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Global cell-free DNA methylation in patients with active tuberculosis and tuberculosis contacts with latent tuberculosis infection 活动性肺结核患者和肺结核潜伏感染者的全球无细胞 DNA 甲基化。
IF 2.1 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2024-10-18 DOI: 10.1016/j.diagmicrobio.2024.116559
Chih-Jung Chang , Jhong-Ru Huang , Yen-Han Tseng , Sheng-Wei Pan , Jia-Yih Feng , Wei-Juin Su , Yuh-Min Chen

Introduction

To investigate whether the methylation of circulating cell-free DNA (cfDNA) differentiates active tuberculosis (TB) from latent TB infection (LTBI).

Methods

Patients with pulmonary TB, contacts with LTBI, and healthy controls were enrolled (2018–2021). Plasma cfDNA was extracted, and using a 5-methylcytosine (5mC) DNA ELISA kit, the global methylation of cfDNA (5mC-cfDNA) was measured.

Results

59 TB, 63 LTBI, 39 healthy controls were included. The 5mC-cfDNA level was higher in TB (6.4 %) than LTBI (4.1 %) and healthy controls (4.9 %) (both p<0.05). Independent TB factors were 5mC-cfDNA ≥6.6 % and CRP ≥0.32 mg/dL (adjusted odds ratio (aOR) 4.594 [95 % CI:1.628–12.965], p=0.004 and 5.338 [1.659–17.176], p=0.005). Having one or both factors increased TB odds 8- and 16-fold (aOR 8.688 [3.229–23.378], p <0.001 and 16.080 [3.092–83.632], p =0.001).

