Tetracyclines

四环素
  • DOI:
    文章类型: Journal Article
    围手术期皮炎(POD)是一种常见的,慢性,炎性面部皮肤皮疹,表现为微小丘疹和丘疹脓疱,带有潜在的湿疹样斑块,通常局限于口周,经鼻,和眶周区域。目前尚无食品和药物管理局(FDA)指定的POD治疗方法;但是,广谱抗生素作为一种有效的治疗选择。广谱抗生素对肠道菌群产生负面影响并导致抗生素耐药性。窄谱四环素,比如sarreccine,具有促进细菌耐药性和胃肠道问题的低潜力。
    我们进行了回顾性图表回顾,以评估在一组被诊断为POD的患者中使用sarecycine的疗效。
    使用电子病历完成病历审查。纳入标准包括18至95岁的男性和女性,诊断为POD,用sareccine治疗,并进行了有记录的随访。
    6名患者符合纳入标准,所有这些都显示出改善,没有报道的副作用。六个病人中,4例为女性,2例为男性,患者年龄为26~58岁(平均41岁).疗程为30至180天(中位数=90天)。
    根据结果,与替代的四环素类抗生素相比,使用sareccine治疗POD有许多潜在的益处.需要更大规模的临床研究来评估POD的治疗选择。基于在大规模痤疮研究中的功效和耐受性,sarecycline可能是POD的一种合适的新型治疗选择,应进一步探索。
    UNASSIGNED: Periorificial dermatitis (POD) is a common, chronic, inflammatory facial skin rash that presents as tiny papules and papulopustules with underlying eczematous-like patches, typically confined to the perioral, perinasal, and periorbital areas. There is currently no Food and Drug Administration (FDA)-indicated treatment for POD; however, broad-spectrum antibiotics are efficacious as a treatment option. Broad-spectrum antibiotics negatively impact gut flora and lead to antibiotic resistance. Narrow-spectrum tetracyclines, such as sarecycline, have a low potential for promoting bacterial resistance and gastrointestinal issues.
    UNASSIGNED: We conducted a retrospective chart review in order to evaluate the efficacy of sarecycline in a cohort of patients diagnosed with POD that were treated with sarecycline.
    UNASSIGNED: A review of medical records was completed using an electronic medical record. Inclusion criteria included males and females aged 18 to 95 with a diagnosis of POD, treated with sarecycline with a documented follow-up.
    UNASSIGNED: Six patients met inclusion criteria, all of which had shown improvement with no reported side effects. Of the six patients, four were female and two were male and the patient ages ranged from 26 to 58 years old (mean=41 years). The course of therapy ranged from 30 to180 days (median=90 days).
    UNASSIGNED: Based on the outcomes, there are many potential benefits to treatment of POD with sarecycline over the alternative tetracycline-class antibiotics. There is a need for more large-scale clinical studies evaluating treatment options for POD. Based on the efficacy and tolerability of sarecycline in large- scale acne studies, sarecycline may be an appropriate novel treatment option for POD and should be explored further.
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  • 文章类型: Journal Article
    该研究旨在获得8岁以下儿童四环素类药物的真实世界安全性概况,并为临床药物应用提供参考。
    我们通过OpenVigil2对FDA不良事件报告系统(FAERS)数据库进行了不成比例的分析,并对8岁以下儿童四环素类药物不良反应(ADR)的病例报告进行了审查。
    FAERS分析确定了8岁以下儿童的32种四环素类药物不良反应。呼吸,在所有系统器官类别(SOC)中,胸部和纵隔疾病的ADR最为常见.比例报告比(PRR)最高的前3位阳性信号为喉部损伤,霍纳综合征和高铁血红蛋白血症。文献中发现了16例8岁以下儿童四环素相关病例,集中在三个SOC中。胃肠道疾病是最常见的病例(n=12)。
    在我们的研究中,仅在8岁以下的儿童中新报告了几种不良反应,包括霍纳综合征和高铁血红蛋白血症。我们建议临床从业人员应在说明书和标签之外注意ADR。密切照顾孩子,并在治疗不可避免时及时进行干预。
    UNASSIGNED: The study aims to obtain the real-world safety profile of tetracyclines in children younger than 8 years old and provide reference for clinical drug applications.
    UNASSIGNED: We made a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database through OpenVigil 2 and conducted a review of case reports regarding adverse drug reactions (ADRs) of tetracyclines in children younger than 8-year-old.
