Atracurium and vecuronium interaction with gentamicin and tobramycin

Drug interactions between the aminoglycosides (tobramycin and gentamicin) and atracurium and vecuronium were studied prospectively in 44 patients. Twenty-two patients had therapeutic serum levels of tobramycin or gentamicin and 22 served as controls. Onset time, clinical duration, and time to spontaneous recovery of T4/T1 ratio of 0.70 after atracurium or vecuronium injection were measured. No statistically significant differences were found in onset time, but clinical duration and time to recovery were significantly longer in patients receiving tobramycin or gentamicin and paralyzed with vecuronium than for controls (P less than 0.01 for clinical duration and P less than 0.0005 for recovery). The neuromuscular block produced by atracurium was not significantly influenced by the presence of therapeutic serum levels of tobramycin or gentamicin. We conclude that for patients treated with these antibiotics, atracurium may present some advantages over vecuronium when a prolonged block is not desired.     

Antibacterial therapy in patients with malignancies

Summary Patients with malignant disease may be predisposed to bacterial infections because of neoplastic disruption of normal tissue barriers, exogenous immunosuppressive therapy (drugs with or without radiation), and intrinsic host immune deficits secondary to these diseases. Diminished polymorphonuclear leukocyte numbers or function and impaired humoral immunity are highly correlated with the development of serious bacterial infections. The usual signs and symptoms of infection may be absent or altered in a compromised host.Therapy must be instituted promptly upon clinical suspicion of bacterial infection, and empirical choices should usually include combinations that are synergistic for likely pathogens based on knowledge of the local predominant flora and susceptibility data. Synergism has most often been demonstrated in combinations that utilize a -lactam (semisynthetic penicillin or cephalosporin) and an aminoglycoside. Triple drug therapy has not been shown to be advantageous. Monotherapy with third generation cephalosporins, carbapenems, monobactams, or ureidopenicillins has not been proven to offer advantages over 2-drug regimens for these patients.Patients with blood deficient in granulocytes (granulocytopenic) who respond to 2-drug therapy but remain deficient in neutrophils (neutropenic) may need continued treatment until the neutropenia subsides. Those who do not respond and remain febrile with an unclear focus of infection may need to be started on antifungal therapy in addition to the antibacterial agent. The use of oral agents for the prophylaxis of neutropenic patients against bacteremia remains controversial. If drugs are used, co-trimoxazole and nystatin suspension may be preferable.     

硫酸奈替米星注射液与硫酸丁胺卡那注射液临床疗效及安全性的比较

为评价硫酸奈替米星的临床疗效及安全性,在１７０例急性细菌感染性病人中作多中心临床研究。结果显示：硫酸奈替米星的有效率（９５．３％）显著高于对照药硫酸丁胺卡那的有效率（８４．１％）,试验组病人咳痰和腰痛症状的平均下降显著高于对照组;硫酸奈替米星治疗后细菌清除率达９７．２％;２组病人不良反应发生率均为４．８％,对照组中有２例（３．２％）出现耳鸣、１例（１．６％）听力减退,但试验组病人用药后未发现听力异常。结论：硫酸奈替米星临床疗效优于硫酸丁胺卡那且较少耳毒性。     

60株肺炎克雷伯菌多重耐药性及主要耐药基因的研究

目的：了解临床分离的肺炎克雷伯菌耐药性及主要耐药基因存在状况。方法：采用Micmsean微生物鉴定仪，微量肉汤稀释法测定肺炎克雷伯菌对21种抗生素的敏感性。采用聚合酶链反应(PCR)及测序技术分析超广谱B内酰氨酶(ESBLs)，质粒介导的AmpC酶和氨基糖苷类修饰酶基因型。结果：肺炎克雷伯菌对亚胺培南全部敏感，对其他抗生素均有不同程度的耐药。60株全部扩增出TEM基因，有25株检出CTX-M-I群基因，有54株扩增出DHA基因，59株检出共3种氨基糖苷类修饰酶基因。且有22株同时携带2～6种耐药基因。对其中4株细菌进行基因型测序，证实CTX-M-I群扩增产物均为CTX-M-3；DHA扩增产物均为DHA-1；氨基糖苷类修饰酶基因分别为aac(3)-Ⅱ、aac(6′)-I和ant(3″)-I。其中CTX-M-3(AY635141)、DHA-1(AY635140)已注册GenBank(括号内为GenBank注册号)。结论：临床分离的肺炎克雷伯菌为多重耐药菌，同时存在2～6种耐药基因。     

反相离子对高效液相色谱法测定威替米星的稳定性

目的:对威替米星原料药的稳定性进行研究。方法:将威替米星原料药置于不同条件下考察其稳定性,采用反相离子对高效液相色谱法对稳定性放置样品的含量及有关物质进行检测。结果:本品经高温试验[(60.0±s2.0)℃]10d,高湿度试验[相对湿度(75±5)%]10d,加速试验[相对湿度(75±5)%,(40.0±2.0)℃]6mo,长期试验[相对湿度(60±5)%,(25.0±2.0)℃]12mo,原料药的颜色外观略有变化,有关物质及含量均无明显变化,在合格范围之内。但高湿条件下5,10d样品,原料药吸湿严重,含量有所下降。结论:本品在长期放置条件下稳定性良好,但有引湿性,应置于密闭容器、干燥环境中保存。     