Conclusion

The global cfDNA methylation level was higher in TB than contacts without TB and helped differentiate patients with TB from contacts with LTBI.
简介:目的:研究循环游离细胞 DNA(cfDNA)的甲基化是否能区分活动性结核病(TB)和潜伏性结核感染(LTBI):研究循环无细胞DNA(cfDNA)的甲基化是否能区分活动性肺结核(TB)和潜伏性肺结核感染(LTBI):入组肺结核患者、LTBI接触者和健康对照组(2018-2021年)。提取血浆cfDNA,使用5-甲基胞嘧啶(5mC)DNA ELISA试剂盒测定cfDNA的全局甲基化(5mC-cfDNA):结果:59 名肺结核患者、63 名长期慢性阻塞性肺病患者和 39 名健康对照者被纳入研究。结核病患者的 5mC-cfDNA 水平(6.4%)高于长期慢性阻塞性肺病患者(4.1%)和健康对照组(4.9%)(均为 p):肺结核患者的 cfDNA 整体甲基化水平高于无肺结核的接触者,有助于区分肺结核患者和长期慢性阻塞性肺病接触者。
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引用次数: 0
Determination of limit of detection (LOD) for loop-mediated isothermal amplification (LAMP) of human cytomegalovirus (hCMV) DNA 确定人类巨细胞病毒 (hCMV) DNA 的环介导等温扩增 (LAMP) 检测限 (LOD)。
IF 2.1 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2024-10-18 DOI: 10.1016/j.diagmicrobio.2024.116567
Erkan Mozioğlu , Martin Hussels , Susanne Engel
The importance of cytomegalovirus in clinical practice remains and samples are monitored for CMV DNA titers to predict the development of disease. LAMP assays have gained increasing interest in the diagnosis of many pathogens since they do not require thermocycling, reduce the complexity of the required instrumentation as well as providing sensitivity and rapidity. So far, very few studies on CMV detection by LAMP have been reported in the literature and therefore the performance of LAMP CMV assays needs to be further characterized. In a set-up for biometrological evaluation of the suitability of the LAMP assay for CMV diagnosis, a LAMP assay was performed on a total of 192 samples with 24 replicates of 8 different hCMV DNA concentrations. The LOD was calculated as 39.09 copy/reaction (25.33 copy/reaction to 65.84 copy/reaction) with 95 % confidence, representing a range that is suitable for qualitative detection. Furthermore, the lower limit of quantification was estimated at approximately 100 copy/reaction. The LOD and LLOQ values obtained in this first study to assess the biometrological relevance of LAMP CMV tests are consistent when compared to studies published before. However further study under different conditions is needed for the use of LAMP tests in clinical applications.
巨细胞病毒在临床实践中的重要性依然存在,人们通过监测样本中的巨细胞病毒 DNA 滴度来预测疾病的发展。LAMP 检测法无需热循环,降低了所需仪器的复杂性,灵敏度高且快速,因此在许多病原体的诊断中越来越受到关注。迄今为止,文献中关于通过 LAMP 检测 CMV 的研究报道很少,因此需要进一步确定 LAMP CMV 检测方法的性能。为了对 LAMP 检测法是否适用于 CMV 诊断进行生物计量学评估,我们对 8 种不同 hCMV DNA 浓度的 192 份样本进行了 24 次重复的 LAMP 检测。计算得出的 LOD 为 39.09 拷贝/反应(25.33 拷贝/反应至 65.84 拷贝/反应),置信度为 95%,这代表了适合定性检测的范围。此外,定量下限估计约为 100 个拷贝/反应。这项首次评估 LAMP CMV 检测生物计量学相关性的研究得出的 LOD 和 LLOQ 值与之前发表的研究结果一致。不过,在临床应用中使用 LAMP 检测还需要在不同条件下进行进一步研究。
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引用次数: 0
Attenuated neutralization, maintained specificity: Humoral response to SARS-CoV-2 booster in kidney allograft recipients 中和减弱,特异性保持:肾移植受者对 SARS-CoV-2 强化剂的体液反应。
IF 2.1 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2024-10-16 DOI: 10.1016/j.diagmicrobio.2024.116550
Martina Fialova , Eva Cecrdlova , Ivan Zahradka , Vojtech Petr , Filip Hruby , Istvan Modos , Ondrej Viklicky , Ilja Striz
