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Sensitivity to antibacterial drugs of biofilms formed by strains of vibrio cholerae of various serogroups. 不同血清群霍乱弧菌菌株形成的生物膜对抗菌药物的敏感性。
Pub Date : 2023-04-29 DOI: 10.37489/0235-2990-2023-68-1-2-16-21
N. Selyanskaya, S. Titova, E. Menshikova, V. D. Kruglikov, M. I. Yezhova
The ability of Vibrio cholerae to form biofilms may cause ineffectiveness of cholera treatment and prevention. The aim of the study was to determine the antibiotic sensitivity of V.cholerae in biofilms. Material and methods. Sensitivity to 11 antibacterial agents was determined for biofilms of 10 strains of V.cholerae of different serogroups isolated from humans and from water obtained for 48 hours at 37°C on plastic plates in vials with autoclaved tap water infected with a suspension of 104 V.cholerae microbial cells. For this purpose the plates were washed three times in physiological solution and transferred into penicillin vials with double dilutions of antibacterial agents in liquid nutrient medium (Martin's broth, pH 7.7). After 24 hours of cultivation in the thermostat (37°C), the biofilms were imprinted and 0.1 ml of plankton culture was seeded onto plates with Marten's agar (pH 7.7). After 24 hours in the thermostat (37°C), the biofilms were imprinted and 0.1 ml of plankton culture was sown on plates with Marten's agar (pH 7.7). The result was counted after 24 h, determining the minimum suppressive concentrations of preparations by the presence or absence of V.cholerae growth. Results. The strains studied in biofilm communities, in contrast to the planktonic form, were highly resistant to all antibacterial drugs taken in the study, except for ciprofloxacin and ceftazidime. To improve the effectiveness of treatment of cholera and other infections whose causative agents are cholera vibrio, it is necessary to determine the antibiotic sensitivity of V.cholerae biofilms.
霍乱弧菌形成生物膜的能力可能导致霍乱治疗和预防的无效。本研究的目的是确定霍乱弧菌在生物膜中的抗生素敏感性。材料和方法。从人体和水中分离的10株不同血清群霍乱弧菌的生物膜对11种抗菌剂的敏感性进行了测定,这些生物膜在塑料板上装瓶,在37°C条件下,用高压灭菌的自来水感染了104个霍乱弧菌微生物细胞悬浮液。为此,将培养皿在生理溶液中洗涤三次,然后用两倍稀释的抗菌剂在液体营养培养基(马丁氏肉汤,pH值7.7)中转移到青霉素瓶中。恒温箱(37℃)培养24小时后,印迹生物膜,将0.1 ml浮游生物培养液接种于pH为7.7的马腾琼脂培养皿上。恒温(37℃)24小时后,印迹生物膜,将0.1 ml浮游生物培养物播种在pH为7.7的马腾琼脂培养皿上。24 h后计数结果,通过有无霍乱弧菌生长来确定制剂的最低抑制浓度。结果。与浮游形式相比,在生物膜群落中研究的菌株对研究中使用的除环丙沙星和头孢他啶外的所有抗菌药物都具有高度耐药性。为了提高霍乱和其他以霍乱弧菌为病原体的感染的治疗效果,有必要确定霍乱弧菌生物膜的抗生素敏感性。
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引用次数: 0
Evaluation of the antimicrobial activity of pyrimidine compound 3-(2-benzyloxy-2-oxoethyl)quinazoline-4(3H)-oh in relation to Klebsiella pneumoniae 嘧啶类化合物3-(2-苄基氧基-2-氧乙基)喹唑啉-4(3H)-oh对肺炎克雷伯菌的抑菌活性评价
Pub Date : 2023-04-29 DOI: 10.37489/0235-2990-2023-68-1-2-22-26
A. B. S. Hmidet, A. Yasenyavskaya, A. Tsibizova, I. Tyurenkov, A. Ozerov, M. Samotrueva
