００ｍｇ对耳蜗第有轻度损伤，而抗生素８９－０７ ２５、５０、１００ｍｇ对耳蜗均无损伤。     

硫酸奈替米星与阿米卡星治疗重症监护病房中肺部感染的疗效比较

将重症监护病房１１９例继发肺部感染病人随机分成两组，分别给予硫酸奈替米星３００ｍｇ／ｄ或阿米卡星６００ｍｇ／ｄ治疗，根据临床表现、白细胞计数、痰培养、胸片及肝肾功能等其它辅助检查，观察其疗效及不良反应。结果显示：硫酸奈替米星有效率（７９．７％）比阿米卡星（５７．８％）高；辅助检查中白细胞计数、胸片恢复正常率和痰培养转阴率前组均高于后组，而不良反应前组低于后组。本文认为：对重症监护病房肺部感染初期，痰培养及药敏尚未确定的病人，给予硫酸奈替米星３００ｍｇ／ｄ短程治疗是有效且安全的方案，尤其对老年人、小儿和有轻度肾功能损害者，在严密肾功能监护下，可有针对性使用，故硫酸奈替米星具有较大的临床使用价值     

Ⅲ、Ⅳ期老年糖尿病褥疮感染的综合护理探讨

目的探讨III、Ⅳ期老年糖尿病褥疮感染的综合护理措施。方法将100例老年糖尿病褥疮感染患者通过随机数字表法随机分为两组。两组均在常规综合护理的基础上进行换药,实验组50例采用过氧化氢溶液创面冲洗,丁胺卡那霉素消毒,济安舒能喷洒并结合红外线照射创面的方法;而对照组50例采用2.5%碘伏溶液消毒,红外线照射创面,0.02%呋喃西林液湿敷创面的常规换药方法。观察两组的治疗效果和临床愈合时间。结果实验组总有效率100%,明显高于对照组的82.0%。实验组治愈时间为（14.12±3.27）d,明显短于对照组的（24.37±3.87）d,二者相比均有显著性意义,P〈0.05。结论丁胺卡那霉素消毒,济安舒能喷洒并结合红外线照射创面,同时施行“个性化”结合综合护理治疗老年糖尿病褥疮疗效显著,能缩短治疗时间,对患者无不良反应,是安全、有效,值得推广的合理治疗护理方法。     

抗生素89－07对前庭器功能形态影响的观察

给豚鼠肌注抗生素８９－０７并用旋转试验评价前庭功能。２８天后用扫描电镜观察前庭壶腹嵴、椭园囊斑、球囊斑的形态改变，检测比较８９－０７与ＡＭＫ及ＧＭ对前庭器的影响，结果表明：８９－０７对前庭无明显损害，对前庭功能的影响与生理盐水组相比较没有显著差异，在大剂量时８９－０７虽对耳石膜有损害，并使感觉毛细胞的纤毛粘连，但８９－０７对前庭的毒性作用仍比庆大霉素及丁胺卡那霉素小得多。     

The effect of guanidine on the accumulation of amikacin in guinea pig renal cortical slices

The role of a recently identified organic ion transport system in the accumulation of the aminoglycoside (AG), amikacin (AK) in the kidney was investigated in the present study. Because this transport system has been characterized as being a carrier for the organic cation, guanidine, the effect of guanidine on the uptake of AK into renal slices from guinea pig was examined. Renal slices incubated in medium containing AK concentrated the drug against a concentration gradient (i.e. slice: mediratio (S/M) > 1.0). This uptake was significantly reduced when an equimolar concentration (1 × 10⁻⁵ M) of another AG, gentamicin was added to the incubation medium. In contrast, AK uptake was relatively insensitive to the presence of the cation, tetraethylammonium (TEA) in the medium. Guanidine was also ineffective at inhibiting AK uptake into slices and reduced AK uptake by only 22% at guanidine concentrations of 1 × 10⁻² M. In comparison, TEA was slightly more sensitive to the presence of guanidine in the incubation media since TEA uptake was reduced by 22% at guanidine concentrations of 1 × 10⁻³ M and reduced by approximately 70% at guanidine concentrations of 1 × 10⁻² M. Thus, the results of the present study suggest that the guanidine transport system does not play a role in the renal accumulation of AK since the presence of guanidine in the incubation medium had little effect on the accumulation of AK into renal cortical slices.