替加环素治疗ICU广泛耐药鲍曼不动杆菌感染临床分析

摘 要 目的:回顾性分析替加环素治疗广泛耐药鲍曼不动杆菌(XDRAB)的微生物学清除率及临床治疗效果。方法：选择我院重症医学科2013～2014年29例确诊为XDRAB感染并单用或联合使用替加环素治疗的患者的病历资料。替加环素首剂100 mg,随后每12 h 50 mg ivd,疗程≥3 d,收集其临床及微生物学相关资料。结果：29例XDRAB感染患者应用替加环素治疗后,11例(37.9%)临床治疗有效,8例(27.6%)微生物清除。10例(34.5%)因临床和细菌学反应差而在2周内死亡。替加环素联合头孢哌酮/舒巴坦的临床有效率75%,优于其他方案。结论：替加环素联合头孢哌酮/舒巴坦治疗XDRAB感染效果较好。     

替加环素治疗心脏外科术后泛耐药鲍曼不动杆菌感染的回顾性病例分析

摘要：目的:了解替加环素(200 mg·d-1)在心脏外科术后泛耐药鲍曼不动杆菌（XDRAB）感染中的使用情况。方法:调取2017年1月～2019年12月医院心脏大血管外科监护病房使用替加环素的病例,对感染部位、致病菌及药敏情况,以及替加环素给药方案、临床疗效、不良反应等进行回顾性分析。结果:收集到相关病例共50例,其中肺部感染46例,血流感染4例。治疗方案分别为替加环素联合含舒巴坦制剂（36例）和替加环素联合碳青霉烯类药物（14例）。50例患者的临床有效率为60.0%（30/50）,细菌清除率为46.0%（23/50）;替加环素+含舒巴坦制剂组临床有效率和细菌清除率均优于替加环素+碳青霉烯组（P<0.05）。共发生替加环素相关不良反应10例,包括肝功能损害5例,以胆汁淤积型为主,其次是血清淀粉酶和脂肪酶升高（2例）、凝血功能障碍（2例）和胰腺炎1例。结论:治疗心脏外科手术后XDRAB感染,替加环素(200 mg·d-1)联合含舒巴坦制剂方案有效性优于联合碳青霉烯方案;替加环素不良反应发生率较高,临床应高度警惕肝功能异常、凝血功能异常、胰腺炎等不良反应的发生。     

北京地区2013～2018年替加环素不良反应回顾性分析

摘 要 目的：了解替加环素不良反应发生的特点,为临床安全使用替加环素提供参考。 方法：调取国家药品不良反应（ADR）监测系统收集的2013～2018 年北京地区替加环素ADR报告,对其发生的特点及相关因素进行回顾性分析。 结果：统计时间内,共收到49份怀疑与替加环素有关的ADR报告。其中60岁以上老年患者居多,占67.35％;临床表现复杂多样,主要ADR累及系统为血液系统（36.21%）、消化系统（20.69%）、皮肤软组织及附件（17.24%）。ADR发生在2～6 d内占40.82％,大多经停药或对症治疗后好转。 结论：临床合理使用替加环素可以减少其ADR 的发生。建议在使用该药时,对患者进行严密监护,以降低发生ADR的风险。     

132例患者使用替加环素的用药合理性分析

摘 要 目的：评价临床使用替加环素的合理性,为加强替加环素使用的规范化管理,促进合理用药提供依据和参考。方法: 采用回顾性研究方法,抽取我院2014~2016年出院患者病历,收集使用替加环素的病历132份,对患者的性别、年龄、疾病类型、感染部位、病原学检查、替加环素用法用量、给药疗程、联合用药、临床疗效以及用药合理性、不良反应等方面进行统计分析。结果: 我院近3年来使用替加环素抗感染治疗的患者病原学送检率86.37%,临床有效率81.82%,替加环素合理使用率63.64%,基本合理使用率13.64%,不合理使用率为22.72%,药品不良反应发生例数较多,达20例（15.15%）。结论: 医疗机构对替加环素的使用必须严格管理,并对其适应证、给药方案、不良反应和处方权加以控制,减少经验性用药,提高合理用药水平。     

