Macrolides allergy

Macrolides are characterised by their basic structure which is made up of a lactonic cycle with 2 osidic chains. They are classified according to the number of carbon atoms in the cycle : 14 membered macrolides (erythromicin, roxithromycin, dirithromycin, clarithromycin), 15 membered (azithromycin) and 16 membered (spiramycin, josamycin, midecamycin) macrolides. Epidemiological studies show that macrolides are amongst the safest antibiotics, but in these series, no drug allergy work up was performed. An immediate IgE dependent hypersensitivity has been shown with erythromycin in some cases. The mechanism is unknown and the skin tests are negative in most other cases. It would appear that the macrolide allergies are unlikely to be class allergies. Eviction is the treatment of choice. Desensitization has been successful in a few cases.     

Macrolides: pharmacokinetics and pharmacodynamics

Three pharmacokinetic/pharmacodynamic parameters--(i) the peak concentration to the minimum inhibitory concentration ratio (C(max)/MIC); (ii) the area under the concentration-time curve to MIC ratio (AUC(24h)/MIC); and (iii) the time the concentration exceeds the MIC (T>MIC)--are important predictors of the clinical efficacy of antibiotics. For antibiotics with pronounced concentration-dependent killing, such as the fluoroquinolones or the aminoglycosides, C(max)/MIC and AUC(24)/MIC are the main factors that establish efficacy. Antibiotics with a weak, or no, concentration dependency generally have their efficacy linked to T>MIC, and these include the beta-lactams and the conventional macrolides. Antibiotics with weak concentration-dependent effects, but with prolonged persistent effects, such as tetracyclines and azithromycin, have their activity mostly related to the AUC(24)/MIC. By applying these concepts to current antibiotics, and also to the development of novel agents, it is possible to optimise their dosages and administration schedules. This will maximise therapeutic efficacy, may prevent or delay the emergence of bacterial resistance to antibiotics, and can certainly minimise side-effects.     

Macrolides and changes in the oral flora

Macrolides have been used in dental practice for many years, and may have a role in treating periodontal disease. Increased numbers of antibiotic-resistant oral streptococci have been reported after administration of both penicillins and macrolides. We confirm these findings for erythromycin, josamycin and azithromycin, and show that small numbers of macrolide-resistant streptococci are part of the normal oral flora at baseline. Resistant organisms fill the vacuum created by the removal of sensitive strains by antibiotic treatment. Following treatment with azithromycin, periodontal bacterial pathogens such as black pigmented anaerobes and spirochaetes decrease, whereas numbers of oral streptococci increase. These changes in the oral flora indicate a return to a healthier oral environment. In our studies, no clinical problems resulted from the transient increase in macrolide-resistant streptococci.     

Macrolides: structures and microbial targets

The macrolide class of antibiotics is well established and often recommended for use in the treatment of community-acquired respiratory tract infections. A number of agents with varying antimicrobial activity have been developed via chemical modification of the core macrolide structure, a macrocyclic lactam ring. Although structurally diverse, the macrolides share a common ability to bind to the bacterial 50S ribosome subunit and inhibit protein synthesis, thereby preventing bacterial multiplication. Resistance in the clinic is due to modification of the 50S subunit in the area of the peptidyl transferase center or to an efflux pump. The newer macrolides, and in particular azithromycin, with their broad-spectrum microbiological profile have extended the therapeutic uses of this class of antibiotics and ensured that they remain an integral part of the clinician's armamentarium.     

对大环内酯类药物的新认识

大环内酯类药物(macrolide antibiotic,MA,以下简称MA)被广泛应用于临床.近年来有较多关于其非抗菌作用的报道,已引起医药研究者的广泛关注.这些作用的发现拓宽了MA的应用范围,人们对其有了新的认识.本文就MA的临床应用进展进行综述.     

