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Inhibition of S. aureus biofilm formation by linezolid alleviates sepsis-induced lung injury caused by S. aureus infection through direct inhibition of icaA activity. 利奈唑胺对金黄色葡萄球菌生物膜形成的抑制通过直接抑制icaA活性减轻由金黄色葡萄菌感染引起的败血症诱导的肺损伤。
IF 1.8 4区 医学 Q2 Medicine Pub Date : 2023-09-01
Huan Kuang, Hongxia Bi, Xiaoran Li, Xiaojv Lv, Yanbin Liu

Antibiotic-resistant S. aureus infections can be life-threatening. Linezolid is known to hinder S. aureus biofilm formation, but the underlying molecular mechanism remains unclear. Molecular docking revealed that linezolid can bind to icaA, and this was confirmed by thermal drift assays. Linezolid demonstrated a dose-dependent inhibition of icaA enzyme activity. Mutating Trp267, a key residue identified through molecular docking, significantly decreased linezolid binding and inhibitory effects on mutant icaA activity. However, the mutant icaA Trp267Ala showed only slight activity reduction compared to icaA. Linezolid had minimal impact on icaB's thermal stability and activity. The 50S ribosomal L3ΔSer145 mutant S. aureus exhibited similar growth and biofilm formation to the wild-type strain. Linezolid effectively suppressed the growth and biofilm formation of wildtype S. aureus. Although linezolid lost its ability to inhibit the growth of the mutant strain, it still effectively hindered its biofilm formation. Linezolid exhibited weaker attenuation of sepsis-induced lung injury caused by 50S ribosomal L3ΔSer145 mutant S. aureus compared to wild-type S. aureus. These findings indicate that linezolid hampers S. aureus biofilm formation by directly inhibiting icaA activity, independently of its impact on bacterial growth.

耐抗生素的金黄色葡萄球菌感染可能危及生命。已知利奈唑胺会阻碍金黄色葡萄球菌生物膜的形成,但其潜在的分子机制尚不清楚。分子对接显示利奈唑胺可以与icaA结合,这一点已通过热漂移分析得到证实。利奈唑胺对icaA酶活性具有剂量依赖性抑制作用。通过分子对接鉴定的关键残基Trp267的突变显著降低了利奈唑胺的结合和对突变体icaA活性的抑制作用。然而,与icaA相比,突变体icaA-Trp267Ala仅显示出轻微的活性降低。利奈唑胺对icaB的热稳定性和活性影响最小。50S核糖体L3ΔSer145突变体金黄色葡萄球菌表现出与野生型菌株相似的生长和生物膜形成。利奈唑胺能有效抑制野生型金黄色葡萄球菌的生长和生物膜的形成。尽管利奈唑胺失去了抑制突变菌株生长的能力,但它仍然有效地阻碍了其生物膜的形成。与野生型金黄色葡萄球菌相比,利奈唑胺对50S核糖体L3ΔSer145突变金黄色葡萄菌引起的败血症诱导的肺损伤表现出较弱的衰减。这些发现表明,利奈唑胺通过直接抑制icaA活性来阻碍金黄色葡萄球菌生物膜的形成,而与它对细菌生长的影响无关。
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引用次数: 0
Barriers to HCV micro-elimination in a cohort of people living with HIV (PLWH). HIV感染者(PLWH)队列中HCV微消除的障碍。
IF 1.8 4区 医学 Q2 Medicine Pub Date : 2023-09-01
Claudia Bartalucci, Lucia Taramasso, Laura Ambra Nicolini, Laura Magnasco, Laura Labate, Antonio Vena, Sara Mora, Mauro Giacomini, Matteo Bassetti, Antonio Di Biagio