6例替加环素相关性低血糖不良反应文献分析

摘 要 目的：分析替加环素相关性低血糖不良反应病例及其临床特点,为临床安全用药提供参考。方法：通过检索Medline、PubMed、Springer数据库,中国学术期刊全文数据库（CNKI）和维普中文科技期刊数据库（VIP）,收集替加环素相关性低血糖的不良反应个例报道,并对患者性别、年龄、合并基础疾病、联合用药以及低血糖发生时间、临床表现及预后等进行统计分析。结果：收集整理了6例患者使用替加环素50 mg维持剂量后发生低血糖反应,期间分别合并使用了降糖药、降压药、调血脂药等。低血糖不良反应主要发生在用药后1周内,很可能为替加环素相关性低血糖,且不良反应严重。结论：替加环素相关性低血糖的不良反应较少,但后果严重,应引起临床的重视,尤其是既往有糖尿病的老年患者合并用药时,如必须使用应加强血糖等用药监护,早期发现不良反应并给予对症治疗。     

替加环素致1例凝血功能障碍

1例42岁男性患者,因重症中暑继发肺部感染,先后给予头孢西丁、哌拉西林他唑巴坦、头孢哌酮舒巴坦、万古霉素抗感染。治疗第24天,加用替加环素后患者出现凝血功能异常,第33天,考虑凝血功能障碍可能与替加环素相关,停药3 d后凝血功能恢复正常。     

注射用替加环素临床前安全性研究

目的 评价注射用替加环素的安全性。方法 对注射用替加环素进行血管刺激、肌肉刺激、溶血性及被动皮肤过敏、全身主动过敏性、类过敏性试验。结果 注射用替加环素对血管无明显刺激性、对肌肉组织产生轻度可逆性的刺激,对家兔红细胞无溶血、凝聚作用,大鼠被动皮肤过敏反应（PCA）试验未出现过敏反应;豚鼠全身主动过敏反应（ASA）试验部分豚鼠出现过敏反应;注射用替加环素与已上市药品Tygacil 在同等剂量下,豚鼠出现同等程度的类过敏反应。结论 注射用替加环素可能会引起肌肉刺激性及过敏、类过敏反应,临床应用时应关注患者给药后的反应。     

替加环素治疗耐碳青霉烯类鲍曼不动杆菌肺炎疗效的回顾性研究

摘 要 目的：分析替加环素治疗耐碳青霉烯类鲍曼不动杆菌（CRAB）所致医院获得性肺炎（HAP）的疗效及影响因素。方法：采用回顾性研究方法,收集2015年1月～2017年6月在解放军第458医院接受过替加环素治疗的CRAB所致HAP患者资料,评定其临床疗效和微生物学疗效,对临床治愈和无效患者的基线资料和疗效指标进行比较分析,以Logistic回归分析统计替加环素疗效的独立影响因素。结果：共纳入128例患者,其中临床治愈80例,无效48例,治愈率62.5%。95.0%的治愈患者为联合治疗。无效组患者的治疗前WBC计数明显高于治愈组（P＜0.05）;接受替加环素治疗前抗菌药使用时间无效组明显长于治愈组（P＜0.05）。Logistic回归分析显示,APACHE Ⅱ评分高的患者治愈的概率是评分低患者的0.699倍（P＜0.05）。结论：替加环素治疗耐碳青霉烯类鲍曼不动杆菌所致医院获得性肺炎具有较好疗效,患者APACHE Ⅱ评分可能是替加环素疗效的独立影响因素。     

