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MOLECULAR CHARACTERIZATION OF CARBAPENEMASE CO-PRODUCTION IN KLEBSIELLA PNEUMONIAE 肺炎克雷伯菌碳青霉烯酶共产的分子特征
IF 2.8 4区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2026-03-01 Epub Date: 2026-03-14 DOI: 10.1016/j.bjid.2026.104650
Patrícia Guedes Garcia , Ana Clara de Lelis Araújo , Alessandra Figueiredo de Castro Nassar , Lívia Mara Silva , Luciana Debortoli de Carvalho , Márcio Roberto Silva , Marcelo Silva Silvério , Olavo dos Santos Pereira Júnior , Romário Costa Fochat

Introduction/Objective

Carbapenem-resistant Klebsiella pneumoniae represents a serious public health threat due to its high prevalence and therapeutic difficulty. This resistance is often associated with the production of carbapenemases such as KPC, NDM, and OXA-48. The dissemination of these isolates in hospital environments requires continuous surveillance and strict infection control measures. In this context, this study aimed to investigate the prevalence and the genes encoding carbapenemases in carbapenem-resistant clinical isolates of K. pneumoniae from hospitalized patients, as well as to verify carbapenemase co-production in these isolates.

Methods

This is a cross-sectional study conducted between 2020 and 2023 at a public hospital located in the Zona da Mata region of Minas Gerais, Brazil. Carbapenem-resistant K. pneumoniae strains obtained from clinical samples were analyzed. Initial species identification was performed by phenotypic methods and subsequently confirmed by mass spectrometry. Screening for carbapenem resistance was conducted by phenotypic tests, and detection of the resistance genes blaKPC, blaNDM, blaOXA-48, blaIMP, and blaVIM was carried out by real-time polymerase chain reaction (qPCR). The study was approved by the Human Research Ethics Committee.

Results

A total of 67 carbapenem-resistant clinical isolates of K. pneumoniae were included, 30 from the years 2020 to 2022 and 37 from 2023. Molecular analysis revealed that 56.71% (n = 38) of isolates had only the blaKPC gene, while 10.44% (n = 7) expressed only the blaNDM gene. Co-production of blaKPC and blaNDM was identified in 31.35% (n = 21) of samples, and co-production of blaKPC and blaOXA-48 was detected in 1.5% (n = 1). It was observed that all co-production cases occurred in 2023, totaling 22 of the 37 isolates from that period, corresponding to 59.45% of the strains analyzed that year.

