Antimicrobial therapy

抗菌治疗
  • 文章类型: Case Reports
    非结核分枝杆菌是引起肺部和肺外疾病的原因。这些生物体通常具有多重耐药性,对这些病例的管理提出了治疗挑战。肺癌已成为全球普遍的挑战,在受影响的个体中死亡率很高。腺癌通过引起诊断和治疗挑战而在大多数患者中造成衰弱的结果。腺癌和鸟分枝杆菌复合物的伴随关联使预后恶化,从而在处理此类病例时面临挑战。我们提出了腺癌和肺分枝杆菌之间的罕见关联,使传统的治疗方案复杂化。在本报告中概述了针对两种使人衰弱的疾病之间的这种独特伴随关联的治疗的不同方法。
    Nontuberculous mycobacteria are responsible for causing pulmonary as well as extrapulmonary diseases. These organisms are often multidrug resistant and management of these cases poses a therapeutic challenge. Lung cancer has been a prevalent challenge globally with a high mortality rate in affected individuals. Adenocarcinoma poses debilitating outcomes in most patients by inflicting a diagnostic and therapeutic challenge. The concomitant association of adenocarcinoma and Mycobacterium avium complex worsens the prognosis causing a challenge in managing such cases. We present a rare association between adenocarcinoma and pulmonary Mycobacterium avium complex complicating the traditional therapeutic regime. A different approach in the administration of therapy for this unique concomitant association between two debilitating diseases is outlined in the presented report.
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  • 文章类型: Case Reports
    感染的肺气肿性大疱由于其稀有性和多样化的临床表现而提出了诊断挑战。我们报道了一名52岁女性慢性呼吸道症状,包括呼吸困难和干咳,坚持六个月。影像学研究揭示了感染的气肿性大疱的特征,包括具有空气-流体水平的大型厚壁腔和相关的实质压缩。生物质暴露史和微生物分析,分离出耐甲氧西林凝固酶阴性葡萄球菌(MRCoNS),进一步支持诊断。患者对多西环素和利奈唑胺的抗菌治疗反应良好。此案例强调了在管理复杂的呼吸系统疾病中考虑环境因素和多学科合作的重要性。需要进一步的研究来阐明感染的肺气肿性大疱的最佳管理策略。
    Infected emphysematous bullae of the lung present a diagnostic challenge due to their rarity and diverse clinical manifestations. We report the case of a 52-year-old female with chronic respiratory symptoms, including breathlessness and dry cough, persisting for six months. Imaging studies revealed characteristic features of infected emphysematous bullae, including large thick-walled cavities with air-fluid levels and associated parenchymal compression. Biomass exposure history and microbiological analysis, which isolated methicillin-resistant coagulase-negative Staphylococcus (MRCoNS), further supported the diagnosis. The patient responded well to antimicrobial therapy with doxycycline and linezolid. This case underscores the importance of considering environmental factors and multidisciplinary collaboration in managing complex respiratory conditions. Further research is warranted to elucidate optimal management strategies for infected emphysematous bullae of the lung.