    UNASSIGNED: FAERS analysis identified 32 ADRs of tetracyclines in children younger than 8-year-old. Respiratory, thoracic, and mediastinal disorders contained the most frequent ADRs among all system organ classes (SOCs). The top three positive signals with the highest proportional reporting ratio (PRR) were laryngeal injury, Horner\'s syndrome and methaemoglobinaemia. Sixteen published tetracyclines-associated cases in children younger than 8-year-old were identified in the literature, concentrating in three SOCs. Gastrointestinal disorders were the most commonly reported cases (n = 12).
    UNASSIGNED: Several ADRs were newly reported only in children younger than 8-year-old in our research, including Horner\'s syndrome and methemoglobinemia. We recommended that the clinical practitioners should pay attention to the ADRs both in instruction and beyond the label. Take close care of children and timely intervene when the treatment is inevitable.
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  • 文章类型: Journal Article
    多重耐药生物的威胁不断升级,需要不断探索新型抗菌剂。埃拉瓦环素,下一代四环素衍生物,由于其独特的化学结构,已经成为一种有前途的解决方案,增强效力并扩展其活性范围。
    这篇综述提供了对埃拉环素的全面检查,包括其对革兰氏阳性和革兰氏阴性需氧菌的体外活性,碳青霉烯-非易感生物,厌氧菌,和其他细菌菌株。此外,它评估来自临床研究的证据,以确定其临床效果和安全性。
    埃拉瓦环素,一种合成的氟环环素,属于四环素类,具有基本的化学结构,并在石脑环的D环上引入了特定的修饰。类似于其他四环素,埃拉环素通过可逆结合细菌核糖体30S亚基发挥其抗菌作用,防止氨基酸残基掺入延伸的肽链并最终破坏细菌蛋白质合成。埃拉伐环素对许多革兰氏阳性和革兰氏阴性需氧菌显示出有效的体外活性,厌氧菌,和多重耐药生物。随机对照试验及其相关荟萃分析证实了埃拉环素治疗复杂腹腔感染的疗效。此外,真实世界的研究展示了埃拉环素在不同临床条件下的适应性和有效性,强调其超越标签适应症的效用。尽管常见的胃肠道不良事件,eravacycline保持整体良好的安全性,加强其作为可耐受抗生素的地位。然而,正在进行的研究对于精炼埃拉环素的作用至关重要,探索联合治疗,并评估其对生物膜的性能,有助于其在对抗具有挑战性的细菌感染方面的持续成功。
    UNASSIGNED: The escalating threat of multidrug-resistant organisms necessitates constant exploration for novel antimicrobial agents. Eravacycline has emerged as a promising solution due to its unique chemical structure, which enhances potency and expands its spectrum of activity.
    UNASSIGNED: This review provides a thorough examination of eravacycline, encompassing its in vitro activity against Gram-positive and Gram-negative aerobes, carbapenem-non-susceptible organisms, anaerobes, and other bacterial strains. Additionally, it evaluates evidence from clinical studies to establish its clinical effect and safety.
    UNASSIGNED: Eravacycline, a synthetic fluorocycline, belongs to the tetracyclines class. Similar to other tetracycline, eravacycline exerts its antibacterial action by reversibly binding to the bacterial ribosomal 30S subunit. Eravacycline demonstrates potent in vitro activity against many Gram-positive and Gram-negative aerobes, anaerobes, and multidrug-resistant organisms. Randomized controlled trials and its associated meta-analysis affirm eravacycline\'s efficacy in treating complicated intra-abdominal infections. Moreover, real-world studies showcase eravacycline\'s adaptability and effectiveness in diverse clinical conditions, emphasizing its utility beyond labeled indications. Despite common gastrointestinal adverse events, eravacycline maintains an overall favorable safety profile, reinforcing its status as a tolerable antibiotic. However, ongoing research is essential for refining eravacycline\'s role, exploring combination therapy, and assessing its performance against biofilms, in combating challenging bacterial infections.
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  • 文章类型: Journal Article
    肺炎支原体对大环内酯类药物的耐药性不断升级已成为全球健康关注的重要问题。特别是在低收入和中等收入国家(LMICs)。虽然四环素和喹诺酮类药物已被提议作为替代治疗选择,对特定年龄的安全问题的担忧以及在各种国家指南的建议中缺乏共识。因此,本研究的主要目的是确定对肺炎支原体感染二线治疗最有效的干预措施,同时考虑与这些干预措施相关的年龄特异性安全性问题.
