Gentamicin in neonates at risk for sepsis – peak serum concentrations are not necessary

BACKGROUND:

Serum gentamicin concentrations (GSCs) are frequently obtained before and after gentamicin administration to newborns with, or at high risk for, sepsis.

OBJECTIVE:

To determine whether performing a peak GSC assay when the trough GSC is within the guidelines for care would add clinically relevant information for health care workers.

METHODS:

A retrospective review of the IWK Health Centre (Halifax, Nova Scotia) laboratory database for peak and trough GSC for infants <28 days after birth was performed.

RESULTS:

Of 5253 paired samples of trough and peak GSCs, 3001 (57%) had trough GSCs ≤2 μg/mL. Of these, only nine (0.3%) had a peak GSC >10 μg/mL.

CONCLUSIONS:

Performing a peak GSC measurement does not provide further clinically important data and increases patient morbidity and hospital costs.     

两个携带线粒体12S rRNA 1494C>T突变的耳聋家系的遗传学特征

Objective To evaluate the effect of mitochondrial DNA(mtDNA) secondary mutations,haplotypes,GJB2 gene mutations on phenotype of 1494C ＞ T mutation,and to study the molecular pathogenic mechanism of ma...     

一株特殊耐药表型肺炎克雷伯菌的耐药机制研究

目的 研究对氨基糖苷类抗生素产生特殊耐药现象（双抑菌圈）的肺炎克雷伯菌的耐药表型和耐药机制.方法 用K-B法、E-test法、三维试验等方法对其耐药表型进行研究.采用聚合酶链反应（PCR）技术对7种氨基糖苷类钝化酶基因、2种核糖体甲基化基因和Ⅰ类整合子进行检测,并对PCR产物测序.结果 细菌的这种特殊耐药表型是稳定的;PCR结果表明：这株菌含有Aac（3）-Ⅱ钝化酶基因、armA核糖体甲基化耐药基因和1000bp左右的Ⅰ类整合子.结论 这株菌对氨基糖苷类抗生素的耐药是多种耐药机制相互作用的结果.但是这尚不能满意地解释这种特殊的耐药现象,其机理有待进一步研究.     

Ototoxic drugs: Difference in sensitivity between mice and guinea pigs

The development of experimental animal models has played an invaluable role in understanding the mechanisms of neurosensory deafness and in devising effective treatments. The purpose of this study was to develop an adult mouse model of ototoxic drug-induced hearing loss and to compare the ototoxicity in the adult mouse to that in the well-described guinea pig model. Mice are a powerful model organism, especially due to the large availability of antibodies, probes and genetic mutants. In this study, mice (n = 114) and guinea pigs (n = 35) underwent systemic treatment with either kanamycin or cisplatin. Auditory brainstem responses showed a significant threshold shift in guinea pigs 2 weeks after the beginning of the ototoxic treatment, while there was no significant hearing impairment recorded in mice. Hair cells and neuronal loss were correlated with hearing function in both guinea pigs and mice. These results indicate that the mouse is not a good model for ototoxicity, which should be taken into consideration in all further investigations concerning ototoxicity-induced hearing loss.     

Suitability of a liquid chromatography assay of neomycin sulfate to replace the microbiological assay for neomycin in USP Monographs

The current USP National Formulary contains 65 Monographs for drug formulations containing neomycin. All 65 Monographs prescribe a bioassay for neomycin assay. This bioassay, based on cell culture, is labor intensive, has poor precision, and cannot be adapted for purity or identification. High-performance anion-exchange chromatography with integrated pulsed amperometric detection (HPAE-IPAD), a liquid chromatography technique, has been shown to be suitable for neomycin purity analysis and neomycin assay of an over-the-counter first aid cream (Hanko and Rohrer [17]). Here we propose that an HPAE-IPAD assay can replace the bioassay in the 65 neomycin-containing Monographs. We applied the HPAE-IPAD assay to four neomycin-containing drug products representing the four classes of formulations found in the 65 Monographs, liquid, solid, suspension, and cream. Each drug was analyzed with two chromatography systems, and on 3 separate days. For all products, HPAE-IPAD measurements were precise and accurate with respect to the label concentrations. There was also high accuracy for spike recovery of neomycin from the four drug products throughout 70–150% of the labeled concentration. These results suggest that an HPAE-IPAD assay would be an accurate assay for neomycin, and would be faster and more precise than the current bioassay.     