Despite the lower virulence of current SARS-CoV-2 variants and high rates of vaccinated and previously infected subjects, COVID-19 remains a persistent threat in kidney transplant recipients (KTRs). This study evaluated the parameters of anti-SARS-CoV-2 antibody production in 120 KTRs. The production of neutralizing antibodies in KTRs, following booster vaccination with the mRNA vaccine BNT162b2, was significantly decreased and their decline was faster than in healthy subjects. Factors predisposing to the downregulation of anti-SARS-CoV-2 neutralizing antibodies included age, lower estimated glomerular filtration rate, and a full dose of mycophenolate mofetil. Neutralizing antibodies correlated with those targeting the SARS-CoV-2 receptor binding domain (RBD), SARS-CoV-2 Spike trimmer, total SARS-CoV-2 S1 protein, as well as with antibodies to the deadly SARS-CoV-1 virus. No cross-reactivity was found with antibodies against seasonal coronaviruses. KTRs exhibited lower postvaccination production of neutralizing antibodies against SARS-CoV-2; however, the specificity of their humoral response did not differ compared to healthy subjects.
尽管目前的 SARS-CoV-2 变体毒力较低,而且接种疫苗的受试者和以前感染过的受试者比例较高,但 COVID-19 仍是肾移植受者(KTR)的一个长期威胁。这项研究评估了 120 名 KTR 中抗 SARS-CoV-2 抗体产生的参数。KTR在接种mRNA疫苗BNT162b2后,中和抗体的产生量明显下降,且下降速度快于健康受试者。导致抗SARS-CoV-2中和抗体下调的因素包括年龄、较低的估计肾小球滤过率和全剂量的霉酚酸酯。中和抗体与针对SARS-CoV-2受体结合域(RBD)、SARS-CoV-2穗状修饰体、SARS-CoV-2 S1总蛋白以及致命的SARS-CoV-1病毒的抗体相关。与季节性冠状病毒抗体没有交叉反应。KTR 接种后产生的针对 SARS-CoV-2 的中和抗体较低;但与健康人相比,其体液反应的特异性并无差异。
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引用次数: 0
MALDI-TOF MS profiling to predict resistance or biofilm production in gram-positive ESKAPE pathogens from healthcare-associated infections 用 MALDI-TOF MS 图谱预测医疗相关感染中革兰氏阳性 ESKAPE 病原体的抗药性或生物膜生成。
IF 2.1 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2024-10-14 DOI: 10.1016/j.diagmicrobio.2024.116562
Aldo Sebastian Flores-Flores , Jose Manuel Vazquez-Guillen , Paola Bocanegra-Ibarias , Adrian Camacho-Ortiz , Reyes S. Tamez-Guerra , Cristina Rodriguez-Padilla , Samantha Flores-Treviño
Antimicrobial resistance and biofilm production in healthcare-associated infections is a health issue worldwide. This study aimed to identify potential biomarker peaks for resistance or biofilm production in ESKAPE pathogens using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility and biofilm production were assessed on selected isolates. Biomarker peaks were identified using MALDI Biotyper and ClinProTools software. Among resistant strains, 90.0 % were carbapenem-resistant Acinetobacter baumannii (CRAB), 39.0 % were methicillin-resistant Staphylococcus aureus (MRSA), 17.98 % were multidrug-resistant (MDR) Pseudomonas aeruginosa, 21.6 % were vancomycinresistant Enterococcus (VRE), and 2.55 % were carbapenem-resistant Enterobacterales (CRE). Biofilm production was 40.0 % in VRE and 45.8 % in MRSA. Although no potential biomarker peaks for biofilm production were detected, several potential biomarker peaks for drug resistance in VRE (n=5), MRSA (n=4), and MDR P. aeruginosa (n=4) were detected, suggesting avenues for the development of rapid diagnostic tools.
医疗相关感染中的抗菌药耐药性和生物膜产生是一个全球性的健康问题。本研究旨在利用基质辅助激光解吸电离飞行时间质谱法(MALDI-TOF MS)鉴定 ESKAPE 病原体耐药性或生物膜产生的潜在生物标志物峰。对部分分离菌株的抗菌药敏感性和生物膜生成情况进行了评估。使用 MALDI Biotyper 和 ClinProTools 软件识别生物标记峰。耐药菌株中,90.0%为耐碳青霉烯类鲍曼不动杆菌(CRAB),39.0%为耐甲氧西林金黄色葡萄球菌(MRSA),17.98%为耐多药铜绿假单胞菌(MDR),21.6%为耐万古霉素肠球菌(VRE),2.55%为耐碳青霉烯类肠球菌(CRE)。生物膜产生率在 VRE 中为 40.0%,在 MRSA 中为 45.8%。虽然没有检测到生物膜产生的潜在生物标志物峰值,但在 VRE(5 个)、MRSA(4 个)和 MDR 铜绿假单胞菌(4 个)中检测到了几个潜在的耐药性生物标志物峰值,这为开发快速诊断工具提供了途径。
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引用次数: 0
Ceftriaxone versus cefepime or carbapenems for definitive treatment of low-risk AmpC-Harboring Enterobacterales bloodstream infections in hospitalized adults: A retrospective cohort study 头孢曲松与头孢吡肟或碳青霉烯类药物用于住院成人低风险安普碳耐药肠杆菌血流感染的最终治疗:一项回顾性队列研究。
IF 2.1 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2024-10-13 DOI: 10.1016/j.diagmicrobio.2024.116557
Jessica L. Mulbah , Rachel M. Kenney , Robert J. Tibbetts , Anita B. Shallal , Michael P. Veve