    在这篇系统综述和网络荟萃分析中,我们搜索了PubMed,Embase,CNKI,和万方数据,从成立到11月11日,2023年。收集喹诺酮类药物或四环素类药物治疗肺炎支原体感染的研究,并通过阅读已发表的报告进行筛选,包括任何类型的研究,并且不需要个人患者级别的数据。系统评价和直接荟萃分析比较了四环素和喹诺酮类药物在退热时间(TTD)方面的疗效以及抗生素给药24小时和48小时内的发热消失率。用于管理肺炎支原体感染。贝叶斯网络荟萃分析(NMA)用于间接评估不同干预措施对肺炎支原体感染患者的相对有效性以及儿科患者的药物安全性。这项研究在PROSPERO注册,CRD42023478383。
    系统回顾和直接荟萃分析共纳入4篇文章,涉及246例患者,而NMA包含85篇文章,涉及7095名患者的大量队列。NMA测量了所有年龄段的有效性,包括7043名患者,平均年龄为37.80±3.91岁。在纳入的85项研究中,14人(16.5%)存在低偏倚风险,71人(83.5%)处于中等风险,并且没有一项研究被认为存在高偏倚风险.在直接荟萃分析中,关于TTD,四环素和喹诺酮类药物之间无统计学差异(平均差:-0.40,95%CI:-1.43至0.63;I2=0%),抗生素给药24小时内的发热消失率(OR:0.37,95%CI:0.08-1.79;I2=58%),抗生素给药48h内的发热消失率(OR:1.10,95%CI:0.30-3.98;I2=59%)。然而,临床反应的综合NMA分析(在70项研究中;n=6143例患者),TTD缩短(52项研究;n=4363例),咳嗽缓解或消失的时间缩短(在39项研究中;n=3235例患者),在48小时的发热消失率(在四项研究中,n=418例患者)显示,米诺环素在这些不同的参数中表现出最有利的结果,和24小时发热消失率的分析(在三项研究中,n=145名患者)显示,左氧氟沙星可能是最有效的,如累积排名面积(SUCRA)值下的排名概率和表面所示。莫西沙星在临床反应和缩短咳嗽缓解或消失时间方面排名第二,第三是缩短TTD。值得注意的是,在评估儿科患者不良反应的发生时(在四项研究中;n=239名儿童),左氧氟沙星与不良事件发生率最高的SUCRA值排名相关.
    我们的研究结果表明,四环素和喹诺酮类药物可能同样有效。根据纳入研究的参与者的年龄,在考虑所有预防措施的情况下,米诺环素可能是八岁以上儿童最有效的干预措施,而莫西沙星可能使8岁以下的人受益。然而,这些结果应谨慎解释,鉴于研究和患者数量有限,以及纳入研究之间的异质性。根据对儿童的有限研究,左氧氟沙星可能是不良反应发生率最高的药物之一。NMA中的大多数研究都来自亚洲地区,更多的随机对照试验比较肺炎支原体患者的不同治疗策略是必要的。这项比较研究为临床药剂师和临床医生提供了重要信息,使他们能够就治疗方案做出明智的决定。考虑药物疗效和安全性。
    福建省自然科学基金,中国。
    UNASSIGNED: The escalating resistance of Mycoplasma pneumoniae to macrolides has become a significant global health concern, particularly in low-income and middle-income countries (LMICs). Although tetracyclines and quinolones have been proposed as alternative therapeutic options, concerns regarding age-specific safety issues and the lack of consensus in recommendations across various national guidelines prevail. Thus, the primary objective of this study is to ascertain the most efficacious interventions for second-line treatment of M. pneumoniae infection while considering the age-specific safety issues associated with these interventions.
    UNASSIGNED: In this systematic review and network meta-analysis we searched PubMed, Embase, CNKI, and WanFang Data, from inception up to November 11th, 2023. Studies of quinolones or tetracyclines for the treatment of people with M. pneumoniae infection were collected and screened by reading published reports, with any type of study included, and no individual patient-level data requested. A systematic review and direct meta-analysis compared the efficacy of tetracyclines and quinolones regarding time to defervescence (TTD) and the rates of fever disappearance within 24 h and 48 h of antibiotic administration, for managing M. pneumoniae infection. Bayesian network meta-analysis (NMA) was employed to indirectly assess the relative effectiveness of different interventions in people with M. pneumoniae infection and the safety profile of medication in paediatric patients. This study is registered with PROSPERO, CRD42023478383.
