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Microbial metagenomic shifts in children with acute lymphoblastic leukaemia during induction therapy and predictive biomarkers for infection. 急性淋巴细胞白血病患儿在诱导治疗期间的微生物元基因组变化以及感染的预测性生物标志物。
IF 5.7 2区 医学 Q1 MICROBIOLOGY Pub Date : 2024-06-15 DOI: 10.1186/s12941-024-00717-z
Huidi Wang, Yajie Zhang, Qianyi Zhou, Lihua Yu, Jingxiang Fu, Danna Lin, Lulu Huang, Xiaorong Lai, Li Wu, Jingxin Zhang, Juan Zi, Xu Liao, Siying Huang, Yugu Xie, Yan He, Lihua Yang

Background: Emerging evidence has indicated a link between the gut microbiota and acute lymphoblastic leukaemia (ALL). However, the acute changes in gut microbiota during chemotherapy and the predictive value of baseline gut microbiota in infectious complication remain largely unknown.

Methods: Faecal samples (n = 126) from children with ALL (n = 49) undergoing induction chemotherapy were collected at three timepoints, i.e., initiation of chemotherapy (baseline, T0), 7 days (T1) and 33 days (T2) after initiation of chemotherapy. Gut microbiome profile was performed via metagenomic shotgun sequencing. The bioBakery3 pipeline (Kneaddata, Metaphlan 3 and HUMAnN) was performed to assign taxonomy and functional annotations. Gut microbiome at T0 were used to predict infection during chemotherapy.

Results: The microbial diversities and composition changed significantly during chemotherapy, with Escherichia coli, Klebsiella pneumoniae and Bifidobacterium longum being the most prominent species. The microbial metabolic pathways were also significantly altered during chemotherapy, including the pathway of pyruvate fermentation to acetate and lactate, and assimilatory sulfate reduction pathway. The receiver operating characteristic (ROC) models based on Bifidobacterium longum at T0 could predict infectious complications during the first month of chemotherapy with the area under the curve (AUC) of 0.720.

Conclusions: Our study provides new insights into the acute changes in microbial and functional characteristics in children with ALL during chemotherapy. The baseline gut microbiota could be potential biomarkers for infections during chemotherapy.

Trial registration: The study was approved by the Ethics Committee of Zhujiang Hospital, Southern Medical University (2021-KY-171-01) and registered on http://www.chictr.org.cn (ChiCTR2200065406, Registration Date: November 4, 2022).

背景:新的证据表明,肠道微生物群与急性淋巴细胞白血病(ALL)之间存在联系。然而,化疗期间肠道微生物群的急性变化以及基线肠道微生物群对感染性并发症的预测价值在很大程度上仍然未知:方法:在化疗开始(基线,T0)、化疗开始后 7 天(T1)和化疗开始后 33 天(T2)三个时间点收集正在接受诱导化疗的 ALL 患儿(49 人)的粪便样本(126 份)。通过元基因组霰弹枪测序对肠道微生物组进行了分析。采用 bioBakery3 管道(Kneaddata、Metaphlan 3 和 HUMAnN)进行分类和功能注释。利用T0时的肠道微生物组预测化疗期间的感染情况:结果:化疗期间微生物的多样性和组成发生了显著变化,大肠埃希氏菌、肺炎克雷伯氏菌和长双歧杆菌是最主要的物种。化疗期间微生物的代谢途径也发生了明显变化,包括丙酮酸发酵至醋酸盐和乳酸盐的途径以及硫酸盐同化还原途径。基于T0时长双歧杆菌的接收者操作特征(ROC)模型可以预测化疗第一个月的感染并发症,其曲线下面积(AUC)为0.720:我们的研究为了解 ALL 患儿化疗期间微生物和功能特征的急性变化提供了新的视角。基线肠道微生物群可能是化疗期间感染的潜在生物标志物:本研究经南方医科大学珠江医院伦理委员会批准(2021-KY-171-01),并在http://www.chictr.org.cn(ChiCTR2200065406,注册日期:2022年11月4日)。
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引用次数: 0
Nanopore sequencing for smear-negative pulmonary tuberculosis-a multicentre prospective study in China. 针对涂片阴性肺结核的纳米孔测序--一项在中国开展的多中心前瞻性研究。
IF 4.6 2区 医学 Q1 MICROBIOLOGY Pub Date : 2024-06-14 DOI: 10.1186/s12941-024-00714-2
Xiaojing Yan, Guoli Yang, Yunfei Wang, Yuqing Wang, Jie Cheng, Peisong Xu, Xiaoli Qiu, Lei Su, Lina Liu, Ruixue Geng, Yingxia You, Hui Liu, Naihui Chu, Li Ma, Wenjuan Nie

Purpose: In this prospective study, the diagnosis accuracy of nanopore sequencing-based Mycobacterium tuberculosis (MTB) detection was determined through examining bronchoalveolar lavage fluid (BALF) samples from pulmonary tuberculosis (PTB) -suspected patients. Compared the diagnostic performance of nanopore sequencing, mycobacterial growth indicator tube (MGIT) culture and Xpert MTB/rifampin resistance (MTB/RIF) assays.

Methods: Specimens collected from suspected PTB cases across China from September 2021 to April 2022 were tested then assay diagnostic accuracy rates were compared.

Results: Among the 111 suspected PTB cases that were ultimately diagnosed as PTB, the diagnostic rate of nanopore sequencing was statistically significant different from other assays (P < 0.05). Fleiss' kappa values of 0.219 and 0.303 indicated fair consistency levels between MTB detection results obtained using nanopore sequencing versus other assays, respectively. Respective PTB diagnostic sensitivity rates of MGIT culture, Xpert MTB/RIF and nanopore sequencing of 36.11%, 40.28% and 83.33% indicated superior sensitivity of nanopore sequencing. Analysis of area under the curve (AUC), Youden's index and accuracy values and the negative predictive value (NPV) indicated superior MTB detection performance for nanopore sequencing (with Xpert MTB/RIF ranking second), while the PTB diagnostic accuracy rate of nanopore sequencing exceeded corresponding rates of the other methods.