酿脓链球菌对大环内酯类抗菌药物耐药表型与基因型研究

目的 研究酿脓链球菌对大环内酯类抗菌药物的耐药表型与基因型。方法 采用琼脂平板稀释法测定97株酿脓链球菌对红霉素、克林霉素、麦迪霉素、阿奇霉素、克拉霉素和青霉素的敏感性；用双纸片法检测酿脓链球菌耐药表型；用PCR方法检测耐大环内酯的酿脓链球菌携带的耐药基因。结果 97株酿脓链球菌中82株表现为对大环内酯类抗菌药物不敏感，其中42株表现为eMLS型耐药，37株为iMLS型耐药，3株细菌为主动外排M型耐药；82株对大环内酯不敏感的酿脓链球菌中77株检测到耐药基因，其中12株具有ermB基因，25株具有ermTR基因，2株具有mefA基因，21株同时具有ermB／ermTR基因，5株同时具有ermB／mefA基因，3株同时具有ermTR／mefA基因，9株同时具有ermB／ermTR／mefA基因，5株未能检测到三种耐药基因。结论 酿脓链球菌对大环内酯类抗菌药物的耐药率较高，耐药表型以cMLS和iMLS为主，耐药基因以ermB和ermTR多见。     

第2代大环内酯类抗生素的临床应用评价

目的:阐述第2代大环内酯类抗生素的研究进展和临床应用评价.方法:采用近期国内外相关文献进行综述.结果:第2代大环内酯抗生素研究进展迅速,其抗菌谱更趋广泛,对需氧菌和厌氧菌的抗菌能力较第1代的红霉素均有所增强.结论:第2代大环内酯类具有血浆半衰期长、良好的耐受性和药代动力学性质,在临床对抗感染性疾病和非感染性疾病上显示出良好的效果.     

大环内酯类抗生素的快速系统鉴别方法

大环内酯类抗生素是一类广谱抗菌药物,临床应用广泛.由于同一官能团在同系化合物中的反应相同,按现行药品标准对其制剂进行鉴别难以区分,因此,被假冒的频率较高.由于我国假药集散地又多在基层,取证样品量较小,受仪器设备和实验条件的限制,在打假工作中靶向性差.我们对大环内酯类抗生素进行了快速系统鉴别方法的研究,建立了以颜色反应与薄层色谱相结合的大环内酯类抗生素快速系统鉴别方法.该方法具有使用设备简单,样品消耗量小,检出速度快,结果准确度高,安全性好的特点,尤为适合于基层现场打假工作的需要.     

大环内酯类抗生素薄层色谱鉴别

采用硅胶H-CMC-Na薄层色谱板;展开剂选择苯—无水甲醇—吡啶(13:2:1);显色剂为碘蒸气。对麦白霉素、柱晶白霉素和乙酰螺旋霉素等大环内酯类抗生素薄层色谱鉴定,方法灵敏、稳定、重现性良好。     

大环内酯类抗生素的临床应用进展

大环内酯类抗生素在临床上应用非常广泛,不仅可用于细菌、非典型痛原体、分枝杆菌所致的呼吸系统、泌尿生殖系统、皮肤软组织等感染性疾病,且对某些非感染性疾病如弥漫性泛细支气管炎、特发性肺纤维化、支气管哮喘、胃肠动力障碍性疾病、幽门螺杆菌(Hp)的根除及动脉粥样硬化也有较好的作用.     

第2代大环内酯类抗生素的进展

目的：阐述第2代大环内酯类抗生素的作用特点和临床应用进展。方法：采用中外献综述。结果：第2代大环内酯类抗生素的抗菌谱更趋广泛，对需氧菌和厌氧菌的抗菌能力较第1代的红霉素均有所增强。结论：第2代大环内酯类抗生素的抗菌语广、杀菌力强、血浆半衰期长，同时毒副作用较小，对临床各种感染显示良好的效果。     

前置胎盘、胎盘粘连、胎盘植入与人工流产的关系

目的探讨前置胎盘、胎盘植入、胎盘粘连与人工流产的关系。方法对在本院分娩的4010例患者进行回顾性分析。结果 4010例分娩患者中,胎盘粘连、胎盘植入、前置胎盘发病率为10.3%（414/4010）,1628例无人工流产史者中,总发病率为3.6%,2382例有人工流产史者总发病率为14.9%,差异有统计学意义（P〈0.05）。随着人工流产次数的增加,胎盘粘连、胎盘植入、前置胎盘发病率呈明显上升趋势（P〈0.05）,胎盘粘连发病率最高。产后出血发生率为66.9%,胎盘植入者产后出血发生率最高。结论前置胎盘、胎盘植入、胎盘粘连发病率与人工流产次数成正比,均易导致产后出血。     