The study is devoted to the evaluation of the antimicrobial activity against Klebsiella pneumoniae of the pyrimidine compound 3-(2-Benzyloxy-2-oxoethyl)quinazoline-4(3H)-one under in vivo conditions in a model of generalized infection. The experiment was performed on 40 CBA line mice, which were divided into four groups: Group 1, control animals that received intraperitoneal injection water in an equivalent volume (control I); Group 2, infected animals that received no treatment (control II); Group 3, mice with generalized infection that received ceftriaxone at a dose of 50 mg/kg intraperitoneally for 7 days as treatment; Group 4, infected animals that received the study compound at a dose of 31 mg/kg (1/10 of the molecular weight) for 7 days. Generalized infection was modeled by intraperitoneal injection of Cl. pneumoniae at a dose of 3×106 in a volume of 0.5 ml. In the course of the experiment, animal survival rate was evaluated. After the mice were removed from the experiment, the blood, liver, spleen and lungs were calculated, and the total number of leukocytes, C-reactive protein and procalcitonin were determined. The compound under study was found to increase the survival rate of laboratory animals under conditions of generalized Klebsiella infection, as well as to decrease the insemination index, the total number of leukocytes and the level of markers of generalized infection. Thus, the pyrimidine derivative 3-(2-Benzyloxy-2-oxoethyl)quinazolin-4(3H)-one exhibits antibacterial activity comparable to that of the reference drug — ceftriaxone against Klebsiella pneumoniae under experimental infection.
本研究致力于评价嘧啶化合物3-(2-苄基氧基-2-氧乙基)喹唑啉-4(3H)- 1在体内条件下对肺炎克雷伯菌的抗菌活性。实验选用40只CBA系小鼠,分为4组:1组为对照组,腹腔注射等量水(对照1);第2组,未接受治疗的感染动物(对照II);第3组,广泛性感染小鼠,以50 mg/kg剂量腹腔注射头孢曲松7天;第4组,感染动物以31 mg/kg(分子质量的1/10)的剂量接受研究化合物7天。通过腹腔注射Cl模拟全身性感染。以0.5 ml的体积给药3×106给药。在实验过程中,评估动物存活率。实验结束后,计算小鼠血、肝、脾、肺,并测定白细胞总数、c反应蛋白和降钙素原。本研究发现,该化合物能提高实验动物在广泛性克雷伯氏菌感染条件下的存活率,降低受精卵指数、白细胞总数和广泛性感染标志物水平。因此,嘧啶衍生物3-(2-苄基氧基-2-氧乙基)喹唑啉-4(3H)- 1在实验感染下对肺炎克雷伯菌的抗菌活性与对照药物头孢曲松相当。
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引用次数: 0
Rapid analysis of the effect of aminoglycosides on bacteria by using a sensor system based on a piezoelectric resonator with a lateral electric field 利用具有侧向电场的压电谐振器传感器系统快速分析氨基糖苷类对细菌的影响
Pub Date : 2023-04-29 DOI: 10.37489/0235-2990-2023-68-1-2-4-10
О. Guliy, B. Zaitsev, A. Alsowaidi, О. Karavaeva, A. Semyonov, I. Borodina
The possibility of express analysis of the effect of aminoglycoside antibiotics on bacteria (Escherichia coli) using a sensor system based on a piezoelectric resonator with a lateral electric field with an operating frequency range of 6–7 MHz is shown. E.coli strains, both sensitive and resistant to kanamycin were used for the experiments. During evaluating the kanamycin effect on bacteria, the change in the electrical impedance modulus of the resonator was used as an analitical signal. It has been established that the criterion for the antibiotic bacteria sensitivity is the change in the modulus of the sensor electrical impedance after antibiotic exposure on bacteria at any frequency near the resonance. The sensor is highly sensitive and allows diagnosing the antimicrobial susceptibility of bacteria within 7–9 minutes.