64株大肠埃希菌对氨基糖苷类抗生素的耐药表型与钝化酶基因型的分析

目的 调查2004年北京地区临床收集的耐庆大霉素大肠埃希菌对氨基糖苷类抗生素的敏感性和氨基糖苷类钝化酶基因的流行状况.方法 采用微量肉汤稀释法检测64株大肠埃希菌对16种氨基糖苷类抗生素的最低抑菌浓度（MIC）值;利用巢式PCR方法对其可能含有的7种氨基糖苷类钝化酶基因进行检测和确证.结果 临床大肠埃希菌的耐药表型较为复杂,与钝化酶基因表达有关.测试菌株中存在aac（3）-Ⅱc、aac（6＇）-Ⅰ b、ant（2＂）-Ⅰ a和ant（3＂）-Ⅰ a 4种耐药基因,aac（3）-Ⅱc和aac（6′）-Ⅰ b是主要的产酶基因.约40%的耐药菌中存在2种或2种以上的钝化酶基因.结论 产生氨基糖苷类钝化酶是临床分离的大肠埃希菌对氨基糖苷类抗生素主要的耐药机制.采用巢式PCR方法检测耐药基因,特别是在缺少阳性对照菌株的情况下,可以保障检测结果的特异性和准确性.临床菌的耐药表型和钝化酶基因关系较为复杂,这可能与耐药菌中尚存在其他耐药基因有关.     

Pharmacokinetics of once and twice daily dosing of intravenous tobramycin in paediatric patients with cystic fibrosis

The optimal dosing of intravenous tobramycin for treatment of pulmonary exacerbations in paediatric cystic fibrosis (CF) patients has not been completely delineated. We performed a retrospective study evaluating the pharmacokinetics and pharmacodynamics of once daily dosing (ODD) of IV tobramycin compared to twice daily dosing (TDD). Fifty-nine and 44 patients were included in the ODD and TDD groups, respectively. Once daily dosing achieved higher C_max as compared to TDD (29.5?±?11.0 vs 19.0?±?4.9, P?P?P?C_max:MIC for MICs >1.0?mg/l. Twice daily dosing may be a viable alternative to ODD in treating organisms with MICs ≤?1.0?mg/l; however, with MICs >1.0?mg/l, ODD is likely necessary to achieve goal C_max:MIC ratios.     

Rapid mass screening method and counseling for the 1555A?G mitochondrial mutation

The 1555A?G point mutation is associated with a susceptibility to aminoglycoside antibiotics, and is of particular interest, as it may cause hearing loss even without aminoglycoside exposure. There may be a considerably large high-risk population in Japan, and to avoid possible side effects in this group, a rapid mass screening system and careful counseling are recommended. We are currently using the mutant allele specific amplification (MASA) method to detect the 1555A?G mitochondrial mutation and we distribute a warning card to subjects found to bear this mutation.     

卡托普利对糖尿病合并肺结核应用氨基糖甙类药物时肾脏的保护作用

目的 观察卡托普利对糖尿病合并肺结核患者应用氨基糖甙类药物时对肾脏的保护作用?方法 85例糖尿病合并肺结核患者 ,随机分为治疗组 ( 44例 )与对照组 ( 41例 )?两组抗痨方案均含氨基糖甙类药物?治疗组在 2个月强化治疗期间加服卡托普利?治疗前及强化治疗结束时检测尿微量白蛋白?β2 —微球蛋白?血清肌酐及肌酐清除率并进行比较?结果 治疗组 β2 -微球蛋白较治疗前显著降低 (P<0 0.5),其余各项指标无明显变化?对照组尿微量白蛋白和 β2 -微球蛋白显著增加 (P<0 0.1 ,P<0 0 5)?结论 卡托普利对长期应用氨基糖甙类药物患者的肾脏有一定的保护作用?     

铜绿假单胞菌氨基糖苷类耐药表型及耐药基因的检测

目的了解中山地区铜绿假单胞菌氨基糖苷类药物的耐药表型和基因表型的分布及其关系。方法采用VITEK-2Compact高级专家系统判定2010年1-9月896株铜绿假单胞菌对氨基糖苷类药物的耐药表型,并对其中15株多药耐药铜绿假单胞菌采用PCR的方法检测4种氨基糖苷类修饰酶基因。结果 896株铜绿假单胞菌及15株多药耐药铜绿假单胞菌对氨基糖苷类药物的耐药表型模式均主要为表型模式RESISTANT(GEN、NET、AMI、TOB),阳性株分别为468、12株;15株多药耐药菌株全部检出氨基糖苷类耐药基因:aac(6′)-Ⅰ、aac(6′)-Ⅱ、ant(2″)-Ⅰ、ant(3″)-Ⅰ分别为13、4、3、8株。结论临床分离的铜绿假单胞菌以单一耐药表型模式为主,推测该地区氨基糖苷类药物耐药的主要原因,是氨基糖苷类修饰酶基因的存在导致。