intraperitoneal infection

腹腔感染
  • 文章类型: Journal Article
    这项研究的目的是研究头孢吡肟通过微透析向大鼠腹膜液中的渗透,并确定健康动物和通过盲肠结扎和穿孔引起的腹膜炎建立的败血症模型中未结合的药物血浆与组织浓度之间的关系。通过透析和反透析进行探针回收。头孢吡肟以110mg/kg的剂量静脉内给药。样品收集约4小时,和浓度通过液相色谱-电喷雾电离-QTOFMS测定。还测定了组织渗透。对照组和腹膜炎组的体内探针回收率分别为38.78%±3.31%和38.83%±2.74%,分别。头孢吡肟在两组腹腔液中分布较快。对照组和腹膜炎组的腹膜液/血浆头孢吡肟比率为0.38和0.32,分别。头孢吡肟浓度高于主要肠杆菌的4mg/L的MIC。所使用的感染模型对头孢吡肟在大鼠体内的药代动力学无明显影响。这是第一个确定健康大鼠和实验性腹膜炎大鼠腹膜液中游离头孢吡肟浓度的研究。
    The aim of this study was to investigate the penetration of cefepime into rat peritoneal fluid by microdialysis and to determine the relationship between unbound drug plasma and tissue concentration in healthy animals and in a sepsis model established through cecal ligation and puncture-induced peritonitis. Probe recovery was performed by dialysis and retrodialysis. Cefepime was administered at a dose of 110 mg/kg intravenously. Samples were collected for about 4 h, and concentrations were determined by liquid chromatography-electrospray ionization-QTOF MS. Tissue penetration was also determined. Probe recovery in vivo was 38.78% ± 3.31% and 38.83% ± 2.74% in the control and peritonitis groups, respectively. Cefepime was rapidly distributed in the peritoneal fluid in both groups. The peritoneal fluid/plasma cefepime ratio was 0.38 and 0.32 for the control and peritonitis groups, respectively. Cefepime concentrations were above the MIC of 4 mg/L for the main enterobacteria. The infection model that was used had no apparent effect on the pharmacokinetics of cefepime in rats. This was the first study to determine free cefepime concentrations in the peritoneal fluid of healthy rats and rats with experimental peritonitis.
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  • 文章类型: Review
    金黄色葡萄球菌(SA)是人类的重要病原体,可引起广泛的疾病,轻度皮肤感染,严重的骨髓炎到致命的肺炎,败血症和败血症。小鼠模型极大地促进了SA研究的发展。然而,由于小鼠和人类之间免疫系统的巨大差异,传统的小鼠研究不能预测人类的成功,在这种情况下,人源化小鼠(HM)可以在一定程度上克服这种限制。HM可用于研究由SA产生的人特异性毒力因子以及SA与人相互作用的机制。这篇综述概述了SA研究中使用的HM模型的最新进展。
    Staphylococcus aureus (S. aureus) is an important pathogen for humans and can cause a wide range of diseases, from mild skin infections, severe osteomyelitis to fatal pneumonia, sepsis, and septicemia. The mouse models have greatly facilitated the development of S. aureus studies. However, due to the substantial differences in immune system between mice and humans, the conventional mouse studies are not predictive of success in humans, in which case humanized mice may overcome this limitation to some extent. Humanized mice can be used to study the human-specific virulence factors produced by S. aureus and the mechanisms by which S. aureus interacts with humans. This review outlined the latest advances in humanized mouse models used in S. aureus studies.
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  • 文章类型: Journal Article
    I型干扰素受体敲除(IFNAR-/-)小鼠不能够产生完整的先天免疫应答,因此,这些小鼠通常被认为是评估新出现病毒的致病性。我们试图评估IFNAR-/-小鼠中新出现的野生型丝状病毒感染的致病性,因为使用免疫活性小鼠的丝状病毒模型需要适应小鼠的病毒株。我们通过鼻内(i.n.)或腹膜内(i.p.)途径用低剂量或高剂量的Lloviu病毒(LLOV)或Bombali病毒(BOMV)感染IFNAR-/-小鼠,并比较感染后早期和晚期时间点的病毒载量。无论LLOV剂量如何,在i.n.感染后均未检测到疾病迹象和病毒RNA。相比之下,在早期时间点,i.p.感染导致高剂量LLOV和BOMV组的病毒载量增加。低剂量LLOV和BOMV组在晚期时间点实现更高的病毒载量。然而,所有组的生存率均为100%,且无疾病迹象.总之,我们的结果表明,IFNAR-/-小鼠模型在研究LLOV和BOMV致病性方面的价值有限。
    Type I interferon receptor knockout (IFNAR-/-) mice are not able to generate a complete innate immune response; therefore, these mice are often considered to assess the pathogenicity of emerging viruses. We infected IFNAR-/- mice with a low or high dose of Lloviu virus (LLOV) or Bombali virus (BOMV) by the intranasal (IN) or intraperitoneal (IP) route and compared virus loads at early and late time points after infection. No signs of disease and no viral RNA were detected after IN infection regardless of LLOV dose. In contrast, IP infections resulted in increased viral loads in the high-dose LLOV and BOMV groups at the early time point. The low-dose LLOV and BOMV groups achieved higher viral loads at the late time point. However, there was 100% survival in all groups and no signs of disease. In conclusion, our results indicate a limited value of the IFNAR-/- mouse model for investigation of the pathogenicity of LLOV and BOMV.
