文献报道的替加环素诱发肾移植患者急性胰腺炎11例分析

摘要：目的:探究文献报道的替加环素致肾移植术后患者急性胰腺炎的特点,为肾移植术后患者使用替加环素的安全提供参考。方法:检索国内外数据库中收录的替加环素诱发肾移植术后患者急性胰腺炎的个案报道,对纳入文献中患者基本信息及出现不良反应(ADR)情况进行统计分析。结果:共纳入11个病例,其中男8例,女3例,平均年龄(42.82±11.36)岁;10例患者合并使用免疫抑制药;9例(81.82%)患者的ADR诱导期在10d以内,8例(72.73%)患者初期临床表现主要是腹痛,6例(54.54%)为恶心、呕吐、腹胀;除1例未报道外,其他患者的血清淀粉酶和脂肪酶均高于正常值。所有患者均停药、对症处理,(3.56±1.26)d后临床症状逐渐改善,(6.3±5.06)d后血清淀粉酶和脂肪酶水平恢复正常。结论:肾移植术后患者使用替加环素应慎重,一旦发生急性胰腺炎需立即停药并对症处理。     

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。     

替加环素适合于治疗复杂感染

替加环素(Tigecycline)是9-叔丁基甘氨酰胺米诺环素衍生物，对由携带有四环素耐药决定子的病原菌引起的急性致死性感染有效。与米诺环素比较，替加环素服用次数更少或剂量更低。替加环素对革兰阳性和阴性菌具有良好的抗菌活性，包括引起腹腔内、皮肤组织和下呼吸道感染的耐药革兰阴性菌，特别是引起下呼吸道感染的其他非典型病原菌。     

替加环素致重症感染患者发生低纤维蛋白原血症的危险因素分析

目的 分析替加环素致重症感染患者发生低纤维蛋白原血症的相关危险因素。方法 101例重症医学科接受替加环素治疗的重症感染患者,根据应用替加环素后患者是否发生低纤维蛋白原血症分为低FIB组[发生低纤维蛋白原血症,纤维蛋白原(FIB)<2.0 g/L, 43例]和对照组(未发生低纤维蛋白原血症, FIB≥2.0 g/L, 58例)。统计患者的临床资料,分析替加环素致低纤维蛋白原血症的危险因素,停用替加环素后FIB水平变化情况。结果 单因素分析结果发现,低FIB组的腹腔感染占比41.86%、维持剂量100 mg q.12 h.占比30.23%高于对照组的10.34%、12.07%,用替加环素前FIB水平(3.71±1.27)g/L低于对照组的(4.65±1.49)g/L,替加环素应用时间(8.98±2.47)d长于对照组的(7.33±2.33)d(P<0.05)。两组年龄、性别、基础疾病、既往手术史、应用替加环素前序贯器官衰竭评分(SOFA)评分、应用替加环素前急性生理学和慢性健康评估系统Ⅱ(APACHEⅡ)评分、致病菌、用替加环素前器官功能、负荷剂量100 mg、联合应用头孢哌酮...     

替加环素对重症急性胰腺炎患者肝功能、淀粉酶及凝血功能的影响

目的:分析替加环素对重症急性胰腺炎患者肝功能、淀粉酶及凝血功能的影响,为合理使用替加环素提供参考.方法:回顾性选择某院2017年6月至2019年5月期间使用替加环素治疗的重症急性胰腺炎患者,共纳入51例.根据用药前总胆红素(TBIL)、直接胆红素(DBIL)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱...     