Conclusions: In comparison with MGIT culture and Xpert MTB/RIF assays, BALF's nanopore sequencing provided superior MTB detection sensitivity and thus is suitable for testing of sputum-scarce suspected PTB cases. However, negative results obtained using these assays should be confirmed based on additional evidence before ruling out a PTB diagnosis.

目的:在这项前瞻性研究中,通过检测肺结核(PTB)疑似患者的支气管肺泡灌洗液(BALF)样本,确定了基于纳米孔测序的结核分枝杆菌(MTB)检测的诊断准确性。比较了纳米孔测序、分枝杆菌生长指示管(MGIT)培养和 Xpert MTB/利福平耐药性(MTB/RIF)测定的诊断性能:方法:对2021年9月至2022年4月期间收集的全国疑似PTB病例标本进行检测,然后比较检测诊断准确率:结果:在最终确诊为PTB的111例疑似PTB病例中,纳米孔测序的诊断率与其他检测方法相比差异有统计学意义(P 结论:纳米孔测序的诊断率与其他检测方法相比差异有统计学意义(P):与 MGIT 培养和 Xpert MTB/RIF 检测法相比,BALF 的纳米孔测序法具有更高的 MTB 检测灵敏度,因此适用于检测痰液稀少的疑似 PTB 病例。不过,在排除 PTB 诊断之前,应根据其他证据确认使用这些检测方法得出的阴性结果。
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引用次数: 0
In search of the best method to detect carriage of carbapenem-resistant Pseudomonas aeruginosa in humans: a systematic review. 寻找检测人体耐碳青霉烯类假单胞菌携带的最佳方法:系统综述。
IF 5.7 2区 医学 Q1 MICROBIOLOGY Pub Date : 2024-06-10 DOI: 10.1186/s12941-024-00707-1
Selvi N Shahab, Anneloes van Veen, Andrea C Büchler, Yulia R Saharman, Anis Karuniawati, Margreet C Vos, Anne F Voor In 't Holt, Juliëtte A Severin

Background: Detection of carbapenem-resistant Pseudomonas aeruginosa (CR-PA) in humans is important to prevent transmission. However, the most optimal culture method to detect CR-PA is unknown. This systematic review aims to determine which culture method is most sensitive and which culture methods are used to detect CR-PA in humans. Second, to establish the most feasible culture method taking into account the turnaround time (TAT), and third, to provide an overview of the sampling sites used to detect carriage.

Methods: We systematically searched the electronic databases Embase, Medline Ovid, Cochrane, Scopus, CINAHL, and Web of Science until January 27, 2023. All diagnostic accuracy studies comparing two or more culture methods to detect CR-PA and recent outbreak or surveillance reports on CR-PA carriage or infection in humans, which describe culture methods and their results, were eligible for inclusion. We used QUADAS-2 guideline for diagnostic accuracy studies and the STROBE or ORION guideline for outbreak-surveillance studies to assess the risk of bias.

Results: Six diagnostic accuracy studies were included. An enrichment broth was found to increase the detection of CR-PA. Using an enrichment broth extended the TAT by 18-24 h, yet selective media could reduce the TAT by 24 h compared to routine media. In total, 124 outbreak-surveillance studies were included, of which 17 studies with surveillance samples and 116 studies with clinical samples. In outbreak-surveillance studies with surveillance samples, perianal, rectal swabs or stools were the most common sampling site/specimen (13/17, 76%). A large variety was observed in whether and which kind of enrichment broth and selective media were used.

Conclusions: We found a benefit of using an enrichment step prior to inoculation of the material onto selective media for the detection of CR-PA. More research is needed to determine the most sensitive sampling site and culture method.

Trail registration: This study was registered in the PROSPERO International prospective register of systematic reviews (registration number: CRD42020207390, http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42020207390 ).

背景:检测人体内耐碳青霉烯类的铜绿假单胞菌(CR-PA)对于预防传播非常重要。然而,检测 CR-PA 的最佳培养方法尚不清楚。本系统综述旨在确定哪种培养方法最灵敏,以及哪些培养方法可用于检测人体内的 CR-PA。其次,考虑到周转时间(TAT),确定最可行的培养方法;第三,概述用于检测携带的采样点:截至 2023 年 1 月 27 日,我们系统地检索了 Embase、Medline Ovid、Cochrane、Scopus、CINAHL 和 Web of Science 等电子数据库。所有比较两种或两种以上检测CR-PA的培养方法的诊断准确性研究,以及近期有关CR-PA携带或感染人类的疫情或监测报告,只要描述了培养方法及其结果,均符合纳入条件。我们采用QUADAS-2指南来评估诊断准确性研究,采用STROBE或ORION指南来评估疫情监测研究的偏倚风险:结果:共纳入了六项诊断准确性研究。结果:共纳入了六项诊断准确性研究。使用增菌肉汤可将TAT延长18-24小时,但与常规培养基相比,选择性培养基可将TAT缩短24小时。共纳入了 124 项疫情监测研究,其中 17 项研究使用了监测样本,116 项研究使用了临床样本。在使用监测样本的疫情监测研究中,肛周、直肠拭子或粪便是最常见的采样部位/样本(13/17,76%)。在是否使用增菌肉汤和选择性培养基以及使用哪种增菌肉汤和选择性培养基方面,我们观察到了很大的差异:我们发现,在将材料接种到选择性培养基上检测 CR-PA 之前使用富集步骤有好处。需要开展更多研究,以确定最敏感的采样部位和培养方法:本研究已在 PROSPERO 国际前瞻性系统综述注册中心注册(注册号:CRD42020207390):CRD42020207390, http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42020207390 )。
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引用次数: 0
Chronic endometritis and the endometrial microbiota: implications for reproductive success in patients with recurrent implantation failure. 慢性子宫内膜炎与子宫内膜微生物群:对反复植入失败患者生殖成功的影响。
IF 5.7 2区 医学 Q1 MICROBIOLOGY Pub Date : 2024-05-30 DOI: 10.1186/s12941-024-00710-6
Hong Zhang, Heng Zou, Chanyu Zhang, Shen Zhang

Background: Chronic endometritis (CE) is associated with poor reproductive outcomes, yet the role of endometrial microbiota in patients with recurrent implantation failure (RIF) and CE remains unclear. This study aims to characterize endometrial microbiota in RIF patients with CE and assess its implications for reproductive outcomes.