替加环素致多重耐药菌感染患者低纤维蛋白原血症的药学监护

目的 为临床治疗多重耐药菌感染患者使用替加环素致低纤维蛋白原血症的药学监护和替加环素的安全使用提供参考。方法 临床药师通过参与1例多重耐药菌感染患者使用替加环素致低纤维蛋白原血症的案例，对替加环素与低纤维蛋白原血症不良反应的相关性进行判断，并结合相关文献分析替加环素致低纤维蛋白原血症发生的危险因素和可能机制；建议医师停用替加环素，并给予人纤维蛋白原和血浆纠正。结果与结论 替加环素与患者的低纤维蛋白原血症有关。医师采纳临床药师意见，患者纤维蛋白原水平恢复至正常水平。替加环素致低纤维蛋白原血症发生的危险因素包括大剂量、长疗程用药，以及患者自身合并肾功能不全。临床药师及时给予医师停药建议，并建议在必要时输注人纤维蛋白原和血液制品进行纠正，避免了严重且危及生命的凝血障碍的发生，保障了替加环素使用的安全性。     

替加环素致凝血功能障碍文献分析

目的:分析替加环素致凝血功能障碍的发生规律及特点,为临床安全用药提供参考.方法:检索中国学术期刊全文数据库、维普中文科技期刊数据库、PubMed、Embase及SCI数据库收载的替加环素致凝血功能障碍的个案报道,进行分析.结果:共检索到替加环素致凝血功能障碍病例17例,男性12例,女性5例,其中合并肝功能异常的患者5例...     

替加环素导致凝血系统不良反应的危险因素及可能机制研究进展

替加环素是一种具有广泛抗菌活性的甘氨酰环素类抗菌药物,因其耐药率低、抗菌活性强,临床使用量逐年增加。近年来,伴随着使用量的增加其安全性争议也越来越多,关于凝血系统的不良反应报道明显增多,研究报道相关危险因素也不尽相同。因此,本文综述了替加环素引起的凝血系统不良反应及其危险因素。替加环素用药期间可出现纤维蛋白原降低、活化部分凝血活酶时间、凝血酶原时间和凝血酶时间延长等凝血参数的改变,长疗程使用替加环素、用药前低纤维蛋白原值、腹部感染、高龄和肾功能损伤可能是替加环素相关凝血异常的危险因素。     

替加环素相关急性胰腺炎

替加环素(tigecycline)是一种新型广谱抗生素,为甘氨酰环素类(glycyclines)抗生素的首个药物,其化学结构与四环素相似.替加环素对革兰阳性菌和革兰阴性菌具有抗菌活性,用于治疗复杂皮肤、软组织感染和复杂腹腔内感染.通常,替加环素偶致急性胰腺炎,但近年资料表明,替加环素致急性胰腺炎有所增加.临床表现主要为恶心、呕吐、腹痛、腹胀以及血清脂肪酶和淀粉酶水平升高.替加环素致胰腺炎的机制尚不明确,但由于替加环素的结构与四环素结构相似,推测替加环素是通过四环素致胰腺炎的同样机制引起急性胰腺炎.替加环素若引起胰腺炎,应立即停药,保持患者禁食状态,静脉给予足量液体,并给予其他对症治疗.替加环素使用期间,临床医师应密切观察患者有无胰腺炎的症状和体征,监测患者的血清脂肪酶和淀粉酶水平.     

替加环素治疗对重症患者凝血功能的影响

目的:研究重症患者静脉使用替加环素对凝血功能的影响。方法:采用回顾性研究方法,提取2017年1月至2018年6月某院ICU使用替加环素静脉治疗的重症患者数据,按照替加环素剂量分为低剂量组和高剂量组,测定患者用药前、用药过程中、停药后的凝血指标。收集患者年龄、感染部位、肝肾功能情况、病原学培养结果等指标并分析。结果:替加环素可显著延长PT、APTT及TT,显著降低FBG、PLT水平(P=0.015、0.027、0.001、0.003、0),高剂量组APTT(P=0.024)、死亡率、出血率、输血率均高于低剂量组。替加环素剂量、用药前基础凝血功能水平可显著影响用药疗程中的凝血功能(P<0.05)。结论:替加环素可显著影响患者凝血功能,可能增加出血风险,使用时需监测患者凝血功能变化。     