Objective

To compare outcomes of ceftriaxone to AmpC-stable therapies in patients with bacteremia caused by low-risk AmpC harboring Enterobacterales.

Methods

IRB-approved, retrospective cohort of hospitalized patients ≥18 years old with Serratia marcescens, Morganella morganii, or Providencia spp. bacteremia from 1/1/2017-2/28/2024. Patients were compared by definitive therapy with ceftriaxone vs AmpC-stable therapy (cefepime, carbapenem). The primary endpoint was 30-day all-cause mortality; secondary endpoints were clinical failure and development of ceftriaxone resistance.

Results

163 patients were included; 33.1 % received ceftriaxone, 66.9 % AmpC-stable therapies. 30-day all-cause mortality was 9.3 % ceftriaxone vs 10.1 % AmpC stable patients (P = 0.87); ceftriaxone definitive therapy was not associated with 30-day all-cause mortality (adjOR, 0.79; 95 %CI, 0.23-2.3). There were no differences in clinical failure (9.3 % vs 21.1 %, P = 0.059) or relapsing infection (5.6 % vs 9.3 %, P = 0.55) between ceftriaxone and AmpC-stable treated patients.

Conclusions

Patients treated with definitive ceftriaxone for low-risk AmpC Enterobacterales bacteremia had similar outcomes to AmpC stable therapies.
目的比较头孢曲松和AmpC稳定疗法对低风险AmpC肠杆菌引起的菌血症患者的治疗效果:方法:经IRB批准,对2017年1月1日-2024年2月28日期间年龄≥18岁、患有马氏沙雷氏菌、摩根氏菌或普罗维登斯菌属菌血症的住院患者进行回顾性队列研究。患者采用头孢曲松与AmpC稳定疗法(头孢吡肟、碳青霉烯)进行比较。主要终点是30天全因死亡率;次要终点是临床失败和头孢曲松耐药性的产生:共纳入 163 名患者;33.1% 的患者接受了头孢曲松治疗,66.9% 的患者接受了 AmpC 稳定疗法。头孢曲松与 AmpC 稳定型患者的 30 天全因死亡率分别为 9.3% 和 10.1%(P = 0.87);头孢曲松最终疗法与 30 天全因死亡率无关(adjOR,0.79;95 %CI,0.23-2.3)。头孢曲松和AmpC稳定治疗患者的临床失败率(9.3% vs 21.1%,P = 0.059)或复发感染率(5.6% vs 9.3%,P = 0.55)没有差异:结论:接受头孢曲松治疗的低风险AmpC肠杆菌菌血症患者与接受AmpC稳定疗法的患者疗效相似。
{"title":"Ceftriaxone versus cefepime or carbapenems for definitive treatment of low-risk AmpC-Harboring Enterobacterales bloodstream infections in hospitalized adults: A retrospective cohort study","authors":"Jessica L. Mulbah ,&nbsp;Rachel M. Kenney ,&nbsp;Robert J. Tibbetts ,&nbsp;Anita B. Shallal ,&nbsp;Michael P. Veve","doi":"10.1016/j.diagmicrobio.2024.116557","DOIUrl":"10.1016/j.diagmicrobio.2024.116557","url":null,"abstract":"<div><h3>Objective</h3><div>To compare outcomes of ceftriaxone to AmpC-stable therapies in patients with bacteremia caused by low-risk AmpC harboring Enterobacterales.</div></div><div><h3>Methods</h3><div>IRB-approved, retrospective cohort of hospitalized patients ≥18 years old with <em>Serratia marcescens, Morganella morganii</em>, or <em>Providencia</em> spp. bacteremia from 1/1/2017-2/28/2024. Patients were compared by definitive therapy with ceftriaxone vs AmpC-stable therapy (cefepime, carbapenem). The primary endpoint was 30-day all-cause mortality; secondary endpoints were clinical failure and development of ceftriaxone resistance.</div></div><div><h3>Results</h3><div>163 patients were included; 33.1 % received ceftriaxone, 66.9 % AmpC-stable therapies. 30-day all-cause mortality was 9.3 % ceftriaxone vs 10.1 % AmpC stable patients (<em>P</em> = 0.87); ceftriaxone definitive therapy was not associated with 30-day all-cause mortality (adjOR, 0.79; 95 %CI, 0.23-2.3). There were no differences in clinical failure (9.3 % vs 21.1 %, <em>P</em> = 0.059) or relapsing infection (5.6 % vs 9.3 %, <em>P</em> = 0.55) between ceftriaxone and AmpC-stable treated patients.</div></div><div><h3>Conclusions</h3><div>Patients treated with definitive ceftriaxone for low-risk AmpC Enterobacterales bacteremia had similar outcomes to AmpC stable therapies.</div></div>","PeriodicalId":11329,"journal":{"name":"Diagnostic microbiology and infectious disease","volume":"111 1","pages":"Article 116557"},"PeriodicalIF":2.1,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluation of nonpolar lipid extract antigen-based enzyme-linked immunosorbent assay for the serodiagnosis of tuberculosis 评估基于非极性脂质提取物抗原的酶联免疫吸附试验在结核病血清诊断中的应用。
IF 2.1 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2024-10-13 DOI: 10.1016/j.diagmicrobio.2024.116560