Methods: In this prospective study, we enrolled RIF patients both with and without CE. Endometrial and cervical samples were collected for 16 S rRNA gene sequencing. Microbiota composition was compared between groups using diversity indices, phylum, and genus-level analysis. Canonical correlation analysis (CCA) and Spearman's correlation coefficients were used to assess relationships between CE, reproductive outcomes, and microbiota. Predictive functional profiling was performed to evaluate metabolic pathways associated with CE.

Results: Endometrial microbiota in CE patients exhibited greater diversity and evenness compared to non-CE patients. Principal coordinates analysis (PCoA) revealed distinct clustering between CE and non-CE groups. Linear discriminant analysis (LDA) identified Proteobacteria, Aminicenantales, and Chloroflexaceae as characteristic of CE, while Lactobacillus, Acinetobacter, Herbaspirillum, Ralstonia, Shewanela, and Micrococcaceae were associated with non-CE. CCA demonstrated associations between CE, adverse reproductive outcomes, and specific bacterial taxa. Microbial metabolic pathways significantly differed between CE and non-CE groups, with enrichment in pathways related to cofactors, vitamins, secondary metabolites, and the immune system in CE patients.

Conclusion: RIF patients with CE exhibit distinct endometrial microbiota compositions associated with adverse reproductive outcomes. The increased microbial diversity and altered metabolic pathways in CE suggest a potential correlation with reproductive outcomes, although further studies are necessary to elucidate the causal relationship between microbiota alterations and fertility. Modulating the endometrial microbiome may represent a novel therapeutic strategy to improve IVF outcomes in patients with CE.

背景:慢性子宫内膜炎(CE)与不良生殖结局相关,但子宫内膜微生物群在复发性种植失败(RIF)和CE患者中的作用仍不清楚。本研究旨在描述RIF合并CE患者子宫内膜微生物群的特征,并评估其对生殖结局的影响:在这项前瞻性研究中,我们招募了有和没有 CE 的 RIF 患者。收集子宫内膜和宫颈样本,进行 16 S rRNA 基因测序。使用多样性指数、门和属级分析比较不同组间的微生物群组成。采用典型相关分析(CCA)和斯皮尔曼相关系数评估 CE、生殖结果和微生物群之间的关系。预测性功能分析用于评估与 CE 相关的代谢途径:结果:与非 CE 患者相比,CE 患者的子宫内膜微生物群表现出更高的多样性和均匀性。主坐标分析(PCoA)显示 CE 组和非 CE 组之间存在明显的聚类。线性判别分析(LDA)发现,变形杆菌、氨基链球菌和绿藻科(Chloroflexaceae)是 CE 的特征,而乳酸杆菌、醋酸杆菌、草吸菌、Ralstonia、Shewanela 和微球菌科(Micrococcaceae)则与非 CE 相关。CCA显示了CE、不良生殖结果和特定细菌类群之间的关联。CE组和非CE组之间的微生物代谢途径存在显著差异,CE患者与辅因子、维生素、次级代谢产物和免疫系统有关的途径更为丰富:结论:患有 CE 的 RIF 患者表现出与不良生殖结局相关的独特子宫内膜微生物群组成。子宫内膜异位症患者体内微生物多样性的增加和代谢途径的改变表明,这可能与生殖结果有关,但要阐明微生物群改变与生育能力之间的因果关系,还需要进一步的研究。调节子宫内膜微生物群可能是改善 CE 患者试管受精结果的一种新型治疗策略。
{"title":"Chronic endometritis and the endometrial microbiota: implications for reproductive success in patients with recurrent implantation failure.","authors":"Hong Zhang, Heng Zou, Chanyu Zhang, Shen Zhang","doi":"10.1186/s12941-024-00710-6","DOIUrl":"10.1186/s12941-024-00710-6","url":null,"abstract":"<p><strong>Background: </strong>Chronic endometritis (CE) is associated with poor reproductive outcomes, yet the role of endometrial microbiota in patients with recurrent implantation failure (RIF) and CE remains unclear. This study aims to characterize endometrial microbiota in RIF patients with CE and assess its implications for reproductive outcomes.</p><p><strong>Methods: </strong>In this prospective study, we enrolled RIF patients both with and without CE. Endometrial and cervical samples were collected for 16 S rRNA gene sequencing. Microbiota composition was compared between groups using diversity indices, phylum, and genus-level analysis. Canonical correlation analysis (CCA) and Spearman's correlation coefficients were used to assess relationships between CE, reproductive outcomes, and microbiota. Predictive functional profiling was performed to evaluate metabolic pathways associated with CE.</p><p><strong>Results: </strong>Endometrial microbiota in CE patients exhibited greater diversity and evenness compared to non-CE patients. Principal coordinates analysis (PCoA) revealed distinct clustering between CE and non-CE groups. Linear discriminant analysis (LDA) identified Proteobacteria, Aminicenantales, and Chloroflexaceae as characteristic of CE, while Lactobacillus, Acinetobacter, Herbaspirillum, Ralstonia, Shewanela, and Micrococcaceae were associated with non-CE. CCA demonstrated associations between CE, adverse reproductive outcomes, and specific bacterial taxa. Microbial metabolic pathways significantly differed between CE and non-CE groups, with enrichment in pathways related to cofactors, vitamins, secondary metabolites, and the immune system in CE patients.</p><p><strong>Conclusion: </strong>RIF patients with CE exhibit distinct endometrial microbiota compositions associated with adverse reproductive outcomes. The increased microbial diversity and altered metabolic pathways in CE suggest a potential correlation with reproductive outcomes, although further studies are necessary to elucidate the causal relationship between microbiota alterations and fertility. Modulating the endometrial microbiome may represent a novel therapeutic strategy to improve IVF outcomes in patients with CE.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"23 1","pages":"49"},"PeriodicalIF":5.7,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11140900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Potential antivirulence activity of sub-inhibitory concentrations of ciprofloxacin against Proteus mirabilis isolates: an in-vitro and in-vivo study. 亚抑制浓度环丙沙星对奇异变形杆菌分离株的潜在抗病毒活性:体外和体内研究。
IF 5.7 2区 医学 Q1 MICROBIOLOGY Pub Date : 2024-05-27 DOI: 10.1186/s12941-024-00704-4
Mohamed A Elhosseini, Tarek E El-Banna, Fatma I Sonbol, Maisra M El-Bouseary