替加环素致低纤维蛋白原血症的危险因素和可能机制

替加环素为广谱抗菌药物,具有耐受性良好、安全有效等特点。随着临床的广泛应用,替加环素相关的、危及生命的低纤维蛋白原血症个案报道逐渐增多,仍缺乏系统性临床研究。本文综述了替加环素在治疗中出现低纤维蛋白原血症的危险因素和潜在机制,为临床合理应用提供一定的参考。     

Development mechanism of resistant population post-exposure to tigecycline in tigecycline-heteroresistant Acinetobacter baumannii strain

Tigecycline heteroresistance is highly prevalent in Acinetobacter baumannii clinical isolates, reducing the efficacy of tigecycline treatment. This study investigated the population dynamics of A. baumannii with tigecycline heteroresistance to determine the origin of resistance that occurs over time after antibiotic exposure. Tigecycline heteroresistance was imitated by mixing tigecycline-susceptible and -resistant A. baumannii isolates in a 1:10^?6 ratio, and confirmed using population analysis profiling. Growth curves and an in-vitro competition assay found no difference in bacterial fitness between tigecycline-resistant and -susceptible populations. The green fluorescent protein (GFP) expression system and flow cytometry were used to monitor the population dynamics of the heteroresistant population, while differentiating the resistant population from the susceptible population. The mimicked tigecycline heteroresistance was confirmed to be reproducible and stable without tigecycline. The GFP-expressing population (i.e. the resistant population) nearly went undetected because it only represented approximately 10^?6 of the entire population. However, when the mimicked tigecycline-heteroresistant strain was treated with tigecycline, most subpopulations expressing GFP were detected. The surviving A. baumannii population, upon exposure to tigecycline, exhibited a high minimum inhibitory concentration for tigecycline, equivalent to that of tigecycline-resistant isolates that were used to mimic heteroresistance. These results indicate that the development of resistance in tigecycline-heteroresistant A. baumannii strains, resulting in decreased antibiotic efficacy, may depend on the selection of a pre-existing resistant subpopulation.     

Efficacy of tigecycline and vancomycin in experimental catheter-related Staphylococcus epidermidis infection: microbiological and electron microscopic analysis of biofilm

Central venous catheters are frequently used. The commonest cause of catheter-related bloodstream infections (CRBSI) is coagulase-negative staphylococci (CoNS) associated with adherent biofilm. Tigecycline, a derivative of tetracycline, acts against strains producing biofilm. In this study, we aimed to determine the effect of tigecycline in a CRBSI model. A single dose of 10(8) colony-forming units (CFU)/mL of slime-producing Staphylococcus epidermidis was given through polyethylene catheters inserted into 24 rabbits. After 72 h, groups of eight rabbits were treated with heparin, vancomycin/heparin or tigecycline/heparin. Blood obtained from peripheral veins and the catheter lumen as well as catheter tips were cultured, and three catheters from each group were studied using electron microscopy. Surfaces were randomly subdivided and areas with ≥50 bacteria were compared. Blood cultures were positive from all heparin-treated rabbits but were negative from those receiving either antibiotic (P<0.001). Catheter tip cultures revealed growth from six, two and one rabbit(s) given heparin, vancomycin and tigecycline, respectively. Electron microscopy showed that catheters from heparin-treated rabbits were most heavily colonised (more areas with ≥50 CFU) compared with catheters from animals treated with vancomycin or tigecycline (P<0.003 and P<0.001, respectively). In conclusion, this study shows that tigecycline and vancomycin are both effective for treating CRBSI due to CoNS. Electron microscopy of catheters themselves suggests that tigecycline is superior to vancomycin (P<0.001). Tigecycline may be useful for the treatment of CRBSI.     