Conclusion

The detection of K. pneumoniae with co-production of carbapenemase genes demonstrates the complexity of this species’ resistance profile and its clinical relevance in the dissemination of carbapenem resistance. These findings reinforce the need for more effective control strategies, the maintenance of microbiological surveillance programs, and the continuous development of studies to support targeted clinical interventions.
前言/目的耐碳青霉烯肺炎克雷伯菌因其高流行率和治疗难度严重威胁公共卫生。这种耐药性通常与碳青霉烯酶的产生有关,如KPC、NDM和OXA-48。这些分离株在医院环境中的传播需要持续监测和严格的感染控制措施。在此背景下,本研究旨在调查来自住院患者的耐碳青霉烯类肺炎克雷伯菌临床分离株的患病率和编码碳青霉烯类酶的基因,并验证这些分离株中碳青霉烯类酶的共产。方法:这是一项横断面研究,于2020年至2023年在巴西米纳斯吉拉斯州Zona da Mata区的一家公立医院进行。对临床标本中获得的耐碳青霉烯肺炎克雷伯菌进行分析。最初的物种鉴定是通过表型方法进行的,随后通过质谱法证实。采用表型检测筛选碳青霉烯类耐药菌株,采用实时荧光定量pcr检测耐药基因blaKPC、blaNDM、blaxa -48、blaIMP和blaVIM。这项研究得到了人类研究伦理委员会的批准。结果共检出67株耐碳青霉烯类肺炎克雷伯菌临床分离株,其中2020 - 2022年30株,2023年37株。分子分析结果显示,56.71% (n = 38)的分离株只表达blaKPC基因,10.44% (n = 7)的分离株只表达blaNDM基因。31.35% (n = 21)的样品检测到blaKPC和blaNDM共产,1.5% (n = 1)的样品检测到blaKPC和blaOXA-48共产。所有合产病例均发生在2023年,37株分离株中有22株发生在该时期,占当年分析菌株的59.45%。结论联合产碳青霉烯酶基因的肺炎克雷伯菌的检测表明该菌耐药谱的复杂性及其在碳青霉烯酶耐药传播中的临床意义。这些发现强调需要更有效的控制策略,维持微生物监测计划,以及持续发展研究以支持有针对性的临床干预措施。
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引用次数: 0
PREVALENCE OF STAPHYLOCOCCUS AUREUS IN PUBLIC HOSPITALS IN MANAUS, AMAZONAS 亚马逊州马瑙斯市公立医院金黄色葡萄球菌患病率
IF 2.8 4区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2026-03-01 Epub Date: 2026-03-14 DOI: 10.1016/j.bjid.2026.104707
Caroline Sousa Martins de Almeida , Francielle Sousa Belém , Lucas de Souza Andrade , Cristiane Nazaré Fidelis Aparício , Ana Carolina Moura Xavier , Jackeline da Silva Luciano , Paula Taquita Serra , Ivanildes dos Santos Bastos , Patrícia Puccinelli Orlandi

Introduction

Staphylococcus aureus is an asymptomatic colonizer present in about 30% of the global population and is estimated to account for 17% of healthcare-associated infections (HAIs) worldwide. Due to its ability to form biofilms, this pathogen can survive for long periods on hospital surfaces, contributing to antimicrobial resistance. The objective of this study was to identify the prevalence of S. aureus in three public hospitals in Manaus, Amazonas.

Methods

Samples were collected from hospital surfaces using sterile swabs. They were inoculated in Brain Heart Infusion broth at 37°C for 24 hours, then isolated on selective Mannitol Salt Agar. Selected colonies underwent biochemical tests for species confirmation.

Results

A total of 997 samples from hospital surfaces were collected, of which 544 (54.56%) showed S. aureus growth. Hospital A (HA) had the highest prevalence, with 38.90% positive samples, followed by Hospital B (HB) with 33.39%, and Hospital C (HC) with 27.71%. Among hospital sectors, the wards and intensive care units (ICUs) showed the highest colonization rates. In HA, 46.23% of ward and 37.26% of ICU samples were positive. In HB, positivity was 44.75% in wards and 43.09% in ICUs. In HC, the ward showed the highest prevalence (65.56%) compared to other hospitals, while the ICU had 17.22%. The most frequently contaminated surfaces were patient beds (HA: 12.26%; HB: 18.23%; HC: 33.77%), floors (HA: 14.15%; HB: 13.81%; HC: 8.61%), and oxygen regulators (HA: 10.38%; HB: 19.89%; HC: 26.49%).