    UNASSIGNED: The systematic review and direct meta-analysis included a total of 4 articles involving 246 patients, while the NMA encompassed 85 articles involving a substantial cohort of 7095 patients. The NMA measured the effectiveness across all ages and included 7043 patients, with a mean age of 37.80 ± 3.91 years. Of the 85 included studies, 14 (16.5%) were at low risk of bias, 71 (83.5%) were at moderate risk, and no studies were rated as having a high risk of bias. In the direct meta-analysis, no statistically significant differences were found between tetracyclines and quinolones concerning TTD (mean difference: -0.40, 95% CI: -1.43 to 0.63; I2 = 0%), fever disappearance rate within 24 h of antibiotic administration (OR: 0.37, 95% CI: 0.08-1.79; I2 = 58%), and fever disappearance rate within 48 h of antibiotic administration (OR: 1.10, 95% CI: 0.30-3.98; I2 = 59%). However, the comprehensive NMA analysis of clinical response (in 70 studies; n = 6143 patients), shortening of TTD (in 52 studies; n = 4363 patients), shortening length of cough relief or disappearance (in 39 studies; n = 3235 patients), fever disappearance rate at 48 h (in four studies; n = 418 patients) revealed that minocycline exhibited the most favourable outcomes across these various parameters, and the analysis of fever disappearance rate at 24 h (in three studies; n = 145 patients) revealed that levofloxacin may be the most effective, as indicated by the rank probabilities and surface under the cumulative ranking area (SUCRA) value. Moxifloxacin ranked second in clinical response and in shortening the length of cough relief or disappearance, and third in shortening TTD. Notably, when evaluating the occurrence of adverse reactions in paediatric patients (in four studies; n = 239 children), levofloxacin was associated with the highest SUCRA value rankings for the rate of adverse events.
    UNASSIGNED: Our findings suggest that tetracyclines and quinolones may be equally effective. Based on the age of participants in the included studies, minocycline may be the most effective intervention for children over eight years of age when all preventive measures are considered, whereas moxifloxacin may benefit people under eight years of age. However, these results should be interpreted with caution, given the limited number of studies and patients included, and the heterogeneity between included studies. Based on a limited number of studies in children, levofloxacin is likely to have one of the highest rates of adverse reactions. The majority of the studies included in the NMA were from the Asian region, and more randomised controlled trials comparing different therapeutic strategies in patients with M. pneumoniae are warranted. This comparative study provides clinical pharmacists and clinicians with important information to enable them to make informed decisions about treatment options, considering drug efficacy and safety.
    UNASSIGNED: The Natural Science Foundation of Fujian Province, China.
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  • 文章类型: Meta-Analysis
    对于使用多西环素暴露后预防(PEP)来降低细菌性性传播感染(STIs)的发生率存在相当大的兴趣。一个重要的问题是,这可能会在这些性传播感染和其他物种中选择四环素抗性。我们搜索了PubMed和谷歌学者,(1948-2023)用于比较四环素PEP与非四环素对照的随机对照试验。主要结果是所有细菌物种对四环素的抗菌素耐药性(AMR),有可用数据。我们的搜索产生了140项研究,其中三人符合纳入标准。四环素PEP与淋病奈瑟菌对四环素耐药的患病率增加有关,但这一效应无统计学意义(汇集OR2.3,95%CI0.9-3.4).在一项研究中,PEP对淋病奈瑟菌四环素MIC分布具有显著影响,其中对此进行了评估。预防性功效在低MIC时为100%,在高MIC时为0%。在一项评估的研究中,与对照组相比,PEP导致共生奈瑟菌对四环素的耐药性显着增加(OR2.9,95%CI1.5-5.5),但对金黄色葡萄球菌对四环素的耐药性没有显着影响。现有证据表明,四环素的PEP可能与淋病奈瑟菌和共生奈瑟菌的四环素抗性选择有关。
    There is considerable interest in the use of doxycycline post exposure prophylaxis (PEP) to reduce the incidence of bacterial sexually transmitted infections (STIs). An important concern is that this could select for tetracycline resistance in these STIs and other species. We searched PubMed and Google Scholar, (1948-2023) for randomized controlled trials comparing tetracycline PEP with non-tetracycline controls. The primary outcome was antimicrobial resistance (AMR) to tetracyclines in all bacterial species with available data. Our search yielded 140 studies, of which three met the inclusion criteria. Tetracycline PEP was associated with an increasedprevalence of tetracycline resistance in Neisseria gonorrhoeae, but this effect was not statistically significant (Pooled OR 2.3, 95% CI 0.9-3.4). PEP had a marked effect on the N. gonorrhoeae tetracycline MIC distribution in the one study where this was assessed. Prophylactic efficacy was 100% at low MICs and 0% at high MICs. In the one study where this was assessed, PEP resulted in a significant increase in tetracycline resistance in commensal Neisseria species compared to the control group (OR 2.9, 95% CI 1.5-5.5) but no significant effect on the prevalence of tetracycline resistance in Staphylococcus aureus. The available evidence suggests that PEP with tetracyclines could be associated with selecting tetracycline resistance in N. gonorrhoeae and commensal Neisseria species.