Background: Proteus mirabilis is a significant nosocomial pathogen that is frequently associated with a wide range of infections, necessitating heightened attention to mitigate potential health risks. Hence, this study was performed to investigate the impact of sub-minimum inhibitory concentrations (MICs) of ciprofloxacin (CIP) on Proteus mirabilis clinical isolates.

Methods: The sub-MICs of CIP were selected using the growth curve approach. The untreated and treated isolates with sub-MICs of CIP were assessed for their biofilm development, motilities on agar, and other virulence factors. The cell morphology of untreated and treated isolates with sub-MIC of CIP was explored using electron microscope. Moreover, the expression levels of the virulence genes in isolates were measured using quantitative real-time PCR.

Results: Data revealed that sub-MICs of CIP significantly (p < 0.05), in a concentration-dependent manner, inhibited biofilm formation and other virulence factors in the selected isolates. Electron microscope analysis showed cell enlargement and various abnormalities in the cell wall and membrane integrity.

Conclusion: Sub-MICs of CIP exhibited inhibition of virulence and alterations in morphological integrity against P. mirabilis isolates.

背景:奇异变形杆菌是一种重要的院内病原体,经常与多种感染有关,因此有必要加强关注以降低潜在的健康风险。因此,本研究调查了环丙沙星(CIP)次最低抑菌浓度(MIC)对奇异变形杆菌临床分离株的影响:方法:采用生长曲线法选择 CIP 的亚最低抑菌浓度。方法:采用生长曲线法筛选出 CIP 亚 MICs,并对未处理和处理过的 CIP 亚 MICs 分离物进行生物膜发育、琼脂上的运动和其他毒力因子评估。使用电子显微镜观察了未经处理和经处理的亚微克 CIP 分离物的细胞形态。此外,还利用实时定量 PCR 技术测定了分离物中毒力基因的表达水平:结果:数据显示,CIP 的亚 MIC 显著(P结果:数据显示,CIP 亚微粒对 mirabilis 分离物的毒力和形态完整性的改变具有抑制作用。
{"title":"Potential antivirulence activity of sub-inhibitory concentrations of ciprofloxacin against Proteus mirabilis isolates: an in-vitro and in-vivo study.","authors":"Mohamed A Elhosseini, Tarek E El-Banna, Fatma I Sonbol, Maisra M El-Bouseary","doi":"10.1186/s12941-024-00704-4","DOIUrl":"10.1186/s12941-024-00704-4","url":null,"abstract":"<p><strong>Background: </strong>Proteus mirabilis is a significant nosocomial pathogen that is frequently associated with a wide range of infections, necessitating heightened attention to mitigate potential health risks. Hence, this study was performed to investigate the impact of sub-minimum inhibitory concentrations (MICs) of ciprofloxacin (CIP) on Proteus mirabilis clinical isolates.</p><p><strong>Methods: </strong>The sub-MICs of CIP were selected using the growth curve approach. The untreated and treated isolates with sub-MICs of CIP were assessed for their biofilm development, motilities on agar, and other virulence factors. The cell morphology of untreated and treated isolates with sub-MIC of CIP was explored using electron microscope. Moreover, the expression levels of the virulence genes in isolates were measured using quantitative real-time PCR.</p><p><strong>Results: </strong>Data revealed that sub-MICs of CIP significantly (p < 0.05), in a concentration-dependent manner, inhibited biofilm formation and other virulence factors in the selected isolates. Electron microscope analysis showed cell enlargement and various abnormalities in the cell wall and membrane integrity.</p><p><strong>Conclusion: </strong>Sub-MICs of CIP exhibited inhibition of virulence and alterations in morphological integrity against P. mirabilis isolates.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"23 1","pages":"48"},"PeriodicalIF":5.7,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11131287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of testing methods assessing the in vitro efficacy of the combination of aztreonam with avibactam on multidrug-resistant Gram-negative bacilli 评估阿曲霉素与阿维菌素复方制剂对耐多药革兰氏阴性杆菌体外疗效的测试方法比较
IF 5.7 2区 医学 Q1 MICROBIOLOGY Pub Date : 2024-05-25 DOI: 10.1186/s12941-024-00708-0
Corentin Deckers, Florian Bélik, Olivier Denis, Pierre Bogaerts, Isabel Montesinos, Catherine Berhin, Warda Bouchahrouf, Martin Hoebeke, Stephanie Evrard, Nicolas Gilliard, Merve Okur, Te-Din Huang
Aztreonam-avibactam (ATM-AVI) combination shows promising effectiveness on most carbapenemase-producing Gram-negatives, yet standardized antibiotic susceptibility testing (AST) methods for evaluating the combination in clinical laboratories is lacking. We aimed to evaluate different ATM-AVI AST approaches. 96 characterized carbapenem-resistant clinical isolates belonging to 9 Enterobacterales (EB; n = 80) and P. aeruginosa (PA; n = 16) species, including 90 carbapenemase producers and 72 strains resistant to both CAZ-AVI and ATM, were tested. Paper disk elution (DE; Bio-Rad) and E-test gradient strips stacking (SS; bioMérieux) were performed for the ATM + CAZ-AVI combination. MIC Test Strip (MTS; Liofilchem) was evaluated for ATM-AVI MIC determination. Results were interpreted applying ATM clinical breakpoints of the EUCAST guidelines and compared to the broth microdilution method (Sensititre, Thermofisher). According to broth microdilution method, 93% of EB and 69% of PA were tested susceptible to ATM-AVI. The synergistic effect of ATM-AVI was of 95% for EB, but of only 17% for PA. The MTS method yielded higher categorical and essential agreement (CA/EA) rates for both EB (89%/91%) and PA (94%/94%) compared to SS, where the rates were 87%/83% for EB and 81%/81% for PA. MTS and SS yielded 2 and 3 major discrepancies, respectively, while 3 very major discrepancies each were observed for both methods. Concerning the DE method, CA reached 91% for EB and 81% for PA, but high number of very major discrepancies were observed for EB (n = 6; 8%) and for PA (n = 3; 19%). The ATM-AVI association displayed excellent in vitro activity against highly resistant clinical Enterobacterales strains. MTS method offers accurate ATM-AVI AST results, while the SS method might serve as better alternative then DE method in assessing the efficacy of ATM + CAZ-AVI combination. However, further investigation is needed to confirm the methods' ability to detect ATM-AVI resistance.
阿奇霉素-阿维菌素(ATM-AVI)组合对大多数产碳青霉烯酶的革兰氏阴性菌有很好的疗效,但临床实验室缺乏评估该组合的标准化抗生素药敏试验(AST)方法。我们旨在评估不同的 ATM-AVI AST 方法。我们对 96 株特征化的耐碳青霉烯类临床分离株进行了测试,这些分离株属于 9 种肠杆菌属(EB;n = 80)和铜绿假单胞菌属(PA;n = 16),其中包括 90 株碳青霉烯酶产生株和 72 株对 CAZ-AVI 和 ATM 均耐药的菌株。对 ATM + CAZ-AVI 组合进行了纸盘洗脱(DE;Bio-Rad)和 E 测试梯度条堆叠(SS;生物梅里埃)。MIC测试带(MTS;Liofilchem)用于测定ATM-AVI的MIC。检测结果根据欧盟 CAST 指南的 ATM 临床断点进行解释,并与肉汤微量稀释法(Sensititre,Thermofisher)进行比较。根据肉汤微稀释法,93% 的 EB 和 69% 的 PA 对 ATM-AVI 易感。ATM-AVI 对 EB 的增效作用为 95%,但对 PA 的增效作用仅为 17%。与 SS 相比,MTS 方法对 EB(89%/91%)和 PA(94%/94%)的分类和基本一致率(CA/EA)更高,EB 为 87%/83%,PA 为 81%/81%。MTS 和 SS 分别产生了 2 次和 3 次重大差异,而两种方法各出现了 3 次非常重大的差异。在 DE 方法中,EB 的 CA 达到 91%,PA 达到 81%,但 EB(n = 6;8%)和 PA(n = 3;19%)出现了大量的极不一致。ATM-AVI 联合物对高耐药性临床肠杆菌菌株具有出色的体外活性。MTS 法可提供准确的 ATM-AVI AST 结果,而 SS 法在评估 ATM + CAZ-AVI 组合的疗效方面可能比 DE 法更好。不过,要确认这些方法检测 ATM-AVI 耐药性的能力,还需要进一步的研究。
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引用次数: 0
Emergence of extensive drug resistance and high prevalence of multidrug resistance among clinical Proteus mirabilis isolates in Egypt. 埃及奇异变形杆菌临床分离株中出现广泛耐药性和多重耐药性的高流行率。
IF 5.7 2区 医学 Q1 MICROBIOLOGY Pub Date : 2024-05-24 DOI: 10.1186/s12941-024-00705-3
Maggi ElTaweel, Heba Shehta Said, Rasha Barwa