药师参与替加环素治疗耐多药鲍曼不动杆菌肺部感染2例的体会

目的：通过2个具体案例,总结替加环素临床应用中存在的一些问题,为临床药师进行药学监护提供参考。方法：对2例不规范使用替加环素治疗耐多药鲍曼不动杆菌的病例进行总结、分析及监护。结果与结论：对于耐多药鲍曼不动杆菌可以选择替加环素治疗,但是需要考虑剂量和疗程问题。同时,临床药师应将所学应用于临床实践中,以促进临床合理用药。     

What role for tigecycline in infections?

Tigecycline (pronounced tie-ge-sigh-cleen; Tygacil--Wyeth) is a broad-spectrum antibacterial and the first glycylcycline to be marketed in the UK. It is active against certain resistant bacteria, including meticillin-resistant Staphylococcus aureus (MRSA) and bacteria that produce extended-spectrum beta-lactamase (ESBL). Tigecycline is licensed for intravenous treatment of adults with complicated skin and soft tissue infections, and complicated intra-abdominal infections. We review tigecycline and assess its place for these infections.     

The glycylcyclines: a comparative review with the tetracyclines

The tetracycline class of antimicrobials exhibit a broad-spectrum of activity against numerous pathogens, including Gram-positive and Gram-negative bacteria, as well as atypical organisms. These compounds are bacteriostatic, and act by binding to the bacterial 30S ribosomal subunit and inhibiting protein synthesis. The tetracyclines have been used successfully for the treatment of a variety of infectious diseases including community-acquired respiratory tract infections and sexually transmitted diseases, as well in the management of acne. The use of tetracyclines for treating bacterial infections has been limited in recent years because of the emergence of resistant organisms with efflux and ribosomal protection mechanisms of resistance. Research to find tetracycline analogues that circumvented these resistance mechanisms has lead to the development of the glycylcyclines. The most developed glycylcycline is the 9-tert-butyl-glycylamido derivative of minocycline, otherwise known as tigecycline (GAR-936). The glycylcyclines exhibit antibacterial activities typical of earlier tetracyclines, but with more potent activity against tetracycline-resistant organisms with efflux and ribosomal protection mechanisms of resistance. The glycylcyclines are active against other resistant pathogens including methicillin-resistant staphylococci, penicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant enterococci. Tigecycline is only available in an injectable formulation for clinical use unlike currently marketed tetracyclines that are available in oral dosage forms. Tigecycline has a significantly larger volume of distribution (> 10 L/kg) than the other tetracyclines (range of 0.14 to 1.6 L/kg). Protein binding is approximately 68%. Presently no human data are available describing the tissue penetration of tigecycline, although studies in rats using radiolabelled tigecycline demonstrated good penetration into tissues. Tigecycline has a half-life of 36 hours in humans, less than 15% of tigecycline is excreted unchanged in the urine. On the basis of available data, it does not appear that the pharmacokinetics of tigecycline are markedly influenced by patient gender or age. The pharmacodynamic parameter that best correlates with bacteriological eradication is time above minimum inhibitory concentration. Several animal studies have been published describing the efficacy of tigecycline. Human phase 1 and 2 clinical trials have been completed for tigecycline. Phase 2 studies have been conducted in patients with complicated skin and skin structure infections, and in patients with complicated intra-abdominal infections have been published as abstracts. Both studies concluded that tigecycline was efficacious and well tolerated. Few human data are available regarding the adverse effects or drug interactions resulting from tigecycline therapy; however, preliminary data report that tigecycline can be safely used, is well tolerated and that the adverse effects experienced were typical of the tetracyclines (i.e. nausea, vomiting and headache). Tigecycline appears to be a promising new antibacterial based on in vitro and pharmacokinetic/pharmacodynamic activity; however more clinical data are needed to fully evaluate its potential.