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  • 文章类型: Journal Article
    四环素是最常用的抗生素之一,用于治疗细菌感染以及改善农业生长和饲料效率。四环素组中的所有化合物(四环素,金霉素,多西环素,和土霉素)在尿液中以未改变的形式排泄,排泄率超过70%。它们以改变和未改变的形式进入水生环境,影响水生微生物和大型生物。本研究回顾了发生的情况,命运,以及欧洲四环素污染的去除技术。水中四环素污染的平均水平为0至20ng/L。然而,有关四环素类药物污染环境的数据仍然不足。尽管四环素在环境中不断存在和影响,四环素类物质排放到水生环境中没有法律限制。为了应对这些挑战,各种去除技术,包括高级氧化,吸附,和紫外线处理,正在进行批判性评估和比较。总结的数据有助于更好地了解欧洲水域的现状,并提供对未来环境管理和政策制定的潜在战略的见解。因此,需要进一步研究四环素在水生环境中的污染和影响。
    Tetracyclines are among the most commonly used antibiotics for the treatment of bacterial infections and the improvement of agricultural growth and feed efficiency. All compounds in the group of tetracyclines (tetracycline, chlorotetracycline, doxycycline, and oxytetracycline) are excreted in an unchanged form in urine at a rate of more than 70%. They enter the aquatic environment in altered and unaltered forms which affect aquatic micro- and macroorganisms. This study reviews the occurrence, fate, and removal techniques of tetracycline contamination in Europe. The average level of tetracycline contamination in water ranged from 0 to 20 ng/L. However, data regarding environmental contamination by tetracyclines are still insufficient. Despite the constant presence and impact of tetracyclines in the environment, there are no legal restrictions regarding the discharge of tetracyclines into the aquatic environment. To address these challenges, various removal techniques, including advanced oxidation, adsorption, and UV treatment, are being critically evaluated and compared. The summarized data contributes to a better understanding of the current state of Europe\'s waters and provides insight into potential strategies for future environmental management and policy development. Further research on the pollution and effects of tetracyclines in aquatic environments is therefore required.
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  • 文章类型: Systematic Review
    背景:图拉西斯,Tularemia的病原体,在整个北半球都是地方性的,只需要10种生物就可以引起疾病,使这种潜在的生物恐怖主义剂成为已知的最具传染性的细菌病原体之一。氨基糖苷类,四环素,and,最近,氟喹诺酮类药物被用于治疗兔热病;然而,关于这些和其他抗菌类别的相对有效性的数据是有限的。
    方法:九个数据库,包括Medline,全球卫生,和Embase,系统地搜索了包含与tularemia相关术语的文章。有病例级数据的文章,抗菌治疗,并纳入患者预后。患者人口统计学,临床发现,抗菌药物管理,和结果(例如,插管,死亡率)使用标准化表格进行抽象。
    结果:在确定和筛选的8878种出版物中,描述1993年至2023年870例病例的410篇文章符合纳入标准。报告的病例来自35个国家;一半以上来自美国,土耳其,或者西班牙。最常见的临床形式是输尿管,口咽,腺体,和肺炎。在接受氨基糖苷类治疗的患者中(n=452[52%]),氟喹诺酮类药物(n=339[39%]),或四环素(n=419[48%]),死亡率为0.7%,0.9%,和1.2%,分别。与接受氨基糖苷类和四环素类药物的患者相比,接受环丙沙星的肺炎疾病患者没有死亡,胸腔穿刺术/胸腔积液引流和插管的发生率最低。
    结论:氨基糖苷类,氟喹诺酮类药物,四环素是治疗兔热病的有效抗菌药物,无论临床表现如何。特别是对于肺炎,与其他抗菌剂相比,环丙沙星可能有轻微的优势。
    Francisella tularensis, the causative agent of tularemia, is endemic throughout the Northern Hemisphere and requires as few as 10 organisms to cause disease, making this potential bioterrorism agent one of the most infectious bacterial pathogens known. Aminoglycosides, tetracyclines, and, more recently, fluoroquinolones are used for treatment of tularemia; however, data on the relative effectiveness of these and other antimicrobial classes are limited.