Background: Proteus mirabilis is an opportunistic pathogen that has been held responsible for numerous nosocomial and community-acquired infections which are difficult to be controlled because of its diverse antimicrobial resistance mechanisms.

Methods: Antimicrobial susceptibility patterns of P. mirabilis isolates collected from different clinical sources in Mansoura University Hospitals, Egypt was determined. Moreover, the underlying resistance mechanisms and genetic relatedness between isolates were investigated.

Results: Antimicrobial susceptibility testing indicated elevated levels of resistance to different classes of antimicrobials among the tested P. mirabilis clinical isolates (n = 66). ERIC-PCR showed great diversity among the tested isolates. Six isolates (9.1%) were XDR while all the remaining isolates were MDR. ESBLs and AmpCs were detected in 57.6% and 21.2% of the isolates, respectively, where blaTEM, blaSHV, blaCTX-M, blaCIT-M and blaAmpC were detected. Carbapenemases and MBLs were detected in 10.6 and 9.1% of the isolates, respectively, where blaOXA-48 and blaNDM-1 genes were detected. Quinolone resistant isolates (75.8%) harbored acc(6')-Ib-cr, qnrD, qnrA, and qnrS genes. Resistance to aminoglycosides, trimethoprim-sulfamethoxazole and chloramphenicol exceeded 80%. Fosfomycin was the most active drug against the tested isolates as only 22.7% were resistant. Class I or II integrons were detected in 86.4% of the isolates. Among class I integron positive isolates, four different gene cassette arrays (dfrA17- aadA5, aadB-aadA2, aadA2-lnuF, and dfrA14-arr-3-blaOXA-10-aadA15) and two gene cassettes (dfrA7 and aadA1) were detected. While class II integron positive isolates carried four different gene cassette arrays (dfrA1-sat1-aadA1, estXVr-sat2-aadA1, lnuF- dfrA1-aadA1, and dfrA1-sat2).

Conclusion: P. Mirabilis ability to acquire resistance determinants via integrons may be held responsible for the elevated rates of antimicrobial resistance and emergence of XDR or even PDR strains limiting the available therapeutic options for management of infections caused by those strains.