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  • 文章类型: Journal Article
    牙周炎相关的口腔微生物菌群失调被认为是导致不良妊娠结局(APO)的原因。不孕症,女性生殖炎症。由于益生菌可以调节牙周炎和口腔微生物菌群失调,这项研究检查了益生菌细菌素的作用,Nisin,调节牙周炎引发的生殖微生物组和炎症。将24只8周龄BALB/cByJ雌性小鼠随机分为4个治疗组(对照组,感染,Nisin,和感染+乳酸链球菌素组),每组6只小鼠。一种多微生物(牙龈卟啉单胞菌,Denticola密螺旋体,连翘坦菌,核梭杆菌)牙周病小鼠模型用于评估该病对女性生殖系统的影响,专注于微生物组,局部炎症,和乳酸链球菌素在这种情况下的治疗潜力。此外,16sRNA测序用于评估微生物组的变化,RT-PCR用于评估炎性细胞因子的变化。在生殖器官中检测到牙周病原体DNA,在实验期结束时的心脏和主动脉中,感染组的口腔DNA尤其升高。与对照组相比,只有牙龈卟啉单胞菌在感染组的口腔和子宫中显著增高,在感染组的口腔中,连翘和带核F.感染和乳酸链球菌素治疗组牙龈卟啉单胞菌水平明显降低,T.连翘,与感染组相比,口腔中的F.由于在心脏和主动脉中也检测到牙周病原体DNA,这表明潜在的循环系统传播。多微生物感染通常会降低子宫中的微生物组多样性,已被Nisin治疗废除。多微生物感染组,与对照组相比,通常在所有生殖器官中都有较低的Firmicutes和较高的拟杆菌,类似的趋势在心脏中显现出来。然而,乳酸链球菌素治疗组和感染和乳酸链球菌素治疗组,与对照组或感染组相比,通常在生殖器官和心脏中具有较高的变形杆菌和较低的Firmicutes和拟杆菌。Nisin治疗还改变了生殖道中的微生物群落结构,使其处于不反映对照的新状态。牙周病,与对照组相比,引发了子宫和口腔中炎性细胞因子(IL-6,TNF-α)的增加,已被Nisin治疗废除。多微生物牙周病改变了生殖道的微生物分布,微生物组,和炎症状态。Nisin调节生殖道的微生物谱和微生物组,并减轻由牙周病引发的子宫炎症细胞因子升高。
    Periodontitis-related oral microbial dysbiosis is thought to contribute to adverse pregnancy outcomes (APOs), infertility, and female reproductive inflammation. Since probiotics can modulate periodontitis and oral microbiome dysbiosis, this study examined the effects of a probiotic bacteriocin, nisin, in modulating the reproductive microbiome and inflammation triggered by periodontitis. A total of 24 eight-week-old BALB/cByJ female mice were randomly divided into four treatment groups (control, infection, nisin, and infection+nisin group), with 6 mice per group. A polymicrobial (Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum) mouse model of periodontal disease was used to evaluate the effects of this disease on the female reproductive system, with a focus on the microbiome, local inflammation, and nisin\'s therapeutic potential in this context. Moreover, 16s RNA sequencing was used to evaluate the changes in the microbiome and RT-PCR was used to evaluate the changes in inflammatory cytokines. Periodontal pathogen DNA was detected in the reproductive organs, and in the heart and aorta at the end of the experimental period, and the DNA was especially elevated in the oral cavity in the infection group. Compared to the control groups, only P. gingivalis was significantly higher in the oral cavity and uterus of the infection groups, and T. forsythia and F. nucleatum were significantly higher in the oral cavity of the infection groups. The infection and nisin treatment group had significantly lower levels of P. gingivalis, T. forsythia, and F. nucleatum in the oral cavity compared with the infection group. Since periodontal pathogen DNA was also detected in the heart and aorta, this suggests potential circulatory system transmission. The polymicrobial infection generally decreased the microbiome diversity in the uterus, which was abrogated by nisin treatment. The polymicrobial infection groups, compared to the control groups, generally had lower Firmicutes and higher Bacteroidota in all the reproductive organs, with similar trends revealed in the heart. However, the nisin treatment group and the infection and nisin group, compared to the control or infection groups, generally had higher Proteobacteria and lower Firmicutes and Bacteroidota in the reproductive organs and the heart. Nisin treatment also altered the microbiome community structure in the reproductive tract to a new state that did not mirror the controls. Periodontal disease, compared to the controls, triggered an increase in inflammatory cytokines (IL-6, TNF-α) in the uterus and oral cavity, which was abrogated by nisin treatment. Polymicrobial periodontal disease alters the reproductive tract\'s microbial profile, microbiome, and inflammatory status. Nisin modulates the microbial profile and microbiome of the reproductive tract and mitigates the elevated uterine inflammatory cytokines triggered by periodontal disease.