    Nine databases, including Medline, Global Health, and Embase, were systematically searched for articles containing terms related to tularemia. Articles with case-level data on tularemia diagnosis, antimicrobial treatment, and patient outcome were included. Patient demographics, clinical findings, antimicrobial administration, and outcome (eg, intubation, fatality) were abstracted using a standardized form.
    Of the 8878 publications identified and screened, 410 articles describing 870 cases from 1993 to 2023 met inclusion criteria. Cases were reported from 35 countries; more than half were from the United States, Turkey, or Spain. The most common clinical forms were ulceroglandular, oropharyngeal, glandular, and pneumonic disease. Among patients treated with aminoglycosides (n = 452 [52%]), fluoroquinolones (n = 339 [39%]), or tetracyclines (n = 419 [48%]), the fatality rate was 0.7%, 0.9%, and 1.2%, respectively. Patients with pneumonic disease who received ciprofloxacin had no fatalities and the lowest rates of thoracentesis/pleural effusion drainage and intubation compared to those who received aminoglycosides and tetracyclines.
    Aminoglycosides, fluoroquinolones, and tetracyclines are effective antimicrobials for treatment of tularemia, regardless of clinical manifestation. For pneumonic disease specifically, ciprofloxacin may have slight advantages compared to other antimicrobials.
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  • 文章类型: Journal Article
    背景:与战斗有关的伤口感染使受伤的军事人员的康复复杂化,导致总体发病率和死亡率。由于伤口的大小和深度,战斗环境中的伤口感染面临着独特的挑战,需要在现场管理紧急护理,以及军事设施后续治疗的需要。鉴于多重耐药病原体的增加,一本小说,当护理标准失效时,广谱抗生素在这种连续的护理中是需要的。Omadacycline于2018年获得FDA批准,用于治疗成人急性细菌性皮肤和皮肤结构感染(ABSSSI)。以及社区获得性细菌性肺炎(CABP)。它是一种具有抗革兰氏阳性活性的广谱抗生素,革兰氏阴性,和非典型细菌病原体,包括多重耐药物种。Omadacycline可以克服通常报道的四环素耐药机制,核糖体保护蛋白,和外排泵,并提供每日一次静脉或口服制剂。在这次审查中,我们讨论了奥马环素的潜在作用,包含在国防部的处方中,在战斗伤口感染的背景下。
    方法:对2023年7月21日之前发表的手稿进行了文献综述。这包括通过PubMed发现的一系列出版物,以及在ParatekPharmaceuticals上公开提供的参考书目,公司网站。以英文发表的与ESKAPEE有关的omadacycline的主要数据的出版物(屎肠球菌,金黄色葡萄球菌,肺炎克雷伯菌,鲍曼不动杆菌,铜绿假单胞菌,大肠杆菌,和肠杆菌)病原体和艰难梭菌,包括体外,在体内,并纳入临床资料。
    结果:在260条确定的记录中,66人被纳入证据审查。Omadacycline对几乎所有的ESKAPEE病原体具有体外活性,除了铜绿假单胞菌.重要的是,它对军事医疗系统中引起伤口感染的四种最常见的细菌病原体具有活性:金黄色葡萄球菌,包括耐甲氧西林金黄色葡萄球菌,A.鲍曼尼,肺炎克雷伯菌,和大肠杆菌。大鼠体内研究表明,奥马环素在大多数组织中迅速分布,骨矿物质中组织与血液的浓度比最高。已在ABSSSI(OASIS-1和OASIS-2)和CABP(OPTIC)患者的三项独立的3期研究中评估了omadacycline的临床疗效。总的来说,奥马环素在ABSSSI和CABP的治疗中具有既定的安全性。
    结论:奥马他环素具有广谱活性,口服给药的选择和既定的安全性,使其成为军事个人急救箱中莫西沙星的潜在有吸引力的替代品,尤其是考虑到对氟喹诺酮类药物的耐药性增加。有必要进行进一步的研究和临床评估,以支持在军事医疗系统中更广泛地使用omadacycline治疗战斗伤口感染。
    BACKGROUND: Combat-related wound infections complicate the recovery of wounded military personnel, contributing to overall morbidity and mortality. Wound infections in combat settings present unique challenges because of the size and depth of the wounds, the need to administer emergency care in the field, and the need for subsequent treatment in military facilities. Given the increase in multidrug-resistant pathogens, a novel, broad-spectrum antibiotic is desired across this continuum of care when the standard of care fails. Omadacycline was FDA-approved in 2018 for treatment of adults with acute bacterial skin and skin structure infections (ABSSSI), as well as community-acquired bacterial pneumonia (CABP). It is a broad-spectrum antibiotic with activity against gram-positive, gram-negative, and atypical bacterial pathogens, including multidrug-resistant species. Omadacycline can overcome commonly reported tetracycline resistance mechanisms, ribosomal protection proteins, and efflux pumps, and is available in once-daily intravenous or oral formulations. In this review, we discuss the potential role of omadacycline, which is included in the Department of Defense Formulary, in the context of combat wound infections.