Luana E. Araújo , Jéssica Petrilli , Carlos Oliveira , Thainá Horta , Paulo Estevão , Fabiana Rabe Carvalho , Claudete A. Araújo Cardoso , Thiago Marconi Cardoso , Luanna de Ângelis , Lilian Montenegro , Fred Luciano Neves Santos , Sérgio Arruda , Adriano Queiroz
This study assessed the diagnostic potential of nonpolar lipid extracts in enzyme-linked immunosorbent assays (ELISAs) for tuberculosis (TB) serodiagnosis. Nonpolar lipid extracts were harvested from Mycobacterium tuberculosis (Mtb) knockout in mce1 operon (∆mce1) and its parental wild type (WT) strains. IgM and IgG anti-nonpolar lipid serum levels were measured in TB patients (n=45), healthy individuals with positive (n=22) and negative (n=44) interferon-gamma release assay (IGRA) results, and symptomatic respiratory (SR) patients with negative TB tests (n=9). IgG anti-WT lipid distinguished TB patients from IGRA-positive individuals with 60% sensitivity and 77.3% specificity. Conversely, IgG anti-∆mce lipid levels didn't vary significantly across groups. Interestingly, most SR patients exhibited significantly higher IgM and IgG anti-WT lipid titers than the IGRA-positive and -nega groups. While the overall diagnostic potential of Mtb nonpolar lipids was limited, the impaired immunogenecity of Δmce1 lipid extract suggests that some missing lipid classes in this extract can potentially induce antibody production in TB patients.
本研究评估了非极性脂质提取物在用于结核病(TB)血清诊断的酶联免疫吸附试验(ELISA)中的诊断潜力。非极性脂质提取物取自 mce1 操作子敲除的结核分枝杆菌(Mtb)(Δmce1)及其亲本野生型(WT)菌株。对结核病患者(45 人)、干扰素-γ 释放测定(IGRA)结果为阳性(22 人)和阴性(44 人)的健康人以及结核病检测结果为阴性的有症状呼吸道(SR)患者(9 人)的血清 IgM 和 IgG 抗非极性脂质水平进行了测定。IgG 抗 WT 脂质可将肺结核患者与 IGRA 阳性者区分开来,灵敏度为 60%,特异性为 77.3%。相反,IgG 抗Δmce 脂质水平在各组间没有显著差异。有趣的是,大多数 SR 患者的 IgM 和 IgG 抗 WT 脂质滴度明显高于 IGRA 阳性组和-nega 组。虽然Mtb非极性脂质的总体诊断潜力有限,但Δmce1脂质提取物的免疫原性受损表明,该提取物中某些缺失的脂质类别有可能诱导肺结核患者产生抗体。
{"title":"Evaluation of nonpolar lipid extract antigen-based enzyme-linked immunosorbent assay for the serodiagnosis of tuberculosis","authors":"Luana E. Araújo ,&nbsp;Jéssica Petrilli ,&nbsp;Carlos Oliveira ,&nbsp;Thainá Horta ,&nbsp;Paulo Estevão ,&nbsp;Fabiana Rabe Carvalho ,&nbsp;Claudete A. Araújo Cardoso ,&nbsp;Thiago Marconi Cardoso ,&nbsp;Luanna de Ângelis ,&nbsp;Lilian Montenegro ,&nbsp;Fred Luciano Neves Santos ,&nbsp;Sérgio Arruda ,&nbsp;Adriano Queiroz","doi":"10.1016/j.diagmicrobio.2024.116560","DOIUrl":"10.1016/j.diagmicrobio.2024.116560","url":null,"abstract":"<div><div>This study assessed the diagnostic potential of nonpolar lipid extracts in enzyme-linked immunosorbent assays (ELISAs) for tuberculosis (TB) serodiagnosis. Nonpolar lipid extracts were harvested from <em>Mycobacterium tuberculosis</em> (Mtb) knockout in <em>mce1</em> operon (∆mce1) and its parental wild type (WT) strains. IgM and IgG anti-nonpolar lipid serum levels were measured in TB patients (n=45), healthy individuals with positive (n=22) and negative (n=44) interferon-gamma release assay (IGRA) results, and symptomatic respiratory (SR) patients with negative TB tests (n=9). IgG anti-WT lipid distinguished TB patients from IGRA-positive individuals with 60% sensitivity and 77.3% specificity. Conversely, IgG anti-∆mce lipid levels didn't vary significantly across groups. Interestingly, most SR patients exhibited significantly higher IgM and IgG anti-WT lipid titers than the IGRA-positive and -nega groups. While the overall diagnostic potential of Mtb nonpolar lipids was limited, the impaired immunogenecity of Δmce1 lipid extract suggests that some missing lipid classes in this extract can potentially induce antibody production in TB patients.</div></div>","PeriodicalId":11329,"journal":{"name":"Diagnostic microbiology and infectious disease","volume":"111 1","pages":"Article 116560"},"PeriodicalIF":2.1,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Colistin, doxycycline and Labetalol-meropenem combination are the most active against XDR-Carbapenem-resistant Acinetobacter baumannii: Role of a novel transferrable plasmid conferring carbapenem resistance 可乐定、强力霉素和拉贝洛尔-美罗培南组合对耐XDR-碳青霉烯类鲍曼不动杆菌最有效:赋予碳青霉烯耐药性的新型可转移质粒的作用