利用基于压电谐振器的传感器系统,在6-7 MHz的工作频率范围内,对氨基糖苷类抗生素对细菌(大肠杆菌)的影响进行快速分析的可能性。实验采用对卡那霉素敏感和耐药的大肠杆菌菌株。在评价卡那霉素对细菌的作用时,用谐振器电阻抗模量的变化作为分析信号。已经建立了抗生素细菌敏感性的判据是抗生素暴露于细菌在共振附近的任何频率后传感器电阻抗模量的变化。该传感器灵敏度高,可在7-9分钟内诊断出细菌的抗菌敏感性。
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引用次数: 1
The First Experience of Combined Use of Cefepime/Sulbactam and Aztreonam in ICU Patients with Nosocomial Infections Caused by Carbapenem-Resistant Gram-Negative Microorganisms Producing Class B and D Carbapenemases 头孢吡肟/舒巴坦与氨曲南联合应用于产生B、D类碳青霉烯酶的耐药革兰氏阴性微生物引起的ICU院内感染的首次体会
Pub Date : 2023-02-11 DOI: 10.37489/0235-2990-2022-67-11-12-36-45
M. Suvorova, I. Sychev, O. Ignatenko, E. Burmistrova, S. S. Mirzakhamidova, L. Fedina, R. Vakolyuk, S. Yakovlev
Background. The difficulties of antibacterial therapy of infections caused by carbapenemase-producing  gram-negative bacteria are associated with limited options for adequate therapy since, in addition to resistance to carbapenems and other beta-lactams, these microorganisms are often characterized by associated resistance to other classes of antibiotics, including polymyxins. In vitro data support the idea of combined use of inhibitor-protected cephalosporins with aztreonam for the treatment of such infections. The aim of the study was to investigate the effectiveness of cefepime/sulbactam (FEP/SB) in combination with aztreonam (ATM) in infections caused by class B and D carbapenemase producers.Methods. A prospective observational study evaluated the effectiveness of the combination of FEP/SB + ATM in ICU patients with nosocomial infections complicated by sepsis or septic shock caused by carbapenem-resistant pathogens with documented production of class B or D carbapenemase. The ineffectiveness of previous treatment and the absence of other options for adequate therapy were used as inclusion criteria. Microbiological, clinical efficacy, and 30-day mortality were indicators of therapy evaluation.Results. The study included 25 patients with nosocomial infection (76% of them was VAP), with sepsis (60%) or septic shock (40%) and an average SOFA score of 6 points caused by Klebsiella pneumoniae (23 patients) or Pseudomonas aeruginosa (2) producing carbapenemases OXA-48 (56%), NDM (20%), NDM + OXA-48 (16%), and class B carbapenemase in two strains of P. aeruginosa. The average daily dose of FEP/SB and ATM was 6.6 g, the duration of therapy was 9.9 days. As a result of the treatment, eradication was achieved in 68% of patients, clinical efficacy was 72%, and the 30-day mortality rate was 28%.Conclusion. Our results show good clinical and bacteriological efficacy of the combination of FEP/SB and ATM in infections caused by extremely resistant K. pneumoniae, non-susceptible to carbapenems and producing class B or D carbapenemase.
背景。产生碳青霉烯酶的革兰氏阴性菌引起的感染的抗菌治疗困难与适当治疗的选择有限有关,因为除了对碳青霉烯类和其他β -内酰胺类耐药外,这些微生物通常还伴有对其他类别抗生素的耐药,包括多粘菌素。体外数据支持联合使用抑制剂保护的头孢菌素与氨曲南治疗此类感染的想法。本研究旨在探讨头孢吡肟/舒巴坦(FEP/SB)联合氨曲南(ATM)治疗B类和D类碳青霉烯酶产生菌感染的疗效。一项前瞻性观察性研究评估了FEP/SB + ATM联合治疗由碳青霉烯类耐药病原菌引起的院内感染并脓毒症或感染性休克的ICU患者的有效性,这些病原菌有B类或D类碳青霉烯酶的产生。既往治疗无效和缺乏其他适当治疗方案被用作纳入标准。微生物学、临床疗效、30天死亡率是评价治疗效果的指标。该研究纳入了25例医院感染(76%为VAP),脓毒症(60%)或脓毒性休克(40%)患者,平均SOFA评分为6分,由肺炎克雷伯菌(23例)或铜绿假单胞菌(2例)引起,两株铜绿假单胞菌产生碳青霉烯酶OXA-48(56%)、NDM(20%)、NDM + OXA-48(16%)和B类碳青霉烯酶。FEP/SB和ATM的平均日剂量为6.6 g,治疗时间为9.9 d。经治疗,68%的患者根治,72%的患者临床有效率,30天死亡率为28%。本研究结果显示,FEP/SB联合ATM治疗极耐药肺炎克雷伯菌感染,对碳青霉烯类不敏感,产生B类或D类碳青霉烯酶,具有良好的临床和细菌学效果。
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引用次数: 0
Some Peculiarities of Modern Comorbid Tuberculosis Therapy 现代结核共病治疗的一些特点
Pub Date : 2023-02-11 DOI: 10.37489/0235-2990-2022-67-11-12-46-50
V. Kolomiets, A. Kovalenko, A. Petrov, E. Pavlenko, E. Talikova