Conclusion

This study revealed a high prevalence of S. aureus on hospital surfaces, which is concerning as these surfaces can act as reservoirs, facilitating cross-transmission in the hospital environment. Epidemiological studies are essential to better understand the behavior of this bacterium and to develop new protocols and strategies to reduce its spread.
金黄色葡萄球菌是一种无症状的定植菌,约占全球人口的30%,据估计占全球卫生保健相关感染(HAIs)的17%。由于其形成生物膜的能力,这种病原体可以在医院表面存活很长时间,有助于抗菌素耐药性。本研究的目的是确定在玛瑙斯,亚马逊州三所公立医院的金黄色葡萄球菌的流行情况。方法采用无菌拭子法采集医院表面标本。将其接种于37℃的脑心灌注肉汤中24小时,然后在选择性甘露醇盐琼脂上分离。选定的菌落进行了物种确认的生化试验。结果共采集医院表面标本997份,其中544份(54.56%)有金黄色葡萄球菌生长。A医院(HA)阳性率最高,为38.90%,B医院(HB)次之,为33.39%,C医院(HC)为27.71%。在医院部门中,病房和重症监护病房(icu)的殖民化率最高。在HA, 46.23%的病区和37.26%的ICU样本呈阳性。HB在病房阳性率为44.75%,icu阳性率为43.09%。HC病房患病率最高,为65.56%,ICU为17.22%。最常见的污染表面是病床(HA: 12.26%; HB: 18.23%; HC: 33.77%)、地板(HA: 14.15%; HB: 13.81%; HC: 8.61%)和氧气调节器(HA: 10.38%; HB: 19.89%; HC: 26.49%)。结论金黄色葡萄球菌在医院表面的高流行率值得关注,因为这些表面可以作为宿主,促进医院环境中的交叉传播。流行病学研究对于更好地了解这种细菌的行为和制定减少其传播的新方案和策略至关重要。
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引用次数: 0
COST REDUCTION AND RESOURCE OPTIMIZATION: ECONOMIC EVALUATION OF AN ANTIMICROBIAL PROGRAM IN AN INFECTIOUS DISEASES HOSPITAL 降低成本与优化资源:某传染病医院抗菌项目的经济评价
IF 2.8 4区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2026-03-01 Epub Date: 2026-03-14 DOI: 10.1016/j.bjid.2026.104711
Lucas Mendes Feitosa Dias , Karine Kimberlly Rocha da Fonseca , Lílian Macambira Pinto , Evelyne Santana Girão

Introduction/Objective

The Antimicrobial Management Program (AMP) is an institutional strategy aimed at optimizing antimicrobial use in healthcare services, ensuring therapeutic efficacy, reducing adverse events associated with inappropriate use, preventing the selection of resistant microorganisms, and lowering unnecessary healthcare costs. In an infectious diseases hospital, patients often require intensive and prolonged antimicrobial use, making this setting particularly vulnerable to resistant bacteria and high expenditures on costly therapies. This study aimed to analyze the economic impact of the AMP on antimicrobial treatment costs in an infectious diseases hospital.

Methods

This is a descriptive and retrospective study based on AMP monitoring data collected in 2024 in a tertiary hospital specializing in infectious diseases. Information was obtained from program performance indicators, including planned versus actual antimicrobial expenditure and adherence to clinical stewardship interventions. The study was approved under protocol number 7.423.682 and CAAE 85396524.8.0000.5044.

Results

In 2024, projected antimicrobial expenditures were estimated at R$590,626.48. Through AMP intervention strategies, actual spending totaled R$298,503.35, resulting in direct savings of R$292,123.13 and an optimization rate of 50.54%. These results were achieved through interdisciplinary clinical audits, early treatment reassessments, and promotion of responsible use of broad-spectrum antimicrobials. The program also had a positive clinical impact, with infection cure rates of up to 27% in some months and hospital mortality rates below 26% among monitored patients.