To achieve the World Health Organization goal of hepatitis C virus (HCV) eradication, barriers to treatment should be investigated and overcome. The aim of this study was to identify those barriers and describe the strategies adopted to achieve HCV micro-elimination in a cohort of coinfected people living with HIV (PLWH-HCV). Adult PLWH-HCV followed at our hospital with detectable serum HCV-RNA in 2018 were enrolled. After a three-year follow-up, barriers to HCV treatment were investigated and strategies to overcome them were described. Of 492 PLWH-HCV seen in 2018, 29 (5.9%) had detectable serum HCV-RNA. Eight out of 29 (27.6%) were excluded because they were already under treatment, while 2 others were excluded because they moved to other outpatient clinics. Among the remaining 19 study participants, the most common barriers to treatment were poor adherence to therapies and follow-up visits (n=9, 47%), recent HCV diagnosis awaiting proper staging (n=3, 16%) and treatment hesitancy (n=2, 10%). During the following three years, direct-acting antivirals (DAAs) treatment was completed in 11/19 (58%) cases, with achievement of sustained virological response in 100% of cases. For the remaining cases, 2/19 (10.5%) were lost to follow-up, 2/19 (10.5%) died before treatment initiation and 4/19 (21.0%) are still awaiting treatment. Despite 3 years of effort, HCV micro-elimination has not been achieved at our center. We observed that poor adherence and treatment hesitancy were the main barriers to treatment. Strategies addressing these issues need to be implemented.

为了实现世界卫生组织根除丙型肝炎病毒的目标,应调查并克服治疗障碍。本研究的目的是确定这些障碍,并描述在一组HIV合并感染者(PLWH-HCV)中实现HCV微消除所采取的策略。2018年在我院随访的具有可检测血清HCV-RNA的成人PLWH-HCV被纳入研究。经过三年的随访,对HCV治疗的障碍进行了调查,并描述了克服这些障碍的策略。在2018年发现的492例PLWH-HCV中,29例(5.9%)具有可检测的血清HCV-RNA。29人中有8人(27.6%)因已经在接受治疗而被排除在外,另有2人因转到其他门诊而被排除。在剩下的19名研究参与者中,最常见的治疗障碍是对治疗和随访的依从性差(n=9,47%)、最近的HCV诊断等待适当分期(n=3,16%)和治疗犹豫(n=2,10%)。在接下来的三年里,11/19(58%)的病例完成了直接作用抗病毒药物(DAAs)治疗,100%的病例获得了持续的病毒学应答。其余病例中,2/19例(10.5%)失访,2/19人(10.5%,)在治疗开始前死亡,4/19人(21.0%)仍在等待治疗。尽管经过3年的努力,我们中心仍未实现丙型肝炎病毒的微量消除。我们观察到,依从性差和治疗犹豫是治疗的主要障碍。需要实施解决这些问题的战略。
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引用次数: 0
Determination of hepatitis C virus viremia and genotype distribution in Turkish citizens and immigrants from 2018 to 2022. 2018年至2022年土耳其公民和移民丙型肝炎病毒血症和基因型分布的测定。
IF 1.8 4区 医学 Q2 Medicine Pub Date : 2023-09-01
Murat Yaman, Salih Hazar, Ayfer Bakir

Hepatitis C virus (HCV) infection is an important public health problem with potential risk for Turkey. In order to contribute to the epidemiological data, we aimed to investigate the changes in seroprevalence, viremia rates, and genotypes in the last five years in HCV patients in the southern region of Turkey, which has received heavy migration in recent years, according to demographic criteria. In our study, we analyzed the results retrospectively with demographic data. Conducted at a single center, the study involved 259,875 anti-HCV antibody tests administered between January 2018 and July 2022. The study revealed a prevalence of 0.5% for HCV antibody positivity and a viremia prevalence of 0.1%. Among Turkish nationals, the most common genotypes were GT1 (65.1%), while foreign nationals, mainly of Syrian and Ukrainian origin, showed GT4 (52.3%) as the predominant genotype (p<0.001 for both). Although GT2 (7.4% vs. 4.5%) and GT3 (23.3% vs. 13.6%) were relatively higher in Turkish nationals compared to foreign nationals, the difference was not statistically significant (p=0.750 and p=0.154, respectively). This highlights the importance of continuous monitoring and public health efforts to address the potential impact of these demographic shifts on HCV epidemiology in the region.