IF 2.1 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2024-10-12 DOI: 10.1016/j.diagmicrobio.2024.116558
Heba Mohammed Refat M. Selim , Fatma Alzahraa M. Gomaa , Mohammad Y. Alshahrani , Noha A. Kamel , Khaled M. Aboshanab , Khaled M. Elsayed
This study aimed to evaluate the antimicrobial susceptibility and combination of a beta-blocker, labetalol (LAB) and meropenem (MEM) on Carbapenem-resistant (CR) A. baumannii clinical isolates. A total of 43 CR- A. baumannii were isolated of which 37 (86.6 %) and 28 (65 %) exhibited MDR and XDR phenotypes, respectively. Colistin and doxycycline still retain their activities in 93.1 % and 72.1 % of the isolates, respectively. Combining MEM with LAB at 0.25 mg /mL, decreased MIC values in 91.4 % (32/35) however, at 0.5 mg /mL, it decreased MIC value and restored susceptibility to MEM in 100 % and 91.4 % of the tested isolates, respectively. A novel transferable plasmid pAcbGIM3 harboring aph-3′, blaoxa-58, blaGIM3 and blaCTX-M3 and eight mobile genetic elements were successfully isolated from a pan-drug resistant (PDR) isolate. In conclusion, LAB-MEM is a promising combination and should be clinically examined. This is the first report of a transmissible plasmid harboring blaGIM3 gene in Egypt.
本研究旨在评估β-受体阻滞剂拉贝洛尔(LAB)和美罗培南(MEM)对耐碳青霉烯类(CR)鲍曼氏菌临床分离株的抗菌药敏感性和联合用药情况。共分离出 43 株对卡巴培南耐药的鲍曼尼氏菌,其中 37 株(86.6%)和 28 株(65%)分别表现出 MDR 和 XDR 表型。可乐定和强力霉素仍分别在 93.1% 和 72.1% 的分离物中保持活性。在 0.25 毫克/毫升的浓度下,将 MEM 与 LAB 结合使用可降低 91.4% (32/35)的 MIC 值,但在 0.5 毫克/毫升的浓度下,MEM 可降低 100% 的 MIC 值,并使 91.4% 的受试分离物恢复对 MEM 的敏感性。从一个具有泛耐药性(PDR)的分离株中成功分离出了一个新型可转移质粒 pAcbGIM3,该质粒含有 aph-3′、blaoxa-58、blaGIM3 和 blaCTX-M3 以及八个移动遗传元件。总之,LAB-MEM 是一种很有前景的组合,应在临床上加以研究。这是埃及首次报道携带 blaGIM3 基因的可传播质粒。
{"title":"Colistin, doxycycline and Labetalol-meropenem combination are the most active against XDR-Carbapenem-resistant Acinetobacter baumannii: Role of a novel transferrable plasmid conferring carbapenem resistance","authors":"Heba Mohammed Refat M. Selim ,&nbsp;Fatma Alzahraa M. Gomaa ,&nbsp;Mohammad Y. Alshahrani ,&nbsp;Noha A. Kamel ,&nbsp;Khaled M. Aboshanab ,&nbsp;Khaled M. Elsayed","doi":"10.1016/j.diagmicrobio.2024.116558","DOIUrl":"10.1016/j.diagmicrobio.2024.116558","url":null,"abstract":"<div><div>This study aimed to evaluate the antimicrobial susceptibility and combination of a beta-blocker, labetalol (LAB) and meropenem (MEM) on Carbapenem-resistant (CR) <em>A. baumannii</em> clinical isolates. A total of 43 CR- <em>A. baumannii</em> were isolated of which 37 (86.6 %) and 28 (65 %) exhibited MDR and XDR phenotypes, respectively. Colistin and doxycycline still retain their activities in 93.1 % and 72.1 % of the isolates, respectively. Combining MEM with LAB at 0.25 mg /mL, decreased MIC values in 91.4 % (32/35) however, at 0.5 mg /mL, it decreased MIC value and restored susceptibility to MEM in 100 % and 91.4 % of the tested isolates, respectively. A novel transferable plasmid pAcbGIM3 harboring <em>aph</em>-3′, <em>bla</em><sub>oxa-58,</sub> <em>bla</em><sub>GIM3</sub> and <em>bla</em><sub>CTX-M3</sub> and eight mobile genetic elements were successfully isolated from a pan-drug resistant (PDR) isolate. In conclusion, LAB-MEM is a promising combination and should be clinically examined. This is the first report of a transmissible plasmid harboring <em>bla</em><sub>GIM3</sub> gene in Egypt.</div></div>","PeriodicalId":11329,"journal":{"name":"Diagnostic microbiology and infectious disease","volume":"110 4","pages":"Article 116558"},"PeriodicalIF":2.1,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In vitro activity of zidebactam/cefepime (WCK 5222), a β-lactam enhancer/ β-lactam combination against carbapenem- and colistin-resistant Klebsiella pneumoniae isolates zidebactam/cefepime (WCK 5222)是一种β-内酰胺增强剂/β-内酰胺复方制剂,对耐碳青霉烯类和耐秋水仙碱肺炎克雷伯菌分离物的体外活性。
IF 2.1 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2024-10-12 DOI: 10.1016/j.diagmicrobio.2024.116561
Yamuna Devi Bakthavatchalam , Chaitra Shankar , Christo Jeyaraj , Ayyanraj Neeravi , Purva Mathur , Vasant Nagvekar , Sangeetha Nithiyanandam , Kamini Walia , Balaji Veeraraghavan