The aim of the work was to study the effectiveness of remaxol inclusion in treatment regimens designed for patients with comorbid tuberculosis and hepatotoxic response to etiotropic therapy.Materials and Methods. Case histories of 25 patients (21 men and 4 women) with a confirmed diagnosis of tuberculosis infection and hepatotoxic reactions to etiotropic treatment were analyzed. Of these, 9 patients had a comorbid (TB/HIV) pathology and 16 patients had TB/HIV with concomitant diseases. To stop the signs of hepatotoxicity, all patients were prescribed with remaxol: 400 ml intravenously on alternate days (course No. 5), then 1 time per week (course No. 4). In addition to the standard clinical and laboratory examination, all patients underwent follow-up (before and after the course of remaxol) examination of the levels of aspartate aminotransferase and total bilirubin in the blood, as well as the levels of interleukin production (1β, 4, 6 and 10) and tumor necrosis factors (TNF-α and TNF-γ). Standard regimens were used when conducting anti-tuberculosis chemotherapy.Results. It was noted that the presence of a comorbidity aggravates the course of tuberculosis and reduces the effectiveness of etiotropic therapy due to the development of hepatotoxicity. The inclusion of remaxol contributed to a decrease in the severity of hepatotoxic reactions and made it possible to avoid the correction of the main treatment course. The revealed positive dynamic in cytokine profile indicators can be regarded as a mediated immunological effect of the drug and requires further research.
这项工作的目的是研究利马索纳入治疗方案的有效性,这些方案是为合并结核病和对致病因治疗有肝毒性反应的患者设计的。材料与方法。对25例确诊为结核感染的患者(男21例,女4例)的病例史和对致病因治疗的肝毒性反应进行分析。其中,9名患者有合并症(结核/艾滋病毒)病理,16名患者有结核/艾滋病毒伴发疾病。为了阻止肝毒性的迹象,所有患者都开了利马索:每隔一天静脉滴注400ml(疗程5),然后每周1次(疗程4)。除标准的临床和实验室检查外,所有患者随访(疗程前后)检查血中天冬氨酸转氨酶和总胆红素水平,以及白细胞介素生成(1β、4、6和10)和肿瘤坏死因子(TNF-α和TNF-γ)水平。抗结核化疗采用标准方案。值得注意的是,由于肝毒性的发展,合并症的存在加重了结核病的病程并降低了致病因治疗的有效性。纳入利马索有助于降低肝毒性反应的严重程度,并使其有可能避免纠正主要治疗过程。细胞因子谱指标显示的阳性动态可视为药物介导的免疫效应,有待进一步研究。
{"title":"Some Peculiarities of Modern Comorbid Tuberculosis Therapy","authors":"V. Kolomiets, A. Kovalenko, A. Petrov, E. Pavlenko, E. Talikova","doi":"10.37489/0235-2990-2022-67-11-12-46-50","DOIUrl":"https://doi.org/10.37489/0235-2990-2022-67-11-12-46-50","url":null,"abstract":"The aim of the work was to study the effectiveness of remaxol inclusion in treatment regimens designed for patients with comorbid tuberculosis and hepatotoxic response to etiotropic therapy.Materials and Methods. Case histories of 25 patients (21 men and 4 women) with a confirmed diagnosis of tuberculosis infection and hepatotoxic reactions to etiotropic treatment were analyzed. Of these, 9 patients had a comorbid (TB/HIV) pathology and 16 patients had TB/HIV with concomitant diseases. To stop the signs of hepatotoxicity, all patients were prescribed with remaxol: 400 ml intravenously on alternate days (course No. 5), then 1 time per week (course No. 4). In addition to the standard clinical and laboratory examination, all patients underwent follow-up (before and after the course of remaxol) examination of the levels of aspartate aminotransferase and total bilirubin in the blood, as well as the levels of interleukin production (1β, 4, 6 and 10) and tumor necrosis factors (TNF-α and TNF-γ). Standard regimens were used when conducting anti-tuberculosis chemotherapy.Results. It was noted that the presence of a comorbidity aggravates the course of tuberculosis and reduces the effectiveness of etiotropic therapy due to the development of hepatotoxicity. The inclusion of remaxol contributed to a decrease in the severity of hepatotoxic reactions and made it possible to avoid the correction of the main treatment course. The revealed positive dynamic in cytokine profile indicators can be regarded as a mediated immunological effect of the drug and requires further research.","PeriodicalId":8471,"journal":{"name":"Antibiotics and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76600731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development of a High-Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS) Method to Determine the Presence of Rivastigmine in Human Plasma in Clinical Studies of Comparative Pharmacokinetics 建立高效液相色谱-串联质谱(HPLC-MS/MS)测定人血浆中利瓦斯汀存在的比较药代动力学临床研究方法