微生物法考察威替米星注射液的生物学稳定性

目的:对威替米星注射液的生物学稳定性进行研究。方法:将威替米星注射液置于不同条件下考察其稳定性,采用微生物法和无菌检查法对放置样品的效价稳定性及是否长菌进行检测。结果:本品经高温试验(60.0±s2.0)℃10d,光照试验(4500lx)10d,加速试验[相对湿度(75±5)%,(40.0±2.0)℃]6mo,长期试验[相对湿度(60±5)%,(25.0±2.0)℃]12mo,其效价均未有明显变化,无菌检查亦符合规定。结论:本品在各放置条件下稳定性良好。     

下呼吸道感染患者铜绿假单胞菌分离株氨基糖苷类耐药相关基因分析

目的探讨分离自下呼吸道感染患者的氨基糖苷类耐药铜绿假单胞菌的耐药机制。方法从下呼吸道感染患者痰液中分离出52株对氨基糖苷类耐药的铜绿假单胞菌,PCR法检测6种氨基糖苷类修饰酶(AMEs)基因,并检测其中泛耐药菌的6种16S rRNA甲基化酶基因(以下简称甲基化酶基因)。对阳性产物测序加以证实。结果 52株铜绿假单胞菌中检出4种AMEs基因[aac(3)-Ⅱ、aac(6’)-Ⅰb、aac(6’)-Ⅱ和ant(2″)-Ⅰ],AMEs基因总检出率为92.3%。泛耐药菌中检出1种甲基化酶基因(rmtB)。16株高水平泛耐药菌中rmtB基因的检出率为81.3%。结论分离自下呼吸道感染患者的氨基糖苷类耐药铜绿假单胞菌中AMEs基因携带率高,其对氨基糖苷类耐药与aac(3)-Ⅱ、aac(6’)-Ⅰb、aac(6’)-Ⅱ和ant(2″)-Ⅰ有关;对氨基糖苷类高水平泛耐药主要与甲基化酶基因rmtB有关。     

Trafficking of Systemic Fluorescent Gentamicin into the Cochlea and Hair Cells

Aminoglycosides enter inner ear hair cells across their apical membranes via endocytosis, or through the mechanoelectrical transduction channels in vitro, suggesting that these drugs enter cochlear hair cells from endolymph to exert their cytotoxic effect. We used zebrafish to determine if fluorescently tagged gentamicin (GTTR) also enters hair cells via apically located calcium-sensitive cation channels and the cytotoxicity of GTTR to hair cells. We then examined the serum kinetics of GTTR following systemic injection in mice and which murine cochlear sites preferentially loaded with systemically administered GTTR over time by confocal microscopy. GTTR is taken up by, and is toxic to, wild-type zebrafish neuromast hair cells. Neuromast hair cell uptake of GTTR is attenuated by high concentrations of extracellular calcium or unconjugated gentamicin and is blocked in mariner mutant zebrafish, suggestive of entry via the apical mechanotransduction channel. In murine cochleae, GTTR is preferentially taken up by the stria vascularis compared to the spiral ligament, peaking 3 h after intra-peritoneal injection, following GTTR kinetics in serum. Strial marginal cells display greater intensity of GTTR fluorescence compared to intermediate and basal cells. Immunofluorescent detection of gentamicin in the cochlea also revealed widespread cellular labeling throughout the cochlea, with preferential labeling of marginal cells. Only GTTR fluorescence displayed increasing cytoplasmic intensity with increasing concentration, unlike the cytoplasmic intensity of fluorescence from immunolabeled gentamicin. These data suggest that systemically administered aminoglycosides are trafficked from strial capillaries into marginal cells and clear into endolymph. If so, this will facilitate electrophoretically driven aminoglycoside entry into hair cells from endolymph. Trans-strial trafficking of aminoglycosides from strial capillaries to marginal cells will be dependent on as-yet-unidentified mechanisms that convey these drugs across the intra-strial electrical barrier and into marginal cells.     

Gentamicin and sisomicin — Induced renal tubular damage

Summary Early signs of aminoglycoside — induced renal tubular damage were detected in 26 patients given gentamicin and 23 given sisomicin. The urinary elimination of 3 low molecular weight proteins (LMWP) — beta 2 microglobulin, retinol binding protein and lysozyme (LZM), and the urinary activity of 2 enzymes — alanine aminopeptidase and N-acetylbeta-glucosaminidase — was measured before, during and after treatment. In gentamicin — treated patients LMWP elimination increased, especially LZM which rose markedly during treatment and returned to normal values after its end. Enzyme activities also rose while gentamicin was being given. Sisomicin produced smaller changes. As neither the mean serum creatinine nor the mean urinary elimination of transferrin were increased, glomerular function was probably not affected. However, tubular damage was detected, as shown by the LMWP output (especially LZM) and increased enzyme activity. Urinary LMWP and enzyme measurements are presented as sensitive and reliable methods to monitor early aminoglycoside — induced tubular impairment. It is suggested that the different renal toxicities of gentamicin and sisomicin are related to differences in their accumulation in the renal cortex.