Desmethyl Macrolides: Synthesis and Evaluation of 4,10-Didesmethyl Telithromycin

Novel sources of antibiotics are required to keep pace with the inevitable onset of bacterial resistance. Continuing with our macrolide desmethylation strategy as a source of new antibiotics, we report the total synthesis, molecular modeling and biological evaluation of 4,10-didesmethyl telithromycin (4), a novel desmethyl analogue of the 3rd-generation drug telithromycin (2). Telithromycin is an FDA-approved ketolide antibiotic derived from erythromycin (1). We found 4,10-didesmethyl telithromycin (4) to be four times more active than previously prepared 4,8,10-tridesmethyl congener (3) in MIC assays. While less potent than telithromycin (2), the inclusion of the C-8 methyl group has improved biological activity suggesting it plays an important role in antibiotic function.     

医院卫生技术评估在大环内酯类抗菌药物遴选评价中的应用

目的 贯彻落实河北省卫生健康委《河北省公立医疗机构用药目录遴选评价管理指南》的要求,为医院决策者遴选、临床合理使用大环内酯类抗菌药物提供循证依据.方法 依照百分制评分体系,参考药品说明书、临床指南和文献,从安全性、有效性、经济性、创新性、适宜性和可及性等6个方面分别对河北省人民医院口服大环内酯类抗菌药物进行医院卫生技术...     

Macrolides as immunomodulatory medications for the therapy of chronic lung diseases

Macrolide antibiotics have potent immunomodulatory activity. The spectrum of action of these antibiotics extends to regulation of leukocyte function and production of inflammatory mediators, control of mucus hypersecretion, resolution of inflammation, and modulation of host defense mechanisms. Macrolides are now being used or investigated to treat chronic lung inflammatory diseases, including diffuse panbronchiolitis (DPB), cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) and asthma. Intense research is ongoing to further elucidate the targets and mechanism/s of action of macrolides in eukaryotic cells. In this paper, we review recent findings on novel effects of macrolides on epithelial barrier function and resolution of inflammation, which may shed light on the mechanisms underlying the beneficial effects of macrolides in the clinic.     

Macrolides beyond the conventional antimicrobials: a class of potent immunomodulators

The historical change in the natural course of diffuse panbronchiolitis (DPB), a fatal disorder of the airways, following the introduction of erythromycin in its treatment has focused attention of researchers on the anti-inflammatory properties of macrolides. Chronic inflammation of the airways accompanied by infiltration by neutrophils and overproduction of mucus and pro-inflammatory cytokines is observed in bronchial asthma, cystic fibrosis (CF), DPB, chronic obstructive pulmonary disease (COPD) and bronchiectasis. The airways of these patients are often colonised by mucoid Pseudomonas aeruginosa attached to epithelium by a biofilm. Bacteria intercommunicate for biofilm formation by a system of lactones known as quorum sensing. Macrolides inhibit mobility and quorum sensing of P. aeruginosa; they also decrease production of mucus by epithelial cells and biosynthesis of pro-inflammatory cytokines from monocytes and epithelial cells by inhibiting nuclear factor-kappaB. Large, randomised clinical trials for the management of these disorders with macrolides are not available, with the sole exception of four trials denoting benefit following long-term administration of azithromycin in patients with CF. That benefit is consistent with an increase in forced expiratory volume in 1s (FEV(1)) and a decrease in the rate of bacterial exacerbations. Studies with small numbers of patients with COPD revealed attenuation of the inflammatory reaction by macrolides. Experimental studies of Gram-negative sepsis have shown considerable attenuation of the systemic inflammatory response following intravenous administration of clarithromycin. Results of the effects of clarithromycin in patients with ventilator-associated pneumonia and sepsis in a large, randomised study of 200 patients are awaited.     

The Therapeutic Role of Macrolides and Ketolides: Not Just Antibacterials

The 6th International Conference on Macrolides, Azalides, Streptogramins, Oxazolidinones and Ketolides was held this year in Bologna, Italy, January 24-25, 2002. While oxazolidinones were featured in only one presentation, there were many presentations on the azalide azithromycin. There were also presentations on other macrolides (clarithromycin) and ketolides (telithromycin and ABT-773), and a few presentations on streptogramins. Several stimulating and well-attended workshops, as well as special symposia, made it an interesting and worthwhile meeting. (c) 2002 Prous Science. All rights reserved.