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  • 文章类型: Journal Article
    背景:产志贺毒素的大肠杆菌(STEC)O157:H7和O104:H4菌株是食源性疾病的重要病原体,例如出血性结肠炎和溶血性尿毒症综合征,这是5岁以下儿童以及老年人肾衰竭和死亡的主要原因。
    方法:将天然大肠杆菌O157:H7和O104:H4脂多糖(LPS)在碱性条件下部分脱酰,以获得具有三酰化脂质A物种-Ac3-S-LPS控制的致热S-LPS。
    结果:用来自大肠杆菌O157:H7和O104:H4的Ac3-S-LPS抗原或其组合(双疫苗)以25至250µg的单剂量对BALB/c小鼠进行腹膜内免疫诱导高滴度的血清O特异性IgG(主要是IgG1),保护动物免受致死剂量的同源STEC菌株的腹膜内攻击(60-100%的存活率),并在体内鼠模型下减少了大肠杆菌O157:H7和O104:H4的肠道定植(单价Ac3-S-LPS为6-8倍,双疫苗为10倍)。
    结论:Di疫苗在小鼠中同时诱导针对两种高毒力人类STEC菌株的全身和肠道抗定植免疫。由于致病性大肠杆菌的大量血清型多样性,基于安全的Ac3-S-LPS产生多价STEC疫苗的可能性似乎特别有希望。
    BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) O157:H7 and O104:H4 strains are important causative agents of food-borne diseases such as hemorrhagic colitis and hemolytic-uremic syndrome, which is the leading cause of kidney failure and death in children under 5 years as well as in the elderly.
    METHODS: the native E. coli O157:H7 and O104:H4 lipopolysaccharides (LPS) were partially deacylated under alkaline conditions to obtain apyrogenic S-LPS with domination of tri-acylated lipid A species-Ac3-S-LPS.
    RESULTS: intraperitoneal immunization of BALB/c mice with Ac3-S-LPS antigens from E. coli O157:H7 and O104:H4 or combination thereof (di-vaccine) at single doses ranging from 25 to 250 µg induced high titers of serum O-specific IgG (mainly IgG1), protected animals against intraperitoneal challenge with lethal doses of homologous STEC strains (60-100% survival rate) and reduced the E. coli O157:H7 and O104:H4 intestinal colonization under an in vivo murine model (6-8-fold for monovalent Ac3-S-LPS and 10-fold for di-vaccine).
    CONCLUSIONS: Di-vaccine induced both systemic and intestinal anti-colonization immunity in mice simultaneously against two highly virulent human STEC strains. The possibility of creating a multivalent STEC vaccine based on safe Ac3-S-LPS seems to be especially promising due to a vast serotype diversity of pathogenic E. coli.
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  • 文章类型: Journal Article
    Different microorganisms can cause intraperitoneal infection. This study was to distinguish different microbial infections by urine analysis. Rats were intraperitoneally injected with Escherichia coli, Staphylococcus aureus, and Candida albicans, separately. Urine samples were collected from rats at 0, 12, 36 and 72 h after infection. Urinary proteins were profiled using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Compared with the control (without infection), a total of 69 differential proteins were identified in rats injected with E. coli. A total of 31 differences proteins were identified in rats injected with S. aureus. A total of 38 differential proteins were identified in rats injected with C. albicans. Urine proteome was different when rats were infected by different microorganisms, suggesting that urine may have the potential for differential diagnosis of different intraperitoneal infections.
    不同的微生物都可以引起腹腔感染,文中尝试利用尿液来区分不同的微生物感染。通过在大鼠腹腔内分别注射大肠杆菌、金黄色葡萄球菌和白色念球菌建立3种模型,收集感染后0、12、36、72 h的尿液,并使用液相色谱串联质谱技术 (LC-MS/MS) 对尿蛋白进行分析。与感染前相比,在大肠杆菌腹腔注射模型中共鉴定到69个差异蛋白,在金黄色葡萄球菌腹腔注射模型中共鉴定到31个差异蛋白,在白色念球菌腹腔注射模型中共鉴定到38个差异蛋白。结果表明,腹腔注射不同的微生物时尿蛋白质组不同,提示尿液可能对不同的腹腔感染有鉴别诊断的潜能。.