背景:mirabilis 变形杆菌是一种机会性病原体,是众多医院内感染和社区获得性感染的罪魁祸首,由于其具有多种抗菌药耐药机制而难以控制:方法:对从埃及曼苏拉大学医院不同临床来源采集的P. mirabilis分离株的抗菌药敏感性模式进行了测定。此外,还调查了分离株之间的潜在耐药机制和遗传相关性:结果:抗菌药敏感性测试表明,受测的奇异变形杆菌临床分离株(n = 66)对不同类别抗菌药的耐药性水平较高。ERIC-PCR显示受测分离株之间存在很大的多样性。有 6 个分离株(9.1%)具有 XDR,而其余所有分离株都具有 MDR。分别有 57.6% 和 21.2% 的分离物检测到 ESBLs 和 AmpCs,其中检测到 blaTEM、blaSHV、blaCTX-M、blaCIT-M 和 blaAmpC。在检测到 blaOXA-48 和 blaNDM-1 基因的分离物中,分别有 10.6% 和 9.1% 检测到碳青霉烯酶和 MBL。喹诺酮耐药分离物(75.8%)携带 acc(6')-Ib-cr、qnrD、qnrA 和 qnrS 基因。对氨基糖苷类、三甲双氨-磺胺甲噁唑和氯霉素的耐药性超过 80%。磷霉素是对测试分离株最有效的药物,只有 22.7% 的分离株对其产生耐药性。在 86.4% 的分离株中检测到了 I 类或 II 类整合子。在 I 类整合素阳性的分离物中,检测到了四个不同的基因盒阵列(dfrA17- aadA5、aadB-aadA2、aadA2-lnuF 和 dfrA14-arr-3-blaOXA-10-aadA15)和两个基因盒(dfrA7 和 aadA1)。而 II 类整合素阳性分离物携带有 4 个不同的基因盒阵列(dfrA1-sat1-aadA1、estXVr-sat2-aadA1、lnuF- dfrA1-aadA1 和 dfrA1-sat2):结论:P. Mirabilis通过整合子获得抗药性决定因子的能力可能是抗菌药耐药率升高和XDR甚至PDR菌株出现的原因,这限制了治疗由这些菌株引起的感染的可用疗法。
{"title":"Emergence of extensive drug resistance and high prevalence of multidrug resistance among clinical Proteus mirabilis isolates in Egypt.","authors":"Maggi ElTaweel, Heba Shehta Said, Rasha Barwa","doi":"10.1186/s12941-024-00705-3","DOIUrl":"10.1186/s12941-024-00705-3","url":null,"abstract":"<p><strong>Background: </strong>Proteus mirabilis is an opportunistic pathogen that has been held responsible for numerous nosocomial and community-acquired infections which are difficult to be controlled because of its diverse antimicrobial resistance mechanisms.</p><p><strong>Methods: </strong>Antimicrobial susceptibility patterns of P. mirabilis isolates collected from different clinical sources in Mansoura University Hospitals, Egypt was determined. Moreover, the underlying resistance mechanisms and genetic relatedness between isolates were investigated.</p><p><strong>Results: </strong>Antimicrobial susceptibility testing indicated elevated levels of resistance to different classes of antimicrobials among the tested P. mirabilis clinical isolates (n = 66). ERIC-PCR showed great diversity among the tested isolates. Six isolates (9.1%) were XDR while all the remaining isolates were MDR. ESBLs and AmpCs were detected in 57.6% and 21.2% of the isolates, respectively, where bla<sub>TEM</sub>, bla<sub>SHV</sub>, bla<sub>CTX-M</sub>, bla<sub>CIT-M</sub> and bla<sub>AmpC</sub> were detected. Carbapenemases and MBLs were detected in 10.6 and 9.1% of the isolates, respectively, where bla<sub>OXA-48</sub> and bla<sub>NDM-1</sub> genes were detected. Quinolone resistant isolates (75.8%) harbored acc(6')-Ib-cr, qnrD, qnrA, and qnrS genes. Resistance to aminoglycosides, trimethoprim-sulfamethoxazole and chloramphenicol exceeded 80%. Fosfomycin was the most active drug against the tested isolates as only 22.7% were resistant. Class I or II integrons were detected in 86.4% of the isolates. Among class I integron positive isolates, four different gene cassette arrays (dfrA17- aadA5, aadB-aadA2, aadA2-lnuF, and dfrA14-arr-3-bla<sub>OXA-10</sub>-aadA15) and two gene cassettes (dfrA7 and aadA1) were detected. While class II integron positive isolates carried four different gene cassette arrays (dfrA1-sat1-aadA1, estXVr-sat2-aadA1, lnuF- dfrA1-aadA1, and dfrA1-sat2).</p><p><strong>Conclusion: </strong>P. Mirabilis ability to acquire resistance determinants via integrons may be held responsible for the elevated rates of antimicrobial resistance and emergence of XDR or even PDR strains limiting the available therapeutic options for management of infections caused by those strains.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"23 1","pages":"46"},"PeriodicalIF":5.7,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141092462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phenotypic and genotypic analysis of antimicrobial resistance and population structure of gastroenteritis-related Aeromonas isolates. 对与肠胃炎相关的气单胞菌分离物的抗菌药耐药性和种群结构进行表型和基因型分析。
IF 5.7 2区 医学 Q1 MICROBIOLOGY Pub Date : 2024-05-23 DOI: 10.1186/s12941-024-00706-2
Dana Sagas, Yizhak Hershko, Katia Levitskyi, Merav Strauss, Matan Slutzkin, Bibiana Chazan, Amos Adler

Background: The population structure and the correlation between antimicrobial resistance (AMR) phenotypes and genotypes in Aeromonas species isolated from patients with gastroenteritis are not well understood. The aims of the study were to: (1) investigate the antimicrobial susceptibility profiles of Aeromonas species isolated from patients with gastroenteritis; (2) explore the relationship between AMR genes and resistance phenotypes; and (3) describe the population structure of these isolates and provide evidence of transmission events among them.