Pub Date : 2023-02-11 DOI: 10.37489/0235-2990-2022-67-11-12-22-28
M. S. Dolov, L. Fishgoit, P. Sobolev, E. P. Tkach
The basis for conducting bioequivalence studies is the determination of the bioavailability of the active substance of the drug at its place of action by establishing the concentration of the drug in biological fluids using sensitive analytical techniques. The bioanalytical technique used should provide reliable results which would lead to satisfactory level of interpretation. To investigate the bioequivalence of rivastigmine preparations, an 8 times more sensitive method (compared to the data in the available literature) for the quantitative determination of rivastigmine in human blood plasma by HPLC-MS/MS was developed. Rivastigmine is extracted from plasma by precipitation of plasma proteins with acetonitrile. Chromatographic separation of rivastigmine and the internal standard was carried out on a YMC  Triart C18. 50×2.0 mm (1.9 µm) column in a gradient elution mode with a flow rate of 0.5 ml/min. A 0.1% solution of ammonium  hydroxide and acetonitrile were used as mobile phases. The lower limit of the quantitative determination of the method was 25 pg/ml.
进行生物等效性研究的基础是利用灵敏的分析技术确定药物在生物液中的浓度,从而确定药物的活性物质在其作用部位的生物利用度。所使用的生物分析技术应提供可靠的结果,从而导致令人满意的解释水平。为了研究利瓦斯汀制剂的生物等效性,建立了一种灵敏度比现有文献高8倍的人血浆中利瓦斯汀的HPLC-MS/MS定量测定方法。利瓦斯汀是用乙腈沉淀血浆蛋白从血浆中提取的。在YMC Triart C18上对利瓦斯汀和内标进行色谱分离。50×2.0 mm(1.9µm)柱,梯度洗脱模式,流速为0.5 ml/min。以0.1%的氢氧化铵和乙腈溶液为流动相。本方法的定量下限为25 pg/ml。
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引用次数: 0
Prospects for Phagоtherapy of Bacterial Infections Associated with the Provision of Medical Care 与提供医疗保健相关的细菌感染的吞噬治疗前景
Pub Date : 2023-02-11 DOI: 10.37489/0235-2990-2022-67-11-12-56-63
A. Daudova, R. O. Abdrakhmanova, A. Yasenyavskaya, Ju. Z. Demina, M. Rubalsky, O. V. Rubalsky, M. Samotrueva, O. Bashkina
Healthcare-associated infections (HAIs) are a global medical and socioeconomic problem. Nosocomial infections occupy one of the leading places among the causes of death in the Russian Federation. About 60–70% of all nosocomial infections are associated with the use of medical implants of various profiles. Pseudomonas aeruginosa, various types of streptococci, staphylococci, Escherichia coli, enterococci (Enterococcus faecalis), Klebsiella pneumoniae, Proteus mirabilis, and representatives of the genus Acinetobacter are highly  likely to be found  in biofilms of medical supplies. A distinctive feature of microbes that cause  HAIs is poly- or even  pan-resistance of microbes to recommended antimicrobials. The search  for methods and means to overcome is a priority task of modern medicine. Phage therapy seems to be one of the logical and promising ways to combat bacteria that are resistant to conventional therapy. The article outlines the advantages and disadvantages of phage therapy, provides an overview of the successful use of mono- and combined preparations of bacteriophages in the experiment and clinic, as well as modern directions for the use of bacteriophages not only for therapeutic, but also for prophylactic purposes, based on the latest achievements of genetic engineering and biotechnology.