丙型肝炎病毒(HCV)感染是一个重要的公共卫生问题,对土耳其有潜在风险。为了提供流行病学数据,我们旨在根据人口统计标准,调查土耳其南部地区HCV患者在过去五年中的血清流行率、病毒血症率和基因型的变化,该地区近年来经历了大量移民。在我们的研究中,我们使用人口统计数据对结果进行了回顾性分析。该研究在一个中心进行,涉及2018年1月至2022年7月期间进行的259875次抗HCV抗体测试。研究显示,丙型肝炎病毒抗体阳性率为0.5%,病毒血症率为0.1%。在土耳其国民中,最常见的基因型是GT1(65.1%),而主要来自叙利亚和乌克兰的外国国民显示GT4(52.3%)是主要基因型(p
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引用次数: 0
Optimizing Antiretroviral Therapy with Bictegravir/Emtricitabine/Tenofovir Alafenamide in virologically suppressed PLWH. Bitegravir/恩曲他滨/替诺福韦-阿拉芬酰胺在病毒抑制的PLWH中优化抗逆转录病毒治疗。
IF 1.8 4区 医学 Q2 Medicine Pub Date : 2023-09-01
Massimo Andreoni

The pillar of treatment success, defined as viral suppression and immune restoration, should be integrated into a modern vision of therapeutic success with pharmacological attributes of ART, such as potency, forgiveness, and genetic barrier of single drugs and regimens, as well as their longterm tolerability and safety. Moreover, the longterm success of lifelong treatment cannot be separated from the opinions and preferences of PLWH. Regimen Optimization in the setting of HIV suppression may reduce pill burden, and/or dosing frequency, enhance tolerability and/or decrease toxicity, prevent or mitigate DDIs, eliminate food/fluid requirements, relieve pill fatigue, decrease stigma or concerns associated with taking oral med, allow pregnancy, reduce costs (DHHS 2023). Regimen Optimization should be tailored by a person-centered perspective, based on the individual therapeutic history, past toxicities and comorbidities. The treatment strategy should be based on the perceived tolerability and quality of life, considering the preferences of people on treatment along with the virological and pharmacological factors. The health care system should facilitate universal and rapid access to personalized, robust, and effective therapies. The BIC/FTC/TAF association ensures all these characteristics and therefore represents a valid strategy for optimizing treatment in PLWH virologically suppressed.

治疗成功的支柱,被定义为病毒抑制和免疫恢复,应该结合到具有抗逆转录病毒疗法药理学属性的治疗成功的现代愿景中,如单一药物和方案的效力、宽恕和遗传屏障,以及它们的长期耐受性和安全性。此外,终身治疗的长期成功离不开PLWH的意见和偏好。HIV抑制环境中的方案优化可以减少药丸负担和/或给药频率,提高耐受性和/或降低毒性,预防或减轻DDI,消除食物/液体需求,缓解药丸疲劳,减少与口服药物相关的耻辱感或担忧,允许怀孕,降低成本(DHHS 2023)。方案优化应根据个人治疗史、既往毒性和合并症,从以人为本的角度进行调整。治疗策略应基于感知的耐受性和生活质量,考虑人们对治疗的偏好以及病毒学和药理学因素。医疗保健系统应促进普及和快速获得个性化、稳健和有效的治疗方法。BIC/FTC/TAF关联确保了所有这些特征,因此代表了优化病毒抑制的PLWH治疗的有效策略。
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引用次数: 0
Molecular epidemiology typing of blaOXA-48 and blaNDM-1 producing Klebsiella pneumoniae causing nosocomial infection. 引起医院感染的blaOXA-48和blaNDM-1产生的肺炎克雷伯菌的分子流行病学分型。
IF 1.8 4区 医学 Q2 Medicine Pub Date : 2023-09-01
Pegah Shakib, Rashid Ramazanzadeh

In this study the antibiotic susceptibility pattern and bla genes were characterized in Klebsiella pneumoniae clinical isolates that fingerprinted by rep-PCR and PFGE methods at Kurdistan Province, Iran. A total of 70 K. pneumoniae were isolated from clinical samples to detect the antimicrobial susceptibility, carbapenemase and MBL-producing isolates. The PCR assay was used to identify the bla genes. Isolates were typed by PFGE and Rep-PCR methods. The highest and lowest rates of resistance were observed in cefotaxime (67.1%) and imipenem (8.6%), respectively. The rate of blaNDM-1 and blaOXA-48 genes were 1 (1.4%) and 14 (20%) isolates, respectively. All were classified in 27 clusters by rep-PCR and 39 PFGE types. The low frequency of carbapenemase and MBL genes in this study are epidemiologically important.