Methods: This microbiological survey was performed at the Microbiology Laboratory of the Emek Medical Center in Afula, Israel. Cultivation of Aeromonas was attempted from stool samples that tested positive by PCR. Antimicrobial susceptibility testing (AST) was performed using the Sensititre GN3F microdilution panel. Whole genome sequencing (WGS) was done using the Illumina NextSeq500/550 system. Phylogenetic studies involved multi-locus sequence typing (MLST) and core genome (cg) MLST. Resistance mechanisms were identified using the Comprehensive Antibiotic Resistance Database and compared with the AST results.

Results: The study included 67 patient-unique isolates. The species that were identified included A. caviae (n = 58), A. dhakensis (n = 3), A. media (n = 2), A. veronii (n = 2) and A. hydrophila (n = 2). Isolates were almost uniformly susceptible to amikacin, gentamicin, aztreonam, cefepime, ceftazidime, ciprofloxacin and meropenem. All isolates with the exception of 1-2 isolates were resistant to ampicillin, cefazolin and ampicillin-sulbactam which was compatible with the presence of the blaOXA genes. Variable resistance rates were observed to cefuroxime, cefoxitin, ceftriaxone, piperacillin-tazobactam that were not correlated with the presence of other β-lactamase genes. Resistance to tetracycline and trimethoprim-sulfamethoxazole correlated with the presence of tetA and sul1, respectively. The population structure of A. caviae was highly diverse with the minority of the isolates (16/57) clustering into six defined sequence types. A cgMLST-based distance of four genes was found in one pair of isolates, suggesting common source transmission.

Conclusions: A. caviae is the dominant species related to gastroenteritis and is characterized by a diverse population structure, with almost no evidence for common-source transmission. Resistance rates to most antimicrobial agents were low and partially matched with the presence of resistance genes.

背景:从肠胃炎患者体内分离出的气单胞菌的种群结构以及抗菌药耐药性(AMR)表型和基因型之间的相关性尚不十分清楚。本研究旨在(1) 调查从肠胃炎患者体内分离出的气单胞菌的抗菌药敏感性特征;(2) 探讨 AMR 基因与耐药性表型之间的关系;(3) 描述这些分离株的种群结构,并提供它们之间传播事件的证据:这项微生物学调查在以色列阿富拉埃梅克医疗中心的微生物实验室进行。尝试从 PCR 检测呈阳性的粪便样本中培养气单胞菌。使用 Sensititre GN3F 微稀释板进行了抗菌药物敏感性测试 (AST)。使用 Illumina NextSeq500/550 系统进行了全基因组测序(WGS)。系统发育研究包括多焦点序列分型(MLST)和核心基因组(cg)MLST。利用抗生素耐药性综合数据库确定耐药性机制,并与 AST 结果进行比较:研究包括 67 个病人独特的分离株。结果:该研究包括 67 个患者特有的分离菌株,鉴定出的菌种包括:A. caviae(n = 58)、A. dhakensis(n = 3)、A. media(n = 2)、A. veronii(n = 2)和 A. hydrophila(n = 2)。分离菌株对阿米卡星、庆大霉素、阿曲南、头孢吡肟、头孢他啶、环丙沙星和美罗培南几乎一致敏感。除 1-2 个分离株外,所有分离株都对氨苄西林、头孢唑啉和氨苄西林-舒巴坦有耐药性,这与 blaOXA 基因的存在相符。对头孢呋辛、头孢西丁、头孢曲松、哌拉西林-他唑巴坦的耐药率不尽相同,这与存在其他β-内酰胺酶基因无关。对四环素和三甲氧苄嘧啶-磺胺甲噁唑的抗药性分别与 tetA 和 sul1 的存在有关。鱼腥酵母菌的种群结构具有高度多样性,少数分离株(16/57)可分为六种明确的序列类型。在一对分离物中发现了基于 cgMLST 的四个基因的距离,这表明它们具有共同的传播源:结论:腔肠动物是与肠胃炎相关的主要物种,其种群结构多样,几乎没有共同来源传播的证据。对大多数抗菌药物的耐药率较低,且部分与耐药基因的存在相匹配。
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引用次数: 0
Dual-function antimicrobial-antibiofilm peptide hybrid to tackle biofilm-forming Staphylococcus epidermidis. 双功能抗菌-抗生物膜肽混合物,用于对付形成生物膜的表皮葡萄球菌。
IF 5.7 2区 医学 Q1 MICROBIOLOGY Pub Date : 2024-05-16 DOI: 10.1186/s12941-024-00701-7
Mathira Wongchai, Saharut Wongkaewkhiaw, Sakawrat Kanthawong, Sittiruk Roytrakul, Ratchaneewan Aunpad
<p><strong>Background: </strong>Due to their resistance and difficulty in treatment, biofilm-associated infections are problematic among hospitalized patients globally and account for 60% of all bacterial infections in humans. Antibiofilm peptides have recently emerged as an alternative treatment since they can be effectively designed and exert a different mode of biofilm inhibition and eradication.</p><p><strong>Methods: </strong>A novel antibiofilm peptide, BiF, was designed from the conserved sequence of 18 α-helical antibiofilm peptides by template-assisted technique and its activity was improved by hybridization with a lipid binding motif (KILRR). Novel antibiofilm peptide derivatives were modified by substituting hydrophobic amino acids at positions 5 or 7, and both, with positively charged lysines (L5K, L7K). These peptide derivatives were tested for antibiofilm and antimicrobial activities against biofilm-forming Staphylococcus epidermidis and multiple other microbes using crystal violet and broth microdilution assays, respectively. To assess their impact on mammalian cells, the toxicity of peptides was determined through hemolysis and cytotoxicity assays. The stability of candidate peptide, BiF2_5K7K, was assessed in human serum and its secondary structure in bacterial membrane-like environments was analyzed using circular dichroism. The action of BiF2_5K7K on planktonic S. epidermidis and its effect on biofilm cell viability were assessed via viable counting assays. Its biofilm inhibition mechanism was investigated through confocal laser scanning microscopy and transcription analysis. Additionally, its ability to eradicate mature biofilms was examined using colony counting. Finally, a preliminary evaluation involved coating a catheter with BiF2_5K7K to assess its preventive efficacy against S. epidermidis biofilm formation on the catheter and its surrounding area.</p><p><strong>Results: </strong>BiF2_5K7K, the modified antibiofilm peptide, exhibited dose-dependent antibiofilm activity against S. epidermidis. It inhibited biofilm formation at subinhibitory concentrations by altering S. epidermidis extracellular polysaccharide production and quorum-sensing gene expression. Additionally, it exhibited broad-spectrum antimicrobial activity and no significant hemolysis or toxicity against mammalian cell lines was observed. Its activity is retained when exposed to human serum. In bacterial membrane-like environments, this peptide formed an α-helix amphipathic structure. Within 4 h, a reduction in the number of S. epidermidis colonies was observed, demonstrating the fast action of this peptide. As a preliminary test, a BiF2_5K7K-coated catheter was able to prevent the development of S. epidermidis biofilm both on the catheter surface and in its surrounding area.</p><p><strong>Conclusions: </strong>Due to the safety and effectiveness of BiF2_5K7K, we suggest that this peptide be further developed to combat biofilm infections, particularly those
背景:由于生物膜的耐药性和治疗难度,生物膜相关感染是全球住院病人的一大难题,占人类所有细菌感染的60%。抗生物膜肽是最近出现的一种替代治疗方法,因为它们可以被有效设计,并以不同的模式抑制和根除生物膜:方法:利用模板辅助技术,从 18 种 α-helical 抗生物膜肽的保守序列中设计出一种新型抗生物膜肽 BiF,并通过与脂质结合基序(KILRR)杂交提高其活性。通过用带正电荷的赖氨酸(L5K、L7K)取代第 5 位或第 7 位以及这两个位置的疏水氨基酸,对新型抗生物膜肽衍生物进行了修饰。利用水晶紫法和肉汤微稀释法测试了这些肽衍生物对形成生物膜的表皮葡萄球菌和其他多种微生物的抗生物膜和抗菌活性。为了评估多肽对哺乳动物细胞的影响,还通过溶血和细胞毒性试验确定了多肽的毒性。评估了候选肽 BiF2_5K7K 在人血清中的稳定性,并利用圆二色性分析了其在细菌膜样环境中的二级结构。BiF2_5K7K 对浮游表皮葡萄球菌的作用及其对生物膜细胞活力的影响通过活力计数法进行了评估。通过共焦激光扫描显微镜和转录分析研究了其抑制生物膜的机制。此外,还使用菌落计数法检测了其根除成熟生物膜的能力。最后,在导管上涂上 BiF2_5K7K 进行了初步评估,以评估其对导管及其周围区域的表皮葡萄球菌生物膜形成的预防效果:结果:改良抗生物膜肽 BiF2_5K7K 对表皮葡萄球菌具有剂量依赖性抗生物膜活性。它通过改变表皮葡萄球菌胞外多糖的产生和法定量感应基因的表达,在亚抑制浓度下抑制生物膜的形成。此外,它还具有广谱抗菌活性,对哺乳动物细胞株没有明显的溶血或毒性。当暴露于人类血清中时,它的活性仍能保持。在类似细菌膜的环境中,这种肽形成了一种 α 螺旋两亲结构。在 4 小时内,观察到表皮葡萄球菌菌落数量减少,这证明了这种肽的快速作用。作为初步测试,涂有 BiF2_5K7K 的导管能够防止表皮葡萄球菌在导管表面及其周围形成生物膜:鉴于 BiF2_5K7K 的安全性和有效性,我们建议进一步开发这种多肽,以防治生物膜感染,尤其是由形成生物膜的表皮葡萄球菌引起的感染。
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引用次数: 0
Left knee septic monoarthritis in a pediatric patient due to shewanella putrefaciens: case report and literature review. 一名儿童患者的左膝化脓性单关节炎是由腐生雪旺菌引起的:病例报告和文献综述。
IF 4.6 2区 医学 Q1 MICROBIOLOGY Pub Date : 2024-05-10 DOI: 10.1186/s12941-024-00702-6
Nathalie Yepes Madrid, Luis Fernando Mejia, José Fernando Gomez Urrego