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  • 文章类型: Journal Article
    抗生素用于治疗细菌感染的过度使用已引起严重的细菌耐药性,并成为全球范围内的公共健康威胁。期望开发新的抗生素递送系统作为促进抗感染治疗的有效抗菌策略。在这里,通过微流体的AgNP负载的N-[(2-羟基-3-三甲基铵)丙基]壳聚糖(HTCC)/透明质酸(HA)多孔微球(HHPM)已被开发为新型细菌感染微环境(IME)响应性抗生素递送系统,用于促进抗菌治疗。AgNP的释放可以明确地响应于具有酸性pH值和相对高的透明质酸酶浓度的IME。HHPMs独特的多孔结构可以有效促进细菌的捕获和富集,从而发挥协同抗菌作用,这可以更有效地抑制和杀死即时细菌。通过研究HHPM的溶血活性和细胞毒性,揭示了HHPM的优异生物相容性。体内测定表明,制备的负载AgNP的HHPM可以有效地抵抗细菌感染,并通过抑制细菌存活来促进感染伤口部位的伤口愈合和组织再生。这项工作表明,制造的HHPM是用于抗生素递送的理想的细菌感染微环境响应材料,并显示出在临床上促进抗感染治疗的巨大前景。
    The overuse of antibiotics for treating bacterial infection has caused severe bacterial resistance and become a public health threat worldwide. It is desired to develop novel antibiotic delivery systems as efficient antibacterial strategies for promoting anti-infective therapy. Herein, the AgNPs-loaded N-[(2-hydroxy-3-trimethyl ammonium) propyl] chitosan (HTCC)/hyaluronic acid (HA) porous microspheres (HHPMs) by microfluidics have been developed as novel bacterial infection microenvironment (IME)-responsive antibiotic delivery systems for promoting antimicrobial therapy. The release of AgNPs can respond explicitly to the IME with acidic pH values and relatively high hyaluronidase concentration. The unique porous structures of HHPMs can effectively facilitate the capture and enrichment of bacteria, thus exerting synergistic antibacterial effects, which can be more efficient in instant bacteria inhibiting and killing. The excellent biocompatibility of HHPMs is revealed by investigating their hemolytic activity and cytotoxicity. In vivo assays demonstrate that the fabricated AgNPs-loaded HHPMs can effectively resist bacterial infection and promote wound healing and tissue regeneration at infected wound sites by inhibition of the bacterial survival. This work indicates that fabricated HHPMs are ideal bacterial infection microenvironment-responsive materials for antibiotic delivery and show great promises for promoting anti-infective therapy in clinics.
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  • 文章类型: Journal Article
    为应对因鱼类消费需求增加和随后的过度拥挤而导致的养鱼场细菌性疾病风险增加,目前,研究人员正在研究二甲酚酸(OA)治疗鱼类细菌感染的疗效和残留管理.这项研究对于全面了解OA的药代动力学至关重要。本研究调查了OA在幼年虹鳟鱼中的药代动力学。通过饲料给鱼服用12mgkg-1剂量的OA,收集肝脏的组织样本,肾,吉尔,肠,肌肉,和使用LC-MS/MS分析的血浆在g(4096.55μgkg-1)和肠道(11592.98μgkg-1)中发现了最高浓度的药物,在肝脏(0.36L/h)和g(0.07L/h)中也观察到显着的吸收(p<0.05)。发现肝脏(0.21L/h)和肾脏(0.03L/h)在消除药物方面最有效(p<0.05)。该研究还证实了该药物对几种细菌病原体的抗菌效果,包括厦门希瓦氏菌(0.25μgmL-1),链球菌(1μgmL-1),和水金黄杆菌(4μgmL-1)。该研究得出了不同鱼类组织之间的显着差异,在肾脏和肠道中观察到更高的浓度和更长的半衰期。针对主要细菌病原体的最低MIC值表明了其在水产养殖中的治疗潜力。它还强调了了解OA药代动力学以优化水产养殖中抗微生物治疗的重要性。
    In response to the heightened risk of bacterial diseases in fish farms caused by increased demand for fish consumption and subsequent overcrowding, researchers are currently investigating the efficacy and residue management of oxolinic acid (OA) as a treatment for bacterial infections in fish. This research is crucial for gaining a comprehensive understanding of the pharmacokinetics of OA. The present study investigates pharmacokinetics of OA in juvenile rainbow trout. The fish were given a 12 mg kg-1 dose of OA through their feed, and tissue samples were collected of the liver, kidney, gill, intestine, muscle, and plasma for analysis using LC-MS/MS. The highest concentrations of the drug were found in the gill (4096.55 μg kg-1) and intestine (11592.98 μg kg-1), with significant absorption also seen in the liver (0.36 L/h) and gill (0.07 L/h) (p < 0.05). The liver (0.21 L/h) and kidney (0.03 L/h) were found to be the most efficient (p < 0.05) at eliminating the drug. The study also confirmed the drug antimicrobial effectiveness against several bacterial pathogens, including Shewanella xiamenensis (0.25 μg mL-1), Lactococcus garvieae (1 μg mL-1), and Chryseobacterium aquaticum (4 μg mL-1). The study concludes significant variations among different fish tissues, with higher concentrations and longer half-lives observed in the kidney and intestine. The lowest MIC value recorded against major bacterial pathogens demonstrated its therapeutic potential in aquaculture. It also emphasizes the importance of understanding OA pharmacokinetics to optimize antimicrobial therapy in aquaculture.