在本研究中,通过rep-PCR和PFGE方法对伊朗库尔德斯坦省肺炎克雷伯菌临床分离株的抗生素敏感性模式和bla基因进行了表征。从临床样品中分离到70株肺炎克雷伯菌,检测其耐药性、碳青霉烯酶和MBL产生菌。采用聚合酶链式反应(PCR)方法对bla基因进行鉴定。通过PFGE和Rep-PCR方法对分离物进行分型。头孢噻肟(67.1%)和亚胺培南(8.6%)的耐药率最高,最低。blaNDM-1和blaOXA-48基因的检出率分别为1(1.4%)和14(20%)。通过rep-PCR将其分为27个聚类和39个PFGE类型。本研究中碳青霉烯酶和MBL基因的低频率在流行病学上具有重要意义。
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引用次数: 0
Seroprevalence of herpes simplex virus type 1 and type 2 - data from a hospital-based study in Varna, northeastern Bulgaria, 2019-2021. 2019-2021年保加利亚东北部瓦尔纳一项医院研究的单纯疱疹病毒1型和2型的血清流行率数据。
IF 1.8 4区 医学 Q2 Medicine Pub Date : 2023-09-01
Gabriela Tsankova, Tatina Todorova, Neli Ermenlieva, Gergana Nedelcheva, Zhivka Stoykova, Tsvetelina Kostadinova

The purpose of the current study was to describe the prevalence of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in northeastern Bulgaria. From January 2019 to December 2021, we tested 1493 samples for anti-HSV-1 IgG and 817 samples for anti-HSV-2 IgG antibodies in the Virology Laboratory, "St. Marina" University Hospital, Varna, Bulgaria. HSV-1 was considerably more widespread, with an overall seroprevalence of 73.3% (95% CI: 71.0-75.5%), than HSV-2 infection, which showed a seropositive rate of 10.0% (95% CI: 8.1-12.4%). Age was the most significant risk factor for both infections, while gender had no role in herpes simplex seropositivity.

本研究的目的是描述保加利亚东北部单纯疱疹病毒1型(HSV-1)和2型(HSV-2)的流行情况。从2019年1月到2021年12月,我们在保加利亚瓦尔纳“圣玛丽娜”大学医院病毒学实验室检测了1493份抗HSV-1 IgG样本和817份抗HSV-2 IgG抗体样本。HSV-1比HSV-2感染更为广泛,总血清阳性率为73.3%(95%可信区间:71.0-75.5%),HSV-2感染显示出10.0%的血清阳性率(95%置信区间:8.1-12.4%)。年龄是两种感染的最重要风险因素,而性别在单纯疱疹血清阳性中没有作用。
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引用次数: 0
Antimicrobial activity of Lactobacillus pentosus against the Bacillus cereus and Klebsiella pneumoniae strains. 戊糖乳杆菌对蜡样芽孢杆菌和肺炎克雷伯菌的抑菌活性研究。
IF 1.8 4区 医学 Q2 Medicine Pub Date : 2023-05-01
Samreen Akhtar, Syed Kashif Nawaz

Food safety is the primary concern of the food industry. The aim of the current research is to study the antimicrobial effects of cell-free supernatant of Lactobacillus pentosus against Bacillus cereus and Klebsiella pneumoniae. B. cereus and K. pneumoniae were isolated from infant formula milk product and meat sample, respectively. Their identification was performed through morphological characterization and biochemical testing. Molecular identification of K. pneumoniae was based on 16s ribotyping. A previously isolated and reported strain of L. pentosus was used for the isolation of CFS (Cellfree supernatants). Antimicrobial activity was studied through agar well diffusion assay. Inhibitory activity was recorded by measuring the zone of inhibition. CFS activity was evaluated for temperature and pH. The antimicrobial activity of CFS of L. pentosus produced at different temperatures and pH was investigated against B. cereus and K. pneumoniae. A clear zone of inhibition was observed against B. cereus while no ZOI was formed against K. pneumoniae. K. pneumoniae was found resistant to the CFS. Crude bacteriocin exhibited heat stability for a temperature of 121°C for 30 minutes and pH range of 3-7. The current study concluded that bacteriocin produced from L. pentosus can be used for the control of B. cereus. Its heat and pH stability allows its potential therapeutic use in the food industry as a food preservative and to control food poisoning cases due to B. cereus. K. pneumoniaeis was found resistant to the isolated bacteriocin, and therefore L. pentosus cannot be used for control against K. pneumoniae.