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  • 文章类型: Journal Article
    Apidaecins are cationic, proline-rich antimicrobial peptides originally isolated from honeybees and exhibit high Gram-negative activity by inhibiting bacterial protein translation. Pharmacokinetics of apidaecin derivative Api137 was studied using single and multiple intravenous or subcutaneous injections as well as continuous subcutaneous infusion and correlated to its efficacy in a lethal murine Escherichia coli infection model. Survival rates of infected CD-1 mice were monitored and Api137 and its metabolites were quantified in plasma of uninfected CD-1 mice and Sprague Dawley rats using reversed-phase chromatography coupled online to mass spectrometry. The highest Api137 plasma levels of 23 mg/L were obtained after a single intravenous injection of 20 mg/kg body weight, which declined fast over the next 120 min (half-life time < 30 min). In contrast, continuous subcutaneous infusion of a similar dose over an hour (19.2 mg/kg/h) lead to stable plasma levels of ∼6 mg/L, which was above the minimal inhibitory concentration against E. coli ATCC 25922 (4 mg/L). The increased exposure by continuous subcutaneous administration of Api137 at 19.2 mg/kg/h over 48 h improved efficacy in the murine intraperitoneal sepsis model with survival rates of 67% over 5 days compared to 33% after intravenous and subcutaneous administration in different dosing schemes. To the best of our knowledge, continuous subcutaneous infusion using osmotic pumps was successfully utilized for delivery of an antimicrobial peptide for the first time. Additionally, the potential of apidaecin analogs as novel antibiotics is demonstrated even in a scenario where the infection site is clearly separated from the route of administration.
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  • 文章类型: Journal Article
    Porcine mucin has been commonly used to enhance the infectivity of bacterial pathogens, including Acinetobacter baumannii, in animal models, but the mechanisms for enhancement by mucin remain relatively unknown. In this study, using the mouse model of intraperitoneal (i.p.) mucin-enhanced A. baumannii infection, we characterized the kinetics of bacterial replication and dissemination and the host innate immune responses, as well as their potential contribution to mucin-enhanced bacterial virulence. We found that mucin, either admixed with or separately injected with the challenge bacterial inoculum, was able to enhance the tissue and blood burdens of A. baumannii strains of different virulence. Intraperitoneal injection of A. baumannii-mucin or mucin alone induced a significant but comparable reduction of peritoneal macrophages and lymphocytes, accompanied by a significant neutrophil recruitment and early interleukin-10 (IL-10) responses, suggesting that the resulting inflammatory cellular and cytokine responses were largely induced by the mucin. Depletion of peritoneal macrophages or neutralization of endogenous IL-10 activities showed no effect on the mucin-enhanced infectivity. However, pretreatment of mucin with iron chelator DIBI, but not deferoxamine, partially abolished its virulence enhancement ability, and replacement of mucin with iron significantly enhanced the bacterial burdens in the peritoneal cavity and lung. Taken together, our results favor the hypothesis that iron at least partially contributes to the mucin-enhanced infectivity of A. baumannii in this model.
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  • 文章类型: Journal Article
    The single greatest barrier to studying the lifestyle of Neisseria meningitidis stems from its exquisite adaptation to life in humans, a specialization which prevents it from infecting other animals. This barrier to modeling meningococcal infection has been overcome by the provision of factors that allow the meningococci to overcome one or more aspects of host restriction, including the use of mice expressing receptors that allow mucosal colonization and/or the inclusion of serum factors that facilitate meningococcal replication during disseminated meningococcal disease. Here we discuss these advances, consider variables that influence the outcome of infection, and detail the technical requirements to establish robust and reproducible nasal colonization or sepsis. Once established, these models can then be used to study the meningococcal lifestyle and the immune response during infection, and to facilitate development of novel drug or vaccine-based approaches to intervene in meningococcal carriage and disease.