    METHODS: A literature review was undertaken for manuscripts published before July 21, 2023. This included a series of publications found via PubMed and a bibliography made publicly available on the Paratek Pharmaceuticals, Inc. website. Publications presenting primary data published in English on omadacycline in relation to ESKAPEE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, and Enterobacter species) pathogens and Clostridioides difficile, including in vitro, in vivo, and clinical data were included.
    RESULTS: Of 260 identified records, 66 were included for evidence review. Omadacycline has in vitro activity against almost all the ESKAPEE pathogens, apart from P. aeruginosa. Importantly, it has activity against the four most prevalent bacterial pathogens that cause wound infections in the military healthcare system: S. aureus, including methicillin-resistant S. aureus, A. baumannii, K. pneumoniae, and E. coli. In vivo studies in rats have shown that omadacycline is rapidly distributed in most tissues, with the highest tissue-to-blood concentration ratios in bone mineral. The clinical efficacy of omadacycline has been assessed in three separate Phase 3 studies in patients with ABSSSI (OASIS-1 and OASIS-2) and with CABP (OPTIC). Overall, omadacycline has an established safety profile in the treatment of both ABSSSI and CABP.
    CONCLUSIONS: Omadacycline has broad-spectrum activity, the option to be orally administered and an established safety profile, making it a potentially attractive replacement for moxifloxacin in the military individual first aid kit, especially when accounting for the increasing resistance to fluoroquinolones. Further studies and clinical evaluation are warranted to support broader use of omadacycline to treat combat wound infections in the military healthcare system.
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  • 文章类型: Meta-Analysis
    大环内酯类抗生素和四环素类抗生素具有超出其微生物能力的一系列抗炎特性。尽管这些反生物药已经被广泛使用,长期安全状况是有限的。我们对随机临床试验(RCT)进行了系统评价和荟萃分析,比较了大环内酯类药物或四环素类药物与安慰剂,以提供长期安全性信息。我们从开始到2022年10月搜索了Medline和EMBASE,并确定了报告研究药物相关死亡的研究,严重不良事件(SAE),或提款率,以及每种药物的常见不良反应。计算相对风险(RR)和伤害所需数量(NNH)。在包括的52个RCT中,有3,151名多西环素参与者,2519名参与者服用米诺环素,3,049名参与者服用阿奇霉素,763名参与者服用克拉霉素,262名红霉素参与者,和100名参与者服用罗红霉素。没有与任何研究药物相关的死亡,SAE的发生率与任何药物中的安慰剂没有显着差异。强力霉素的总体戒断率略高于安慰剂(RR,1.30;95%CI,1.12-1.52)和米诺环素(RR,1.29;95%CI,1.15-1.46)。多西环素因不良事件引起的戒断率较高(RR,2.82;95%CI,1.88-4.22),米诺环素(RR,1.48;95%CI,1.09-1.98),和阿奇霉素(RR,1.53;95%CI,1.13-2.08)。胃肠道(GI)紊乱是每种药物最常见的可耐受不良反应。光敏性和皮疹是多西环素和米诺环素的第二常见病例。我们没有发现长期使用大环内酯类或四环素类药物2年与SAE风险增加相关的证据。本文受版权保护。保留所有权利。
    Macrolides and tetracyclines are antibiotics that have a range of anti-inflammatory properties beyond their microbial capabilities. Although these antibiotics have been in widespread use, the long-term safety profiles are limited. We performed a systematic review and meta-analysis of randomized clinical trials that compared macrolides or tetracyclines with placeboes to provide long-term safety information. We searched Medline and EMBASE from inception to October 2022 and identified studies that reported study drug-related death, serious adverse events (SAEs), or withdrawal rates, and common adverse effects of each drug. Relative risk (RR) and number needed to harm were calculated. Of the 52 randomized clinical trials included, there