医疗保健相关感染(HAIs)是一个全球性的医学和社会经济问题。医院感染是俄罗斯联邦死亡的主要原因之一。大约60-70%的医院感染与使用各种形状的医疗植入物有关。铜绿假单胞菌、各种类型的链球菌、葡萄球菌、大肠杆菌、肠球菌(粪肠球菌)、肺炎克雷伯菌、奇迹变形杆菌和不动杆菌属的代表菌极有可能出现在医疗用品的生物膜中。引起HAIs的微生物的一个显著特征是微生物对推荐的抗菌素具有多重甚至泛耐药。寻找克服疾病的方法和手段是现代医学的首要任务。噬菌体疗法似乎是一种合乎逻辑且有前途的方法来对抗对传统疗法有抗药性的细菌。本文概述了噬菌体治疗的优点和缺点,综述了噬菌体单制剂和联合制剂在实验和临床中的成功应用,以及基于基因工程和生物技术的最新成果,噬菌体不仅用于治疗,而且用于预防目的的现代方向。
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引用次数: 1
Study of the Activity of Antiviral Drugs Against the Causative Agent of Chikungunya Fever in Cell Culture 细胞培养中抗病毒药物对基孔肯雅热病原菌活性的研究
Pub Date : 2023-02-11 DOI: 10.37489/0235-2990-2022-67-11-12-10-15
S. Loginova, V. N. Schukina, S. Savenko, R. V. Sakharov, S. Borisevich
Сhikungunya  virus (CHIKV) is a member of the Flavivirus genus, Flaviviridae family. It belongs to the zoonotic arbovirus infections transmitted by mosquitoes of the genus Aedes. In humans, this flavivirus causes a disease known as Сhikungunya fever, etymologically related to yellow fever, dengue, West Nile, and Zika. There is no specific treatment for Сhikungunya fever, as there is no vaccine or preventive measures to date. A comparative analysis of the effectiveness of chemotherapy drugs, interferon inducers and two classes of interferon α-, β-, and γ-showed that interferon drugs effectively inhibit the reproduction of CHIKV in the Vero cell culture in a wide range of concentrations. Chemotherapy drugs Triazavirin® and Ingavirin®  did not affect the reproduction of CHIKV strain FN198/66 in Vero cell culture. Ribavirin® at a concentration of 100 µg/ml almost completely suppressed the reproduction of the CHIKV virus when the drug was introduced into the culture medium both before and after infection.
