反相离子对高效液相色谱法测定威替米星及其有关物质的含量

目的:建立一种用于分析新的氨基糖苷类抗生素———威替米星的反相离子对高效液相色谱法。方法:直接采用紫外检测器检测威替米星及其有关物质。在AgilentXDBC8柱上威替米星和有关物质达到完全分离,柱温为30°C,流动相为乙腈∶缓冲液(20mmol·L-1庚烷磺酸钠,30mmol·L-1三乙胺,加磷酸调pH至2.5)(25∶75)。结果:方法评价结果显示本法具有良好的线性和重现性。威替米星的最低检测限为0.1μg。结论:本研究建立的方法可以用于测定原料药和注射液中威替米星的含量和有关物质检查。     

磷霉素与氨基糖苷类药物联合应用的研究进展

磷霉素不同于任何其他抗菌药物，具有独特化学结构与抗菌机制，与一些抗菌药物联用呈现协同作用；氨基糖苷类药物抗菌谱广、杀菌活性强，但耳、肾毒性限制了其临床应用。本文拟通过药效学特性、药物安全性以及细菌生物被膜3部分内容，综述磷霉素与氨基糖苷类药物联合应用的研究进展，以期为临床联合用药提供参考，促进临床安全合理用药。     

磷霉素与五种氨基糖苷类抗菌药物对20株铜绿假单胞菌的联合药敏研究

目的:评价磷霉素分别与五种氨基糖苷类抗菌药物(阿米卡星,异帕米星,庆大霉素,奈替霉素,妥布霉素)对20株临床分离铜绿假单胞菌的体外联合抗菌效应。方法:采用棋盘法设计,微量肉汤稀释法测定。测定不同浓度组合的5组抗菌药物对20株临床分离的铜绿假单胞菌的最低抑菌浓度,并计算FIC指数判定联合效应。FIC≤0.5为协同作用,0.52为拮抗作用。结果:磷霉素与5种氨基糖苷类药物联合应用后,药物MIC50显著降低。FIC指数分布:FIC≤0.5占65%～85%;0.52为0。结论:磷霉素与氨基糖苷类抗菌药物联合用药后,对铜绿假单胞菌表现为协同作用和相加作用,并以协同作用为主,无关作用较少,更无拮抗作用。     

Topical gentamicin and ethacrynic acid: Effects on cochlear function

Objective: To determine whether concurrent intravenous administration of the loop diuretic ethacrynic acid potentiates the toxicity of the aminoglycoside antibiotic gentamicin applied topically on the round window. Study Design: The authors studied the effects on cochlear sensitivity of co-administered intracardiac ethacrynic acid (40 mg/kg) and high-dose topical gentamicin solution (100%) applied to the round window. Comparisons were made with animals receiving ethacrynic acid plus systemic gentamicin (100 mg/kg); topical gentamicin alone; systemic gentamicin alone; and intravenous ethacrynic acid alone. Methods: Experiments were carried out on pigmented guinea pigs weighing 400 to 500 g. Changes in cochlear function were characterized by monitoring shifts in compound action potential (CAP) thresholds by use of chronic indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. Results: After 20 days animals receiving ethacrynic acid in combination with topical gentamicin to the round window failed to demonstrate a significant deterioration in cochlear sensitivity, whereas all animals receiving systemic gentamicin plus ethacrynic acid experienced profound increases in CAP thresholds. Conclusions: This study supports the contention that ethacrynic acid potentiates aminoglycoside ototoxicity by facilitating the entry of the antibiotics from the systemic circulation into the endolymph. In addition, this study answers important clinical concerns regarding the safety of the use of topical aminoglycoside agents in combination with loop diuretics.     

Antibiotic Treatment of Staphylococcus aureus Endocarditis

ABSTRACT Clinical and bacteriological information of Staphylococcus aureus endocarditis was reviewed in 119 cases from all over Denmark. Overall mortality was 71%. Survival correlated with anti-staphylococcal treatment, short duration from onset of infection to start of treatment, and long duration of treatment. In spite of relevant treatment, mortality was significantly lower in cases infected with penicillin-susceptible strains than when penicillin-resistant strains were isolated. There were no differences in the effect of various anti-staphylococcal treatment regimens; in particular, there were no differences in mortality with regard to beta-lactam antibiotics alone as compared to beta-lactam antibiotics in combination with aminoglycosides. However, embolic manifestations occurred more often after start of treatment with combination therapy than with beta-lactam antibiotics alone.     

Aminoglycosides in cystic fibrosis: a descriptive study of current practice in Australia

Aim: To determine the diversity of clinical practice with respect to aminoglycosides in cystic fibrosis (CF) units within Australia. Method: In April 1999, a questionnaire on the use of aminoglycosides was sent to 30 CF units across Australia. Information was collected about drug selection, dosing, monitoring and toxicity with intravenous administration. Results: Completed surveys were received from 26 of the 30 units (response rate = 86%) and all units with > 40 patients. Tobramycin was the drug of choice in all but two centres where there was equivalent use of gentamicin and tobramycin. The survey demonstrated a trend in recent years to reduce the number of doses per day with 54% of centres prescribing once daily, 23% twice daily and 23% thrice daily regimens. Initial dosing was generally based on mg/kg per day (mean 8.8, range 7.5–10 mg/kg per day). Dosing by infusion occurred in 11 of 14 units using once‐daily dosing and there was equivalent use of bolus and infusion methods for multiple‐daily regimens. Drug monitoring depended on dosing regimen. Units using multiple daily regimens monitored using trough ± peak levels, whereas 50% of units using once‐daily dosing used two postdose levels to alter dose. Actual toxicity, in particular nephrotoxicity, ototoxicity and vestibular toxicity was reported by 19, 27 and 12% of units, respectively. Conclusion: The prescribing, dosing and monitoring of aminoglycosides in CF across Australia varies greatly. This is likely to be due to a lack of definitive evidence as to the optimum use in this patient group. (Intern Med J 2001; 31: 23–26)     