are 3151 participants on doxycycline, 2519 participants on minocycline, 3049 participants on azithromycin, 763 participants on clarithromycin, 262 participants on erythromycin, and 100 participants on roxithromycin. There was no death related to any study drugs and rates of SAE were not significantly different from placebo in any drug. Overall withdrawal rates were slightly higher than placebo in doxycycline (RR, 1.30; 95% CI, 1.12-1.52) and minocycline (RR, 1.29; 95% CI, 1.15-1.46). Withdrawal rates due to adverse events were higher in doxycycline (RR, 2.82; 95% CI, 1.88-4.22), minocycline (RR, 1.48; 95% CI, 1.09-1.98), and azithromycin (RR, 1.53; 95% CI, 1.13-2.08). Gastrointestinal disturbances are the most common tolerable adverse effects for every drug. Photosensitivity and rash are the second most common adverse effects for doxycycline and minocycline. We found no evidence that long-term use up to 2 years of macrolides or tetracyclines was associated with increased risk of SAEs.
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  • 文章类型: Meta-Analysis
    背景:布鲁氏菌病是一种人畜共患疾病,可以从动物传播给人类。布鲁氏菌病是由布鲁氏菌属细菌引起的,通常是通过接触受感染的动物传播的,未经巴氏杀菌的乳制品,或空气传播的病原体。四环素(四环素和强力霉素)是常用于治疗布鲁氏菌病的抗生素;然而,抗生素耐药性已成为一个主要问题。这项研究评估了耐四环素布鲁氏菌分离株的全球流行情况。
    方法:在Scopus进行了系统搜索,PubMed,WebofScience,和EMBASE使用相关关键词和医学主题词(MeSH)术语,直到2022年8月13日,确定相关研究进行荟萃分析。使用随机效应模型来估计阻力的比例。Meta回归分析,亚组分析,并对异常值和有影响的研究进行了检查。
    结果:对四环素和强力霉素的耐药率估计为0.017(95%置信区间[CI],0.009-0.035)和0.017(95CI,0.011-0.026),分别,基于1983年至2020年进行的51项研究。两种药物的耐药性均随时间增加(四环素:r=0.077,P=0.012;强力霉素:r=0.059,P=0.026)。
    结论:布鲁氏菌对四环素和多西环素的耐药率较低(1.7%),但随着时间的推移而增加。四环素和多西环素耐药性的增加凸显了需要进一步研究以了解耐药机制并开发更有效的治疗方法。
    BACKGROUND: Brucellosis is a zoonotic disease that can be transmitted from animals to humans. Brucellosis is caused by bacteria of the genus Brucella, which are typically transmitted through contact with infected animals, unpasteurized dairy products, or airborne pathogens. Tetracyclines (tetracycline and doxycycline) are antibiotics commonly used to treat brucellosis; however, antibiotic resistance has become a major concern. This study assessed the worldwide prevalence of tetracycline-resistant Brucella isolates.
    METHODS: A systematic search was conducted in Scopus, PubMed, Web of Science, and EMBASE using relevant keywords and Medical Subject Headings (MeSH) terms until August 13, 2022, to identify relevant studies for meta-analysis. A random effects model was used to estimate the proportion of resistance. Meta-regression analysis, subgroup analysis, and examination of outliers and influential studies were also performed.
    RESULTS: The prevalence rates of resistance to tetracycline and doxycycline were estimated to be 0.017 (95% confidence interval [CI], 0.009-0.035) and 0.017 (95%CI, 0.011-0.026), respectively, based on 51 studies conducted from 1983 to 2020. Both drugs showed increasing resistance over time (tetracycline: r = 0.077, P = 0.012; doxycycline: r = 0.059, P = 0.026).
    CONCLUSIONS: The prevalence of tetracycline and doxycycline resistance in Brucella was low (1.7%) but increased over time. This increase in tetracycline and doxycycline resistance highlights the need for further research to understand resistance mechanisms and develop more effective treatments.
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