Conclusion

The AMP proved effective in reducing antimicrobial expenditures in an infectious diseases hospital without compromising clinical outcomes. The savings of over R$290,000 in a single year demonstrate the strategy’s economic potential, particularly in high-complexity settings. Strengthening such initiatives is essential for the sustainability of healthcare systems and the fight against antimicrobial resistance.
抗菌药物管理计划(AMP)是一项旨在优化医疗服务中抗菌药物使用、确保治疗效果、减少与不当使用相关的不良事件、防止耐药微生物的选择和降低不必要的医疗成本的机构策略。在传染病医院,患者往往需要密集和长时间使用抗微生物药物,这使得这种环境特别容易受到耐药细菌的影响,而且治疗费用高昂。本研究旨在分析某传染病医院AMP对抗菌治疗费用的经济影响。方法采用描述性和回顾性研究方法,收集某三级感染性医院2024年AMP监测数据。从规划绩效指标中获得信息,包括计划与实际的抗菌药物支出和对临床管理干预措施的依从性。该研究已获批准,协议号为7.423.682,CAAE为85396524.8.0000.5044。结果2024年预计抗菌药物支出估计为590,626.48雷亚尔。通过AMP干预策略,实际支出共计298,503.35雷亚尔,直接节省292,123.13雷亚尔,优化率为50.54%。这些成果是通过跨学科临床审计、早期治疗再评估和促进负责任地使用广谱抗微生物药物取得的。该项目还产生了积极的临床影响,在某些月份,感染治愈率高达27%,在受监测的患者中,住院死亡率低于26%。结论AMP在不影响临床结果的情况下,有效降低了感染性疾病医院的抗菌药物支出。一年节省的成本超过29万雷亚尔,证明了该策略的经济潜力,特别是在高度复杂的环境中。加强此类举措对于卫生保健系统的可持续性和抗击抗菌素耐药性至关重要。
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引用次数: 0
INFECTIONS CAUSED BY NDM- AND NDM+KPC-PRODUCING ENTEROBACTERALES: EPIDEMIOLOGICAL PROFILE IN A UNIVERSITY HOSPITAL 产ndm -和ndm + kpc肠杆菌引起的感染:某大学医院的流行病学概况
IF 2.8 4区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2026-03-01 Epub Date: 2026-03-14 DOI: 10.1016/j.bjid.2026.104685
Rafael Amoroso Santos, Nathália de Lima Martins Abichabki, Nayara Maria Garcia, Renata Helena Candido Pocente, Denissani Aparecida Ferrari dos Santos Lima, Amaury Quaggio Neto, Lécio Rodrigues Ferreira, Natali Canelli Valim, Leonardo Neves de Andrade, Valdes Roberto Bollela, Cinara Silva Feliciano

Introduction/Objective

The production of New Delhi Metallo-β-lactamase (NDM) by Enterobacterales has a major impact on antimicrobial therapy, particularly in multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, significantly limiting treatment options. Additionally, the co-production of NDM and Klebsiella pneumoniae carbapenemase (KPC) has emerged and may result in pandrug-resistant phenotypes. This study aimed to describe the local epidemiology of infections caused by NDM- and NDM+KPC-producing Enterobacterales, correlating clinical and microbiological data.

Methods

Bacterial isolates producing NDM or co-producing NDM and KPC were analyzed from various clinical specimens (urine, tracheal aspirate, blood, surgical wounds) collected from patients admitted to a university hospital between January and June 2025. Detection of NDM and KPC was performed using an immunochromatographic assay for carbapenemases, and bacterial identification was carried out by MALDI-TOF. Clinical data were obtained through chart review.

Results

During the study period, 36 NDM-producing isolates and 9 NDM+KPC co-producing isolates were identified, comprising Klebsiella pneumoniae (n = 27), Klebsiella oxytoca (n = 1), Klebsiella variicola (n = 2), Enterobacter cloacae(n = 12), Escherichia coli (n = 1), and Kluyvera intermedia (n = 2). The majority (n = 16, 35%) were isolated from urine samples, followed by tracheal aspirates (n = 9, 20%). A total of 33 patients were affected, with a median age of 63 years; 42% (n = 14) were hospitalized in clinical wards and 21% (n = 7) in intensive care units. Five patients (15.2%) were immunosuppressed, and the overall mortality rate was 42% (n = 14).