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  • 文章类型: Letter
    暂无摘要。
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  • 文章类型: Journal Article
    在药代动力学改变的人群中,监测抗生素血浆水平至关重要,例如新生儿或成人重症监护病房的危重病人。本研究旨在开发和验证一种快速、可重复和灵敏的液相色谱-串联质谱测定(LC-MS/MS),用于测量阿莫西林的总浓度和未结合浓度,氨苄青霉素,头孢他啶,头孢曲松,厄他培南,人血浆中的磷霉素和青霉素G。该方法需要20和250μl样品体积来测量总浓度和未结合浓度,分别。样品制备包括蛋白沉淀和添加内标。超滤分离未结合的药物。方法验证涵盖选择性,结转,线性度准确度,精度,稀释效应,基体效应和稳定性。LC-MS/MS在7.5分钟的运行时间内进行。头孢他啶和厄他培南的校准曲线呈线性关系(范围为0.1-50和0.05-100mg/l,分别)和其他分析物的二次分析(0.1-50毫克/升,氨苄青霉素除外:0.1-20mg/l;R2>0.990)。准确度在标称浓度的±15%内,精密度不超过±15%(相对标准偏差)。样品在测试的温度和时间点没有显示出显著的降解。在危重新生儿中证明了临床适用性。该方法具有最小的样品体积和较短的分析时间,可以测量所选抗生素的总浓度和未结合浓度。适用于常规临床护理和研究。
    Monitoring antibiotic plasma levels is critical in populations with altered pharmacokinetics, such as critically ill patients in neonatal or adult intensive care units. This study aimed to develop and validate a rapid, reproducible and sensitive liquid chromatography-tandem mass spectrometry assay (LC-MS/MS) for measuring total and unbound concentrations of amoxicillin, ampicillin, ceftazidime, ceftriaxone, ertapenem, fosfomycin and penicillin G in human plasma. The method required 20 and 250 μl sample volumes for measuring total and unbound concentrations, respectively. Sample preparation involved protein precipitation and the addition of an internal standard. Ultrafiltration separated unbound drugs. Method validation covered selectivity, carryover, linearity, accuracy, precision, dilution effects, matrix effects and stability. The LC-MS/MS was performed within a run time of 7.5 min. Calibration curves were linear for ceftazidime and ertapenem (ranges 0.1-50 and 0.05-100 mg/l, respectively) and quadratic for other analytes (0.1-50 mg/l, except for ampicillin: 0.1-20 mg/l; R2 > 0.990). Accuracy was within ±15% of the nominal concentration, and precision did not exceed ±15% (relative standard deviation). Samples showed no significant degradation at the tested temperatures and time points. Clinical applicability was demonstrated in a critically ill neonate. This method with minimal sample volume and short analysis time enables the measurement of total and unbound concentrations of selected antibiotics, and is suitable for routine clinical care and studies.