In vitro activity of twenty-three antimicrobials againstYersinia pestis strains

The microdilution method was used to determine the MICs of twenty-three antimicrobials against the 22 strains ofYersinia pestis that have been stocked in the National Institute of Health, Japan. The three fluoroquinolones, ofloxacin, ciprofloxacin and sparfloxacin, were most active, with MIC_90S of 0.125 μg/ml. The cephems showed considerable differences in activity: cefdinir and cefotaxime were the most active of this group, with MIC_90S of 0.25 μg/ml; they were followed by cefminox and latamoxef with MIC_90S of 0.5 μg/ml. The two carbapenems tested, imipenem and panipenem, were potently active at MIC_90S of 0.5 μg/ml. The study obtained MIC_90S for tetracycline and doxycycline ranging from 1.0 to 2.0 μg/ml, even though these drugs are known to be clinciall active against plague. Erythromycin and clarithromycin were the least active agents.     

Intracellular readthrough of nonsense mutations by aminoglycosides in coagulation factor VII

BACKGROUND: Nonsense mutations in coagulation factor (F) VII potentially cause a lethal hemorrhagic diathesis. Readthrough of nonsense mutations by aminoglycosides has been studied in a few human disease models with variable results. OBJECTIVES: We investigated the K316X and W364X FVII mutations, associated with intracranial hemorrhage, and their correction by aminoglycosides. The rare nonsense mutations in FVII represent favorite models to test this strategy, because even tiny increases in the amount of functional full-length protein in patients could ameliorate hemorrhagic phenotypes. RESULTS: A FVII-green fluorescent protein (GFP) chimaera provided us with a fluorescent model of FVII expression in living cells. Appreciable fluorescence in cells transfected with nonsense FVII-GFP mutants was detected upon geneticin treatment, thus demonstrating suppression of premature translation termination. To investigate the rescue of FVII function, nonsense variants of the native FVII without GFP (p316X-FVII and p364X-FVII) were transfected and found to secrete low amounts of FVII (approximately 1% of Wt-FVII activity), thus suggesting a spontaneous stop codon readthrough. Geneticin treatment of cells resulted in a significant and dose-dependent increase of secreted FVII molecules (p316X-FVII, 24 +/- 12 ng mL(-1), 3.6 +/- 0.8% of Wt-FVII activity; p364X-FVII, 26 +/- 10 ng mL(-1), 3.7+/-0.6%) characterized by reduced specific activity, thus indicating the synthesis of dysfunctional proteins. Similar results were observed with gentamicin, a commonly used aminoglycoside of potential interest for patient treatment. CONCLUSIONS: Our approach, extendable to other coagulation factors, represents an effective tool for a systematic study of the effects of aminoglycosides and neighboring sequences on nonsense codon readthrough. These results provide the rationale for a mutation-specific therapeutic approach in FVII deficiency.     

Contact allergy to neomycin sulfate: results of a multifactorial analysis

PURPOSE: To perform a comprehensive, multifactorial analysis of potential risk factors (demographic and clinical) for contact allergy to neomycin sulfate, a common adverse reaction resulting from the topical use of this drug; especially in some subgroups of the population. METHODS: Retrospective analysis of allergy test data of the Information Network of Departments of Dermatology (IVDK, www.ivdk.org) between 1998 and 2003, including all patients patch tested with a standard screening series because of suspected allergic contact dermatitis (ACD). As one outcome, a positive (allergic) test reaction to neomycin sulfate was considered. An alternative outcome included only those patients with a positive test to neomycin sulfate and a final diagnosis of ACD. The association between outcome and potential risk factors was analyzed with Poisson regression analysis, deriving prevalence ratios (PR) as risk estimates. RESULTS: Of the 47,559 patients tested, 2.5% had positive reactions to neomycin sulfate, while in 1.1% ACD was additionally diagnosed. The results of the multifactorial analysis indicated that the risk of both outcomes decreased slightly during the period covered; was higher among patients with leg dermatitis; varied significantly with age and increased progressively with the number of additional positive reactions to other standard series allergens. Cross-reactivity to other, selectively tested, aminoglycoside antibiotics was substantial (kappa = 0.67; 95%CI: 0.63-0.71) for framycetin sulfate, to low (kappa = 0.33; 95%CI: 0.27-0.37) for gentamicin sulfate. CONCLUSIONS: The prevalence of contact sensitization to neomycin sulfate was noteworthy among patients patch tested in the IVDK centers. Supplementing clinical epidemiology, neomycin contact allergy has been estimated to be relatively common even on the level of the unselected population (prevalence approx. 1%). Hence, the topical use of neomycin sulfate by patients should be carefully monitored, considering its potential to induce ACD, with emphasis on subgroups at risk.     

1230例抗生素不良反应分析

目的 :探讨抗生素不良反应的规律及特点 ,指导合理用药。方法 :用文献计量学方法对近10年国内公开报道的1230例抗生素所致的不良反应进行分析。结果 :1230例抗生素不良反应占同期药物不良反应的46 19 % (1230/2663) ,品种以β-内酰胺类居首 (18种 ) ,例次数氨苄青霉素最多 (192例 ) ,其表现累计例次最多的是皮肤及其附件损害 (691例 ) ,最严重的是过敏性休克 (109例 ) ,其中 β-内酰胺类占76 15 % (83/109) ,氨基糖苷类的肾损害占本文全部肾损害的51 79 % (29/56) ,不容忽视。结论 :审慎用药 ,抗生素不良反应是可以大大减少的