Сhikungunya病毒(CHIKV)是黄病毒科黄病毒属的一员。它属于由伊蚊属蚊子传播的人畜共患虫媒病毒感染。在人类中,这种黄病毒引起一种称为Сhikungunya热的疾病,在词源上与黄热病、登革热、西尼罗河病毒和寨卡病毒有关。由于迄今没有疫苗或预防措施,目前尚无针对Сhikungunya热的特殊治疗方法。对化疗药物、干扰素诱导剂和α-、β-、γ-两类干扰素的有效性进行了对比分析,结果表明干扰素药物在大范围浓度下均能有效抑制CHIKV在Vero细胞培养中的繁殖。化疗药物Triazavirin®和Ingavirin®不影响CHIKV菌株FN198/66在Vero细胞培养中的繁殖。在感染前后将浓度为100 μ g/ml的利巴韦林®引入培养基中,几乎完全抑制了CHIKV病毒的繁殖。
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引用次数: 0
Activity of Cefiderocol and Other New Antibiotics Against Extensively Drug-Resistant Klebsiella pneumoniae Strains 头孢地罗等新型抗生素对广泛耐药肺炎克雷伯菌的活性研究
Pub Date : 2023-02-11 DOI: 10.37489/0235-2990-2022-67-11-12-16-21
E. V. Karpova, D. Tapalski
Background. The spread of extensive drug-resistance among gram-negative bacteria calls for the search for antimicrobics with new mechanisms of actions.The aim was to assess susceptibility of extensively drug-resistant K. pneumoniae strains to cefiderocol and other new inhibitor-protected β-lactams, and to determine genetic mechanisms of antibiotic resistance.Methods. This study included 30 extensively drug-resistant K. pneumoniae strains collected in 2016–2021 from 4 regions of Belarus. Carbapenemase genes were detected by real-time PCR. Minimum inhibitory concentrations (MICs) for cefiderocol and other new antibiotics were assessed by microdilution method using the Sensititre system. Whole genome sequencing was performed for 2 resistant and 3 cefiderocol-susceptible strains. Genome assemblies and annotation were performed using UGENE v. 37.0 software. Nucleotide sequences were translated using CLC  Sequence Viewer v. 8.0 (QIAGEN) package. The PROVEAN software was used to assess amino asides substitutions and their influence on the functional activity of proteins.Results. KPC carbapenemase-producers were 4 strains, OXA-48 — 17, KPC+OXA-48 — 1, NDM — 7, OXA-48 + NDM — 1. All KPC-producers were susceptible to imipenem/relebactam and meropenem/vaborbactam. Resistance to ceftazidime-avibactam was noted in all NDM  producers and OXA-48+NDM  co-producer. The study has identified 9 cefiderocol-resistant strains. These were NDM and OXA-48-producers isolated from hospitalized patients with COVID-19 infection from 3 regions of Belarus. Resistant strains had functionally significant nonsynonymous  substitutions in the genes of TonB-dependent receptors for catecholate siderophores FepA (F472V, P64S) and Fiu (T92S).Conclusion. The study has shown high efficacy of new inhibitor-protected carbapenems and cephalosporins against certain types of carbapenemase-producers. Strains with mutational resistance to cefiderocol, an antibiotic not previously used in Belarus, have been identified.
背景。在革兰氏阴性菌中广泛传播的耐药性要求寻找具有新的作用机制的抗菌素。目的评估广泛耐药肺炎克雷伯菌对头孢地罗和其他新型抑制剂保护的β-内酰胺类药物的敏感性,并探讨耐药的遗传机制。本研究包括2016-2021年从白俄罗斯4个地区收集的30株广泛耐药肺炎克雷伯菌。实时荧光定量PCR检测碳青霉烯酶基因。应用Sensititre系统采用微量稀释法评估头孢地罗和其他新型抗生素的最低抑菌浓度(mic)。对2株耐药菌株和3株头孢醚敏感菌株进行全基因组测序。使用UGENE v. 37.0软件进行基因组组装和注释。使用CLC Sequence Viewer v. 8.0 (QIAGEN)软件包翻译核苷酸序列。利用PROVEAN软件对氨基酸取代及其对蛋白质功能活性的影响进行了评价。产生KPC碳青霉烯酶的菌株为4株,分别为OXA-48 - 17、KPC+OXA-48 - 1、NDM - 7、OXA-48 + NDM - 1。所有kpc生产者对亚胺培南/瑞巴坦和美罗培南/瓦波巴坦敏感。所有NDM生产者和OXA-48+NDM共同生产者均发现头孢他啶-阿维巴坦耐药。这项研究已经确定了9种对头孢醚耐药的菌株。这些是从白俄罗斯3个地区的COVID-19感染住院患者中分离出的NDM和oxa -48生产者。耐药菌株在儿茶酚类铁载体FepA (F472V, P64S)和Fiu (T92S)的tonb依赖受体基因上存在显著的非同义替换。研究表明,新型抑制剂保护的碳青霉烯类和头孢菌素对某些类型的碳青霉烯酶产生者有很高的疗效。已经发现了对头孢地罗(一种在白俄罗斯以前未使用过的抗生素)具有突变抗性的菌株。