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  • 文章类型: Journal Article
    急性胆管炎(AC)的标准治疗持续时间包括胆道引流后4-7天的抗菌治疗;然而,最近的研究表明,≤2-3天就足够了。然而,临床实践通常取决于体温作为停止抗菌治疗的标准。因此,在这项研究中,我们评估了AC患者是否可以通过≤7天的抗菌治疗获得成功的结果,即使发烧,假设感染源得到有效控制。我们进行了一项单中心回顾性研究,涉及AC患者,根据《2018年东京指南》定义的任何原因,成功进行胆道引流并完成≤7天抗菌治疗的患者.在完成抗菌治疗前24小时内,根据患者的体温将患者分为发热组和发热组。主要结果是临床治愈率,定义为在胆道引流后第14天没有出现初始症状,到第30天没有复发或死亡。次要结果是3个月的复发率。使用具有治疗加权的逆概率的逻辑回归。总的来说,408名患者被选中,其中40人(9.8%)发热。两组在临床治愈率和3个月复发率方面无明显差异。值得注意的是,限于抗生素治疗持续时间≤3天的患者的亚组在这些结局上也没有差异.因此,我们的结果表明,在最初计划的治疗期内停用抗生素足以成功引流AC。无论患者在终止妊娠前的24小时内的发烧状态如何。
    The standard treatment duration for acute cholangitis (AC) involves a 4-7-day antimicrobial treatment post-biliary drainage; however, recent studies have suggested that a ≤ 2-3 days is sufficient. However, clinical practice frequently depends on body temperature as a criterion for discontinuing antimicrobial treatment. Therefore, in this study, we assessed whether patients with AC can achieve successful outcomes with a ≤ 7-day antimicrobial treatment, even with a fever, assuming the infection source is effectively controlled. We conducted a single-center retrospective study involving patients with AC, defined following the Tokyo Guidelines 2018 for any cause, who underwent successful biliary drainage and completed a ≤ 7-day antimicrobial treatment. Patients were categorized into the febrile and afebrile groups based on their body temperature within 24 h before completing antimicrobial treatment. The primary outcome was the clinical cure rate, defined as no initial presenting symptoms by day 14 post-biliary drainage without recurrence or death by day 30. The secondary outcome was a 3-month recurrence rate. Logistic regression with inverse probability of treatment weighting was used. Overall, 408 patients were selected, among whom 40 (9.8%) were febrile. The two groups showed no significant differences in the clinical cure and 3-month recurrence rates. Notably, the subgroups limited to patients with a ≤ 3-day antibiotic treatment duration also showed no differences in these outcomes. Therefore, our results suggest that discontinuing antibiotics within the initially planned treatment period was sufficient for successful drainage cases of AC, regardless of the patient\'s fever status during the 24 h leading up to termination.
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  • 文章类型: Journal Article
    几乎没有证据表明通过治疗性血浆置换(TPE)消除抗微生物剂,也没有关于TPE患者抗微生物剂最佳剂量的指南。我们旨在评估TPE期间有关抗菌药物管理的当前实践和知识。2023年5月至11月进行了结构化的在线调查,并通过国家科学平台和专业协会邀请医生参加。一百零五名参与者完成了调查,其中61%是传染病医生,68.6%的人有十年以上的经验。74.3%的受访者报告说,TPE程序可以显着影响抗菌药物的血浆浓度。在医生中,42.9%建议调整抗菌药物剂量,38.1%的人建议在TPE期间暂时停止抗菌药物管理。33.3%的受访者建议对某些抗菌药物进行治疗药物监测,主要是糖肽和氨基糖苷类,同时接受TPE的患者。此外,59.3%的医生有时会咨询其他医疗保健专业人员进行治疗管理,最常见的是药剂师或临床药剂师和传染病专家。关于潜在药物的核心问题-,不到一半的医生通过TPE对与手术和患者相关的抗菌消除因子做出了准确的反应。很明显,缺乏关于TPE期间抗菌管理的临床实践和知识。为了确保抗菌药物的治疗效果,避免治疗失败,医师应改进他们的实践策略,并在这种数据不足的情况下考虑TPE消除抗菌药物的因素.