食品安全是食品工业最关心的问题。本研究的目的是研究戊酸乳杆菌无细胞上清液对蜡样芽孢杆菌和肺炎克雷伯菌的抑菌作用。从婴幼儿配方奶粉和肉类样品中分别分离到蜡样芽孢杆菌和肺炎克雷伯菌。通过形态表征和生化检测对其进行鉴定。肺炎克雷伯菌分子鉴定基于16s核糖分型。使用先前分离和报道的L. pentosus菌株分离CFS(无细胞上清液)。通过琼脂孔扩散试验研究其抑菌活性。通过测定抑制区记录抑制活性。研究了不同温度和pH条件下生产的戊糖乳杆菌CFS对蜡样芽孢杆菌和肺炎克雷伯菌的抑菌活性。对蜡样芽孢杆菌有明显的抑制区,而对肺炎克雷伯菌没有形成ZOI。肺炎克雷伯菌被发现对CFS有耐药性。粗细菌素在121℃温度下热稳定性为30分钟,pH值范围为3-7。本研究表明,戊酸乳杆菌产生的细菌素可用于控制蜡样芽孢杆菌。它的热稳定性和pH稳定性使其在食品工业中作为食品防腐剂和控制蜡样芽孢杆菌引起的食物中毒的潜在治疗用途。发现肺炎克雷伯菌对分离的细菌素具有耐药性,因此戊托菌不能用于控制肺炎克雷伯菌。
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引用次数: 0
In Silico Evaluation of SARS-CoV-2 K417N, L452R, and E484K Detection Assays Against Omicron Variants. SARS-CoV-2 K417N、L452R和E484K检测组克隆变异的计算机评价
IF 1.8 4区 医学 Q2 Medicine Pub Date : 2023-05-01
Murat Sayan, Ayse Arikan, Murat Isbilen

The study's objective was to assess whether the performance of the DIAGNOVITAL SARS-CoV-2 Mutation Detection Assays is affected by Omicron mutations. In silico evaluation of 67,717 Variant of Concern, Variant of Interest sequences and 6,612 sequences of the Omicron variants involving BA1., BA2., BA3 sub-lineages downloaded from the GISAID database by 17 December 2021, were performed. The sequences were aligned according to the reference genome MN908947.3 using MAFFT multiple sequence alignment software version 7. Our findings showed that among 6,612 Omicron, 41 Spike gene mutations with a frequency of ≥70% were identified. Some of the Omicron mutations (R408S, N440K, G446S, Q493S, Q498R) could affect the diagnostic performance of K417N, L452R, and E484K assays against the Omicron sub-lineages. However, L452R and K417N mutation tests allow differentiation of the Delta and Omicron variants mutation profile. The COVID-19 pandemic lasted longer than expected, and the rapid modification of diagnostic kits seems necessary to combat the pandemic.

该研究的目的是评估DIAGNOVITAL SARS-CoV-2突变检测方法的性能是否受到Omicron突变的影响。对涉及BA1的67,717条关注变异序列、兴趣变异序列和6,612条Omicron变异序列进行了计算机评价。,菲律宾媒体。到2021年12月17日,从GISAID数据库下载了BA3子谱系。根据参考基因组MN908947.3使用MAFFT多序列比对软件版本7进行比对。结果显示,在6612个Omicron中,有41个Spike基因突变,突变频率≥70%。部分Omicron突变(R408S、N440K、G446S、Q493S、Q498R)可能影响K417N、L452R和E484K检测对Omicron亚系的诊断性能。然而,L452R和K417N突变测试允许区分Delta和Omicron变体突变谱。COVID-19大流行持续的时间比预期的要长,快速修改诊断试剂盒似乎是抗击大流行的必要条件。
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引用次数: 0
No need to modify treatment within the first month after rapid start of a tailored antiretroviral therapy: the TWODAY Study. 在快速开始定制抗逆转录病毒治疗后的第一个月内无需修改治疗:TWODAY研究。
IF 1.8 4区 医学 Q2 Medicine Pub Date : 2023-05-01
Nicola Gianotti, Laura Galli, Michela Sampaolo, Riccardo Lolatto, Elisabetta Carini, Gaetana Annicchiarico, Alessandro Baglivi, Liviana Della Torre, Adriano Lazzarin, Antonella Castagna