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引用次数: 1
Antibacterial and Antimycotic Properties of Modified Carbon Sorbents 改性碳吸附剂的抗菌和抗真菌性能
Pub Date : 2023-02-11 DOI: 10.37489/0235-2990-2022-67-11-12-4-9
V. Dolgikh, L. P’yanova, A. V. Lavrenov, E. V. Naumkina, A. V. Sedanova, M. S. Delyagina, D. N. Ogurtsova
The aim  of the work was to study the biological activity  of modifiers and carbon  sorbent samples modified by them  in relation to some types of microorganisms.Material and  methods. The carbon  sorbent under  study  and the modified samples were obtained at the Center of New Chemical Technologies BIC. Glycolic acid, lactic acid, glycine, and glutamic acid were used as modifiers. Strains of Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae 418, Esherichia coli ATCC 25922, Candida albicans (clinical strain) were used as test cultures. The test sample was placed in the wells of a sterile plate, then a working suspension of the test culture was added in the amount of 2.0 ml until completely wet 1:1. The survival of microorganisms was determined by quantitative inoculation from each well of the «sample — microorganism» mixture on Petri dishes with simple nutrient agar using the sector crop method (Gold). The culture species were confirmed by studying their cultural, morphological, and biochemical properties.Results. The conducted studies have demonstrated high antibacterial and antimycotic activity of carbon  sorbent samples modified with hydroxyl acids  in relation to the most  common opportunistic pathogens of pyoinflammatory diseases of bacterial and fungal  nature  in comparison with the initial  sorbent sample. The carbon  sorbent modified with lactic  acid oligomer showed the highest antibacterial and antimycotic activity.Conclusion. High antibacterial and antimycotic activity  of carbon  sorbent samples modified with hydroxy  acids  and amino acids in relation to the most common opportunistic pathogens of pyoinflammatory diseases of bacterial and fungal nature  was established in comparison with the initial  sample of the sorbent. The carbon  sorbent sample modified with amino acids has a pronounced antibacterial effect against all studied bacterial test strains, but exhibits weak antimycotic properties. The use of modified carbon  sorbents is a promising direction for the application therapy of pyoinflammatory infections.
本研究的目的是研究改性剂及其改性后的碳吸附剂样品对某些微生物的生物活性。材料和方法。所研究的碳吸附剂和改性样品是在BIC新化工技术中心获得的。乙醇酸、乳酸、甘氨酸和谷氨酸作为改性剂。以金黄色葡萄球菌ATCC 25923、铜绿假单胞菌ATCC 27853、肺炎克雷伯菌418、大肠埃希氏菌ATCC 25922、白色念珠菌(临床菌株)为试验培养菌。将待测样品置于无菌板孔中,加入待测培养物的工作悬浮液,加入量为2.0 ml,至1:1完全湿润。采用扇形作物法(Gold)从培养皿上的“样品-微生物”混合物的每孔定量接种确定微生物的存活。通过对培养种的培养、形态和生化特性的研究,确定了培养种。所进行的研究表明,与初始吸附剂样品相比,羟基酸修饰的碳吸附剂样品对细菌和真菌性质的最常见的化脓性炎症性疾病的条件致病菌具有较高的抗菌和抗真菌活性。乳酸低聚物改性的碳吸附剂具有最高的抗菌和抗真菌活性。与吸附剂初始样品相比,经羟基酸和氨基酸修饰的碳吸附剂样品具有较高的抗菌和抗真菌活性,这些碳吸附剂与最常见的细菌性和真菌性热炎性疾病的条件致病菌有关。用氨基酸修饰的碳吸附剂样品对所有研究的细菌试验菌株都有明显的抗菌作用,但抗真菌性能较弱。改性碳吸附剂的应用是治疗热炎性感染的一个很有前途的方向。
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Antibiotics and Chemotherapy
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