    There is little evidence of antimicrobial elimination via therapeutic plasma exchange (TPE) and no guidelines for antimicrobial optimal dosing in patients undergoing TPE. We aimed to assess current practices and knowledge regarding antimicrobial management during TPE. A structured online survey was conducted from May to November 2023, and physicians were invited to participate through national scientific platforms and professional societies. One hundred five participants completed the survey, of whom 61% were infectious disease physicians, with 68.6% having more than 10 years of experience. That the TPE procedure could significantly affect plasma concentrations of antimicrobial agents was reported by 74.3% of the respondents. Among the physicians, 42.9% suggest antimicrobial dose adjustment, and 38.1% recommend temporarily discontinuing antimicrobial drug administration during TPE. Therapeutic drug monitoring was recommended by 33.3% of the respondents for certain antimicrobials, mainly glycopeptides and aminoglycosides, in patients undergoing concurrent TPE. Furthermore, 59.3% of physicians sometimes consult with another healthcare professional for treatment management, most commonly a pharmacist or a clinical pharmacist and an infectious diseases specialist. The core questions regarding potential drug-, procedure-, and patient-related antimicrobial elimination factors via TPE were responded to accurately by less than half of the physicians. It was clear that they had a lack of clinical practices and knowledge regarding antimicrobial management during TPE. To ensure the therapeutic efficacy of antimicrobials and avoid treatment failure, physicians should improve their practice strategies and consider antimicrobial elimination factors with TPE in this data-poor setting.
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  • 文章类型: Journal Article
    急性胆囊炎是最常见的外科疾病之一。可能会从轻度进展到重度。当合并菌血症时,急性胆囊炎的死亡率高达10-20%。急性胆囊炎患者的护理标准是早期腹腔镜胆囊切除术。经皮胆囊造口术或内镜手术是选择性病例的替代疗法。然而,抗生素治疗在预防手术并发症和限制全身炎症反应方面发挥着关键作用,尤其是中度至重度胆囊炎患者。急性胆囊炎患者的胆汁细菌定植率为35-60%。最常见的微生物是大肠杆菌,克雷伯菌属。,链球菌属。,肠球菌属。,和梭菌属。早期经验性抗菌治疗以及感染源控制是成功治疗的基石。在这些情况下,抗生素的选择必须考虑一些因素(例如,临床表现的严重程度,如果在医院或社区获得感染的发作,药物渗入胆汁,和任何抗药性)。此外,在严重胆囊炎的情况下,必须根据胆汁培养物修改治疗方法。抗生素管理是正确处理胆汁相关感染的关键。有必要了解适当的治疗方案及其确切的持续时间。适当使用抗生素至关重要,应将其纳入良好的临床实践和护理标准。
    Acute cholecystitis is one of the most common surgical diseases, which may progress from mild to severe cases. When combined with bacteremia, the mortality rate of acute cholecystitis reaches up to 10-20%. The standard of care in patients with acute cholecystitis is early laparoscopic cholecystectomy. Percutaneous cholecystostomy or endoscopic procedures are alternative treatments in selective cases. Nevertheless, antibiotic therapy plays a key role in preventing surgical complications and limiting the systemic inflammatory response, especially in patients with moderate to severe cholecystitis. Patients with acute cholecystitis have a bile bacterial colonization rate of 35-60%. The most frequently isolated microorganisms are Escherichia coli, Klebsiella spp., Streptococcus spp., Enterococcus spp., and Clostridium spp. Early empirical antimicrobial therapy along with source control of infection is the cornerstone for a successful treatment. In these cases, the choice of antibiotic must be made considering some factors (e.g., the severity of the clinical manifestations, the onset of the infection if acquired in hospital or in the community, the penetration of the drug into the bile, and any drug resistance). Furthermore, therapy must be modified based on bile cultures in cases of severe cholecystitis. Antibiotic stewardship is the key to the correct management of bile-related infections. It is necessary to be aware of the appropriate therapeutic scheme and its precise duration. The appropriate use of antibiotic agents is crucial and should be integrated into good clinical practice and standards of care.
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