The aim of the TWODAY Study was to investigate the frequency of early treatment change after rapid start of a tailored ART regimen (a 2-drug regimen - 2DR, when clinically feasible or a 3-drug regimen - 3DR, otherwise). TWODAY was an open-label, prospective, proof-of-concept, single center study. ART-naïve patients started their first-line regimen within a few days from the first laboratory testing with a 2DR of dolutegravir (DTG) and lamivudine (3TC) if CD4+ count >200 cells/mL, HIVRNA <500,000 copies/mL, no transmitted drug resistance to DTG or 3TC and HBsAg undetectable; otherwise, ART was started with a 3DR. The primary endpoint was the proportion of patients who needed to change ART within four week from start, for any reason. Thirty-two patients were enrolled; 19 (59.3%) were deemed eligible for a 2DR. Median time from laboratory testing to ART start was 5 days (5; 5). No regimen modification occurred within one month. In conclusion, no regimen modification was needed within the first month of treatment. Starting a 2DR within a few days after HIV diagnosis was feasible, relying upon complete results of the needed laboratory tests (including resistance testing). A 2DR can be safely proposed provided full laboratory tests are readily available.

TWODAY研究的目的是调查快速开始定制ART方案后早期治疗改变的频率(2药物方案- 2DR,当临床可行或3药物方案- 3DR,否则)。TWODAY是一项开放标签、前瞻性、概念验证、单中心研究。ART-naïve如果CD4+计数>200细胞/mL, HIVRNA,患者在第一次实验室检测后几天内开始使用2DR的多替格拉韦(DTG)和拉米夫定(3TC)的一线治疗方案
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引用次数: 0
Susceptibility of ceftolozane/tazobactam against multidrug-resistant and carbapenem-resistant Pseudomonas aeruginosa. 头孢唑烷/他唑巴坦对多重耐药和碳青霉烯耐药铜绿假单胞菌的敏感性。
IF 1.8 4区 医学 Q2 Medicine Pub Date : 2023-05-01
Ayaka Kakehi, Hideharu Hagiya, Koji Iio, Takumi Fujimori, Mami Okura, Hiroshi Minabe, Yukika Yokoyama, Fumio Otsuka, Akihito Higashikage

Ceftolozane (CTLZ) is a novel cephalosporin antibiotic that exhibits broad-spectrum activity against gram-negative pathogens, including Pseudomonas aeruginosa, especially when combined with tazobactam (TAZ). We examined the minimum inhibitory concentration (MIC) of CTLZ/TAZ for 21 multidrug-resistant P. aeruginosa (MDRP) and eight carbapenem-resistant P. aeruginosa (CRPA) strains isolated at Okayama University Hospital, Japan. Consequently, 81% (17/21) of the MDRP strains and 25% (2/8) of the CRPA strains were resistant to CTLZ/TAZ (MIC >8 μg/mL). All 18 blaIMP-positive strains showed resistance to CTLZ/TAZ, whereas the drug retained in vitro susceptibility in 54.5% (6/11 strains) of blaIMP-negative strains.

Ceftolozane (CTLZ)是一种新型头孢菌素抗生素,对包括铜绿假单胞菌在内的革兰氏阴性病原体具有广谱活性,特别是与他唑巴坦(TAZ)合用时。研究了CTLZ/TAZ对21株耐多药铜绿假单胞菌(P. aeruginosa, MDRP)和8株耐碳青霉烯型铜绿假单胞菌(P. aeruginosa, CRPA)的最低抑菌浓度(MIC)。结果显示,81%(17/21)的MDRP菌株和25%(2/8)的CRPA菌株对CTLZ/TAZ耐药(MIC >8 μg/mL)。18株blaimp阳性菌株对CTLZ/TAZ均有耐药性,而blaimp阴性菌株对CTLZ/TAZ的体外敏感性为54.5%(6/11株)。
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引用次数: 0
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New Microbiologica
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