Objectives

In vitro activity of β-lactam enhancer/β-lactam combination zidebactam/cefepime was evaluated against carbapenem- and colistin-resistant Klebsiella pneumoniae isolates.

Methods

Non duplicate K. pneumoniae (n=185), resistant to colistin as well as non-susceptible to carbapenems were collected (2018-2019) at two large tertiary care hospitals in India. Colistin resistance-conferring genes mcr1 and mcr3 were screened among 123 of 185 randomly-selected isolates. These isolates were also subjected to multi-locus sequence typing (MLST). Additionally, alterations in mgrB were screened in 109 of these 123 isolates. All the study isolates were screened for presence of carbapenemases genes. MICs of zidebactam/cefepime, colistin, carbapenems, ceftazidime/avibactam, imipenem/relebactam, amikacin and piperacillin/tazobactam were determined by reference CLSI broth dilution method.

Results

Among the isolates, 65.4% (121/185) carried blaOXA-48-like gene and 27.6% isolates (51/185) carried dual carbapenemase genes; blaOXA-48-like and blaNDM. Of the remainder, 8 isolates carried blaNDM and 5 isolates lacked carbapenemases gene despite being carbapenem-resistant. None of the isolates showed presence of mcr1 and mcr3. Out of 109 isolates analysed for mgrB, 36 showed mutational changes. The MLST profile revealed at least 14 unique sequence types with ST231 being the dominant clone. All the isolates showed colistin MICs >2 mg/L and were non-susceptible to carbapenems. Zidebactam/cefepime demonstrated potent activity with MIC50 and MIC90 of 1 and 2 mg/L, respectively. MIC90s of amikacin, ceftazidime/avibactam and imipenem/relebactam were >32 mg/L.