Background: Shewanella putrefaciens is a gram-negative, nonfermenting, oxidase-positive, hydrogen sulfide-producing bacillus and a halophilic bacterium, known for causing unusual infections in humans and often regarded as an opportunistic pathogen. Its diverse symptoms have a significant impact on human health, with 260 documented disorders reported in the literature over the last 40 years, highlighting its potential danger.

Case presentation: We present the case of a previously healthy 15-year-old male patient who sustained a self-inflicted sharp-object injury while working in the field, resulting in secondary septic monoarthritis due to Shewanella putrefaciens.

Conclusions: This case highlights the bacteriological and clinical characteristics, as well as the antibiogram, of Shewanella spp. Given the recent increase in notifications of Shewanella infections, predominantly by S. algae and S. putrefaciens, it is essential to consider these pathogens in patients with a history of contact with bodies of water. Special attention must be paid to their resistance patterns in patient management to prevent the development of intrinsic antimicrobial resistance.

背景:普氏希瓦菌(Shewanella putrefaciens)是一种革兰氏阴性、不发酵、氧化酶阳性、产硫化氢的杆菌和嗜盐细菌,以引起人类异常感染而闻名,通常被视为机会性病原体。它的症状多种多样,对人类健康有重大影响,在过去的 40 年中,文献报道了 260 种病症,突显了其潜在的危险性:我们介绍的病例是一名原本健康的 15 岁男性患者,他在野外工作时不慎被锐器所伤,导致继发性化脓性单关节炎,病原体是腐生雪旺菌:本病例强调了雪旺菌属的细菌学和临床特征以及抗生素谱。鉴于最近雪旺菌感染(主要是藻雪旺菌和腐生雪旺菌)的病例增多,对于有水体接触史的患者,必须考虑这些病原体。在患者管理中必须特别注意这些病原体的耐药性模式,以防止产生内在的抗菌药耐药性。
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引用次数: 0
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Annals of Clinical Microbiology and Antimicrobials
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