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。     

二肽基肽酶Ⅳ抑制剂与急性胰腺炎

二肽基肽酶IV（DPP-4）抑制剂是新型口服降糖药物,该类药物能有效降低糖化血红蛋白,耐受性与安全性较好,急性胰腺炎是其少见而严重的不良反应。DPP-4抑制剂致急性胰腺炎潜伏期为14～515d,临床表现为上腹部疼痛,实验室检查可见血清淀粉酶、脂肪酶和弹性蛋白酶水平显著升高。病理学检查可见胰腺和胰周组织水肿和坏死。DPP-4抑制剂致急性胰腺炎的机制主要涉及变态反应和药物或代谢产物对胰腺的直接毒性。有胰腺炎病史者应慎用DPP-4抑制剂。密切注意患者用药情况并监测血清淀粉酶、脂肪酶和弹性蛋白酶水平,是预防DPP-4抑制剂致急性胰腺炎发生和发展的有效措施。     

血清淀粉酶和脂肪酶联合检测对急性胰腺炎的诊断价值

目的探讨血清淀粉酶和脂肪酶联合检测对急性胰腺炎的诊断价值。方法对33例型胰腺炎患者、7例重型胰腺炎患者及40例健康体检者进行血清淀粉酶和脂肪酶检测。结果胰腺炎患者的血清淀粉酶和脂肪酶水平明显高于健康人(P <0.05),重型胰腺炎明显高于轻型胰腺炎(P <0.05)。血清脂肪酶诊断急性胰腺炎的灵敏度、特异度、准确度分别为62.3%、60.2%、61.9%;淀粉酶分别为63.5%、64.4%、65.1%,联合检测分别为85.3%、85.3%、85.3%。结论在急性胰腺炎的检测中,联合血清脂肪酶、淀粉酶可以提高诊断的准确性,为临床提供更为科学的依据。     

替加环素致不良反应的国内外文献分析

目的：探讨替加环素致药品不良反应(ADR)发生的特点及规律,为临床合理用药提供参考。方法：检索中国知网、维普数据库、万方数据库、PubMed、Web of Sciene和Embase等数据库中2005年1月至2022年8月发表的替加环素致ADR的个案报道,进行统计分析。结果：共纳入替加环素致ADR相关文献91篇,提取病例108例,其中男性68例,女性37例,性别不详3例;患者年龄主要为≥60岁(61例,占56.48%);患者原患疾病主要为肺部感染及腹腔感染。替加环素致ADR的发生时间为给药后10 min至给药后2.5个月,大多数ADR发生于给药后7 d内(72例,占66.67%)。替加环素所致ADR累及多个器官和(或)系统,共219例次,其中消化系统损害(105例次,占47.95%)最为常见,其次为血液系统损害(77例次,占35.16%)。大多数发生ADR的患者经停药或积极对症治疗后,1周内症状均有好转(68例,占62.96%)。结论：替加环素所致ADR可累及多个器官和(或)系统,临床表现多样,用药期间应加强替加环素致ADR的认识与监测,以减少或避免ADR的发生,保障患者安全用药。     

不动杆菌对替加环素及多黏菌素耐药机制研究进展

不动杆菌属细菌是临床常见的非发酵糖菌,广泛分布于医院环境中,是引起多种院内感染的重要条件致病菌.随着临床抗菌药物的大量使用,不动杆菌逐渐出现了多重耐药甚至全耐药株,有效抗菌药物极少,给临床感染的治疗带来极大困难.近年来发现替加环素和多黏菌素治疗多重耐药革兰阴性菌感染特别是鲍曼不动杆菌有较好疗效,但随着研究的不断深入,逐渐发现不动杆菌对替加环素及多黏菌素也存在耐药性,本文就目前国内外不动杆菌对替加环素及多黏菌素耐药机制进行简要综述.不动杆菌对替加环素耐药机制主要与AdeABC外排泵系统有关,对多黏菌素的耐药机制主要为外膜LPS修饰.还需要针对不动杆菌对替加环素及多黏菌素的耐药机制进一步研究,从而指导临床合理使用抗菌药物.     

Tigecycline-induced acute pancreatitis: case report and literature review

Tigecycline is a broad-spectrum antimicrobial agent structurally related to minocycline. Pancreatitis has been associated with the tetracycline class of antibiotics and concerns about tigecycline-induced acute pancreatitis have recently been raised. We describe a 69-year-old female who received tigecycline for treatment of a complicated skin and skin-structure infection. Following 7 days of tigecycline she developed severe abdominal pain and elevated pancreatic enzymes suggesting acute pancreatitis. According to the Naranjo adverse drug reaction probability scale, tigecycline was the probable cause of her acute pancreatitis. Clinicians should be aware of this potential adverse effect of tigecycline. We recommend that clinicians monitor patients for signs and symptoms of pancreatitis, including abdominal pain, during treatment with tigecycline.     