Conclusion

Zidebactam/cefepime combination was highly active against multi-clonal, carbapenem-non-susceptible and colistin-resistant K. pneumoniae isolates producing OXA-48-like (Ambler class D) or/and NDM (Ambler class B) carbapenemases, thus potentially offering a valuable treatment options for infections caused by such pan-drug resistant resistotypes. Though, zidebactam is not an inhibitor of class B and D β-lactamases, potent activity of zidebactam/cefepime combination is attributable to β-lactam enhancer mechanism.
目的评估β-内酰胺增强剂/β-内酰胺组合齐德巴坦/头孢吡肟对碳青霉烯类和耐可乐定肺炎克雷伯菌分离株的体外活性:在印度两家大型三级医院收集了对可乐定耐药和对碳青霉烯类不耐药的非重复肺炎克雷伯菌(n=185)(2018-2019年)。在随机挑选的 185 个分离株中,对 123 个分离株的耐药基因 mcr1 和 mcr3 进行了筛查。还对这些分离株进行了多焦点序列分型(MLST)。此外,还对这 123 个分离株中的 109 个进行了 mgrB 变异筛查。对所有研究分离物进行了碳青霉烯酶基因筛选。参照 CLSI 肉汤稀释法测定了齐德巴坦/头孢吡肟、考来霉素、碳青霉烯类、头孢他啶/阿维菌素、亚胺培南/雷巴坦、阿米卡星和哌拉西林/他唑巴坦的 MIC 值:在分离菌株中,65.4%(121/185)携带 blaOXA-48-like 基因,27.6%(51/185)携带双重碳青霉烯酶基因;blaOXA-48-like 和 blaNDM。其余分离物中,8 个携带 blaNDM 基因,5 个缺乏碳青霉烯酶基因,但对碳青霉烯类耐药。没有一个分离物显示存在 mcr1 和 mcr3。在分析了 109 个 mgrB 分离物中,有 36 个出现了突变。MLST 图谱显示至少有 14 种独特的序列类型,其中 ST231 是主要的克隆。所有分离菌株的可乐定 MIC 均大于 2 毫克/升,对碳青霉烯类不敏感。齐德巴坦/头孢吡肟具有很强的活性,其 MIC50 和 MIC90 分别为 1 毫克/升和 2 毫克/升。阿米卡星、头孢他啶/阿维菌素和亚胺培南/雷巴坦的 MIC90 均大于 32 毫克/升:结论:齐德巴坦/头孢吡肟复方制剂对产生 OXA-48 样(安布勒 D 类)或/和 NDM(安布勒 B 类)碳青霉烯酶的多克隆、碳青霉烯类不耐药和耐可乐定的肺炎克氏菌分离株具有很高的活性,因此有可能为此类泛耐药菌株引起的感染提供有价值的治疗方案。虽然齐德巴坦不是 B 类和 D 类β-内酰胺酶的抑制剂,但齐德巴坦/头孢吡肟复方制剂的强效活性可归因于β-内酰胺增强机制。
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引用次数: 0
Omadacycline for the treatment of severe Legionella pneumophila pneumonia complicated with multiple organ dysfunction: a case report 奥马他环素治疗严重嗜肺军团菌肺炎并发多器官功能障碍:病例报告
IF 2.1 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2024-10-10 DOI: 10.1016/j.diagmicrobio.2024.116553
Jinfeng Lv , Chun Liu , Lan Fan , Ping Luo , Shao Liu , Cuifang Wu
Omadacycline is a novel tetracycline antibiotic that has a strong in vitro antibacterial activity against atypical pathogen such as Legionella. It is approved for the treatment of adults with community-acquired bacterial pneumonia, including Legionella pneumonia. However, clinical data on the use of omadacycline in Legionella pneumonia is limited. In the present paper, we report a case of severe pneumonia induced by Legionella pneumophila (L.pneumophila) presenting with septic shock and multiple organ dysfunction including lung, liver and kidney. With omadacycline treaetment, inflammation indices of the patient markedly decreased, and the patient significantly improved with multiple organ dysfunction and was discharged from home. Due to its strong antibacterial activity against L.pneumophila, good safety profile and no dosage adjustment in patients with severe hepatic or renal impairment, omadacycline can be considered as an optimal treatment strategies for severe infections by such special pathogen. Whereas, more case reports are needed to support this conclusion.
奥马他环素是一种新型四环素类抗生素,对军团菌等非典型病原体具有很强的体外抗菌活性。它被批准用于治疗成人社区获得性细菌性肺炎,包括军团菌肺炎。然而,有关奥马他环素用于军团菌肺炎的临床数据十分有限。本文报告了一例由嗜肺军团菌(L.pneumophila)诱发的重症肺炎病例,患者出现脓毒性休克和肺、肝、肾等多器官功能障碍。经奥美拉唑治疗后,患者的炎症指标明显降低,多器官功能障碍明显改善,康复出院。由于奥美拉唑对嗜肺菌有很强的抗菌活性,安全性好,且对严重肝肾功能损害的患者无需调整剂量,因此可将奥美拉唑作为此类特殊病原体严重感染的最佳治疗策略。不过,还需要更多的病例报告来支持这一结论。
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引用次数: 0
A Case of Pulmonary Tularemia Mimicking Lung Cancer 一个模仿肺癌的肺土拉菌病病例
IF 2.1 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2024-10-09 DOI: 10.1016/j.diagmicrobio.2024.116554
Yasemin Çakır Kıymaz , Mahmut Özbey
Tularemia is a zoonotic infectious disease caused by Francisella tularensis. The main reservoir for F. tularensis is lagomorphs, rodents, arthropods, and the hydrotelluric environment. It also can be transmitted by infected animals or by drinking contaminated water. Pulmonary tularemia is a rare form of tularemia mostly transmitted by inhalation. In this report, we present a 51-year-old male patient who was admitted to the hospital with fever, cough, sputum, and chest pain. Biopsy of the lesion compatible with mass on chest radiography revealed granulomatous inflammation. The diagnosis of pulmonary tularemia was made based on a history of rodent contact and tularemia microagglutination test (MAT): 1/1280.
土拉菌病是一种由土拉菌弗朗西斯菌引起的人畜共患传染病。土拉菌病的主要传染源是袋鼠、啮齿动物、节肢动物和水生环境。它也可通过受感染的动物或饮用受污染的水传播。肺土拉菌病是一种罕见的土拉菌病,主要通过吸入传播。在本报告中,我们介绍了一名因发热、咳嗽、咳痰和胸痛入院的 51 岁男性患者。对胸片上与肿块相匹配的病灶进行活检后发现了肉芽肿性炎症。根据啮齿动物接触史和土拉菌微凝集试验(MAT),诊断为肺土拉菌病:1/1280.
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Diagnostic microbiology and infectious disease
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