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  • 文章类型: Case Reports
    念珠菌是一种罕见的机会性酵母,以其对两性霉素B(AmB)的抗性而闻名。在所有由非白色念珠菌引起的感染中,约占19.3%。约1.7%的泌尿生殖系统念珠菌病病例是由念珠菌属的全部谱引起的。最常见于血液系统恶性肿瘤患者,尤其是当病人接受化疗时。念珠菌感染通常表现为真菌血症;然而,只有7.3%的患者会发生腹膜炎.此案例研究描述了一名具有免疫能力的女性患者,该患者在腹腔镜输卵管积水手术后由C.lusitaniae引起腹膜内感染。根据药敏试验,患者接受氟康唑治疗。在排空的假性囊肿后,口服和经阴道注射氟康唑。保守治疗导致患者病情暂时改善,假性囊肿减少。念珠菌在产生全身和局部感染方面与其他念珠菌非常相似-主要在受损患者中。它在对AmB产生抗性的能力方面也是独特的。正确识别和快速使用正确的抗真菌药物进行选择性治疗对于成功治疗感染患者至关重要。手术应始终被视为最终的治疗选择。
    Candida lusitaniae is a rare opportunistic yeast which is known for its resistance to amphotericin B (AmB). It is responsible for about 19.3% of all infections caused by non-Candida albicans species, and for about 1.7% of all cases of genitourinary candidiasis brought about by the entire spectrum of Candida species. Most commonly it occurs in patients with hematologic malignancies, especially when a patient is receiving chemotherapy. Candida lusitaniae infection usually presents with fungemia; however, only 7.3% of all patients will develop peritonitis. This case study describes an immunocompetent female patient with an intraperitoneal infection caused by C. lusitaniae after laparoscopic hydrosalpinx surgery. The patient was treated with fluconazole according to susceptibility testing. Fluconazole was implemented both orally and by transvaginal injection into the space after the evacuated pseudocyst. Conservative treatment resulted in a temporary improvement of the patient\'s condition and a reduction of the pseudocyst. Candida lusitaniae is very similar to other Candida species in generating systemic and local infections - mainly in compromised patients. It is also unique in its ability to develop resistance to AmB. Proper identification and quick implementation of selective therapy with the right anti-fungal drug are crucial for successfully treating infected patients. Surgery should always be considered as a final treatment option.
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  • 文章类型: Journal Article
    目的通过微透析研究氨曲南(ATM)和阿维巴坦(AVI)在大鼠腹腔内液和肌肉间质液中的分布,有或没有腹膜炎,并将组织中未结合的浓度与血液中未结合的浓度进行比较。将微透析探针插入颈静脉,后腿肌肉,对照大鼠(n=5)和盲肠结扎和穿刺诱导的腹腔脓毒症大鼠(n=9)的腹膜腔。通过药物反透析测定每只大鼠中两种分子在每种培养基中的ATM和AVI探针回收率。ATM-AVI组合以100-25mg·kg-1的剂量作为静脉推注给药,在120分钟内收集微透析样品,和ATM-AVI浓度通过液相色谱-串联质谱法测定。进行非房室药代动力学分析,并使用非参数检验进行组(感染与对照组)和培养基之间的统计比较。在对照大鼠和腹膜炎大鼠中,ATM和AVI在腹膜内液体和肌肉中的分布迅速而完整,以及血液中的浓度分布,腹腔积液,肌肉几乎叠加在一起,在控制和感染的动物中,ATM和AVI。在对照和感染的动物中,未结合的组织细胞外液和曲线下的全身面积之间没有观察到统计学上的显着差异。在本研究中,盲肠结扎穿刺术诱导的腹腔感染对大鼠ATM和AVI的药代动力学无明显影响。
    The purpose of this study was to investigate aztreonam (ATM) and avibactam (AVI) distribution in intraperitoneal fluid and muscle interstitial fluid by microdialysis in rats, with or without peritonitis, and to compare the unbound concentrations in tissue with the unbound concentrations in blood. Microdialysis probes were inserted into the jugular veins, hind leg muscles, and peritoneal cavities of control rats (n = 5) and rats with intra-abdominal sepsis (n = 9) induced by cecal ligation and punctures. ATM and AVI probe recoveries in each medium were determined for both molecules in each rat by retrodialysis by drug. ATM-AVI combination was administered as an intravenous bolus at a dose of 100-25 mg · kg-1 Microdialysis samples were collected over 120 min, and ATM-AVI concentrations were determined by liquid chromatography-tandem mass spectrometry. Noncompartmental pharmacokinetic analysis was conducted and nonparametric tests were used for statistical comparisons between groups (infected versus control) and medium. ATM and AVI distribution in intraperitoneal fluid and muscle was rapid and complete both in control rats and in rats with peritonitis, and the concentration profiles in blood, intraperitoneal fluid, and muscle were virtually superimposed, in control and infected animals, both for ATM and AVI. No statistically significant difference was observed between unbound tissue extracellular fluid and systemic areas under the curve for both molecules in control and infected animals. In the present study, intraperitoneal infection induced by cecal ligation and puncture had no apparent effect on ATM and AVI pharmacokinetics in rats.
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