过敏性紫癜合并急性胰腺炎23例临床分析

目的总结过敏性紫癜(过敏性紫癜)合并急性胰腺炎(急性胰腺炎)的临床特征,提高临床认识,减少误诊,改善预后。方法回顾性分析23例诊断为过敏性紫癜合并急性胰腺炎患儿的临床资料。分析临床特征,实验室检查结果,影像学表现,治疗和总体预后。结果所有患儿均有腹部表现,包括明显腹痛20例,呕吐18例,腹胀12例,13例柏油样粪便。虽然所有患儿都有典型的皮肤紫癜,但8例患儿在临床上表现为急性腹痛为首发症状。所有患儿血液中血清淀粉酶,血清脂肪酶,尿淀粉酶水平增高。并且腹部超声检查发现14例胰腺肿胀。胃镜检查阳性率100%。糖皮质激素治疗可有效缓解腹痛症状。所有患儿均预后良好。出院后6~12个月未出现任何腹部并发症。结论在过敏性紫癜儿童中急性胰腺炎发病率低,与过敏性紫癜的腹部表现在临床上无特异性。因此,在过敏性紫癜患儿有严重的腹痛时,应评估血清淀粉酶水平确诊急性胰腺炎。早期诊断过敏性紫癜伴急性胰腺炎,并及时治疗有助于改善预后。     

新一代抗菌药物替加环素的研究进展

替加环素是一种新型四环素类静脉注射用抗菌药物,它具有广谱、高效等特点．对多种病原体有效,如耐甲氧西林金黄色葡萄球菌．耐万古霉素肠球菌．多药耐药肺炎链球菌,广谱β-内酰胺酶革兰阴性菌和鲍曼不动杆菌抗菌等。目前批准的适应证包括复杂性皮肤和复杂腹内感染．同时也可有效治疗社区获得性及医院感染性肺炎。本文对替加环素的药理作用、药动学、临床研究、药物相互作用、不良反应等方面等进行综述。     

新型静脉用甘氨酰环素类抗菌药替加环素

替加环素是第一个用于临床的可供静脉注射的广谱甘氨酰环素抗菌药，它克服了由细菌外排及核糖体保护所导致的四环素耐药性。在体外试验中，对大多数G^＋和G^-需氧菌及厌氧菌有效，可用于治疗成人复杂皮肤及其软组织感染（cSSSIs）和成人复杂的腹内感染（cIAIs），且耐受性良好。     

Metabolism, excretion, and pharmacokinetics of [14C]tigecycline, a first-in-class glycylcycline antibiotic, after intravenous infusion to healthy male subjects.

Tigecycline, a novel, first-in-class glycylcycline antibiotic, has been approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections. The pharmacokinetics, metabolism, and excretion of [(14)C]tigecycline were examined in healthy male volunteers. Tigecycline has been shown to bind to bone; thus, to minimize the amount of radioactivity binding to bone and to maximize the recovery of radioactivity, tigecycline was administered intravenously (30-min infusion) as a single 100-mg dose, followed by six 50-mg doses, every 12 h, with the last dose being [(14)C]tigecycline (50 microCi). After the final dose, the pharmacokinetics of tigecycline in serum showed a long half-life (55.8 h) and a large volume of distribution (21.0 l/kg), whereas radioactivity in serum had a shorter half-life (6.9 h) and a smaller volume of distribution (3.3 l/kg). The major route of elimination was feces, containing 59% of the radioactive dose, whereas urine contained 32%. Unchanged tigecycline was the predominant drug-related compound in serum, urine, and feces. The major metabolic pathways identified were glucuronidation of tigecycline and amide hydrolysis followed by N-acetylation to form N-acetyl-9-aminominocycline. The glucuronide metabolites accounted for 5 to 20% of serum radioactivity, and approximately 9% of the dose was excreted as glucuronide conjugates within 48 h. Concentrations of N-acetyl-9-aminominocycline were approximately 6.5% and 11% of the tigecycline concentrations in serum and urine, respectively. Excretion of unchanged tigecycline into feces was the primary route of elimination, and the secondary elimination pathways were renal excretion of unchanged drug and metabolism to glucuronide conjugates and N-acetyl-9-aminominocycline.     

The prevalence of pancreatitis in organophosphate poisonings

OBJECTIVE: The aim of this study was to evaluate the prevalence of pancreatitis in cases of organophosphate (OP) poisonings admitted to Yüzüncü Yil University Teaching Hospital over an 18-month period. MATERIALS AND METHODS: A total of 47 patients of acute poisoning with OP insecticides attended the Emergency Department of the Yüzüncü Yil Medical School Hospital, from May 1999 to December 2000, and were prospectively studied. Serum amylase and lipase levels were studied with colorimetric assay. Serum SGOT, SGPT, LDH, CPK, K levels, leukocyte count and total hospitalization days were also evaluated. RESULTS: Four of 47 patients had obviously elevated amylase and lipase levels (amylase >300 U/L, lipase >60 U/L). Only two of the patients with amylase levels between 100 and 300 U/L had also elevated levels of lipase. None of the patients with normal amylase levels had elevated levels of lipase. A total of 12.76% was diagnosed as acute pancreatitis. CONCLUSION: Acute pancreatitis as a complication of OP intoxication is not a rare condition. In order to improve the outcome of OP poisoning, early diagnosis of acute pancreatitis is important and serum levels of amylase and lipase should be routinely considered carefully. In acute pancreatitis, serum levels of SGOT, SGPT, LDH and leukocyte counts may also be found to be elevated. However, serum K levels are only slightly decreased.     

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.     

替加环素相关凝血功能障碍文献概述

摘 要替加环素(tigecycline)是一种新型广谱抗生素,为首个应用于临床的甘氨酰环素类抗生素,对革兰阳性球菌、革兰阴性杆菌和厌氧菌,特别是多药耐药(multidrug resistant,MDR)致病菌有很强的抗菌活性。本文检索PubMed收录的相关文献,综述替加环素相关凝血功能障碍的临床特点和研究现状,探讨发生机制。建议用药期间临床医师应密切监测各项凝血指标,发生凝血功能障碍和活动性出血时应立即停药并给予积极的对症支持治疗。     

Tigecycline: first of a new class of antimicrobial agents

Tigecycline is the first commercially available member of the glycylcyclines, a new class of antimicrobial agents. The glycylcyclines are derivatives of the tetracycline antibiotics, with structural modifications that allow for potent gram-positive, gram-negative, and anaerobic activity, including certain multidrug-resistant strains. The enhanced activity can be attributed to stronger binding affinity and enhanced protection against several mechanisms of resistance that affect other antibiotic classes such as tetracyclines. Tigecycline exhibits generally bacteriostatic action by reversibly binding to the 30S ribosomal subunit and inhibiting protein translation. In vitro activity has been demonstrated against multidrug-resistant gram-positive pathogens including methicillin-resistant and glycopeptide-intermediate and -resistant Staphylococcus aureus, as well as vancomycin-resistant enterococci. Multidrug-resistant gram-negative pathogens, such as Acinetobacter baumannii and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli, are typically highly susceptible to tigecycline. The drug also has displayed significant activity against many clinically important anaerobic organisms. This agent demonstrates a predictable pharmacokinetic profile and minimal drug interactions, and is generally well tolerated, with nausea being the most common adverse event. It was approved in June 2005 for the treatment of complicated skin and skin structure infections (SSSIs) and complicated intraabdominal infections. Currently, a limited number of broad-spectrum antimicrobials are available to combat multidrug-resistant organisms. The addition of new agents is essential to limiting the spread of these pathogens and improving outcomes in patients with these types of infections. Tigecycline has demonstrated promising results in initial in vitro and clinical studies for SSSIs and complicated intraabdominal infections; however, further clinical experience will clarify its role as a broad-spectrum agent.