Conclusion

A significant circulation of NDM-producing Enterobacterales was observed, mainly K. pneumoniae and E. cloacae, predominantly from urinary and tracheal aspirate samples. The detection of isolates co-producing NDM and KPC highlights the potential for dissemination of even broader resistance phenotypes, directly impacting available therapeutic options. These findings underscore the importance of active microbiological surveillance, strict infection control measures, and rational antimicrobial use to prevent the spread of these clinically and epidemiologically relevant strains.
肠杆菌生产新德里金属-β-内酰胺酶(NDM)对抗菌治疗产生重大影响,特别是对多药耐药(MDR)和广泛耐药(XDR)菌株,严重限制了治疗选择。此外,NDM和肺炎克雷伯菌碳青霉烯酶(KPC)的共同产生已经出现,并可能导致大范围耐药表型。本研究旨在描述产生NDM-和NDM+ kpc的肠杆菌引起的感染的当地流行病学,并将临床和微生物学数据相关联。方法对某大学附属医院于2025年1 - 6月收集的临床标本(尿液、气管吸出物、血液、手术伤口)中产生NDM或同时产生NDM和KPC的分离菌进行分析。采用碳青霉烯酶免疫层析法检测NDM和KPC,采用MALDI-TOF进行细菌鉴定。通过图表复习获得临床资料。ResultsDuring研究期间,36 NDM-producing隔离和9 NDM + KPC合拍隔离,包括肺炎克雷伯菌(n = 27),克雷伯氏菌oxytoca (n = 1),克雷伯氏菌variicola (n = 2),肠杆菌泄殖腔(n = 12),大肠杆菌(n = 1),和Kluyvera媒介物(n = 2)。大多数(n = 16,35%)是从尿液样本中分离出来的,其次是气管吸入物(n = 9,20%)。共有33例患者受到影响,中位年龄63岁;42% (n = 14)在临床病房住院,21% (n = 7)在重症监护病房住院。免疫抑制5例(15.2%),总死亡率为42% (n = 14)。结论产生ndm的肠杆菌以肺炎克雷伯菌和阴沟埃希菌为主,主要来自尿液和气管吸入样本。共同产生NDM和KPC的分离株的检测突出了传播更广泛耐药表型的潜力,直接影响现有的治疗选择。这些发现强调了积极的微生物监测、严格的感染控制措施和合理使用抗菌药物以防止这些临床和流行病学相关菌株传播的重要性。
{"title":"INFECTIONS CAUSED BY NDM- AND NDM+KPC-PRODUCING ENTEROBACTERALES: EPIDEMIOLOGICAL PROFILE IN A UNIVERSITY HOSPITAL","authors":"Rafael Amoroso Santos,&nbsp;Nathália de Lima Martins Abichabki,&nbsp;Nayara Maria Garcia,&nbsp;Renata Helena Candido Pocente,&nbsp;Denissani Aparecida Ferrari dos Santos Lima,&nbsp;Amaury Quaggio Neto,&nbsp;Lécio Rodrigues Ferreira,&nbsp;Natali Canelli Valim,&nbsp;Leonardo Neves de Andrade,&nbsp;Valdes Roberto Bollela,&nbsp;Cinara Silva Feliciano","doi":"10.1016/j.bjid.2026.104685","DOIUrl":"10.1016/j.bjid.2026.104685","url":null,"abstract":"<div><h3>Introduction/Objective</h3><div>The production of New Delhi Metallo-β-lactamase (NDM) by Enterobacterales has a major impact on antimicrobial therapy, particularly in multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, significantly limiting treatment options. Additionally, the co-production of NDM and <em>Klebsiella pneumoniae</em> carbapenemase (KPC) has emerged and may result in pandrug-resistant phenotypes. This study aimed to describe the local epidemiology of infections caused by NDM- and NDM+KPC-producing Enterobacterales, correlating clinical and microbiological data.</div></div><div><h3>Methods</h3><div>Bacterial isolates producing NDM or co-producing NDM and KPC were analyzed from various clinical specimens (urine, tracheal aspirate, blood, surgical wounds) collected from patients admitted to a university hospital between January and June 2025. Detection of NDM and KPC was performed using an immunochromatographic assay for carbapenemases, and bacterial identification was carried out by MALDI-TOF. Clinical data were obtained through chart review.</div></div><div><h3>Results</h3><div>During the study period, 36 NDM-producing isolates and 9 NDM+KPC co-producing isolates were identified, comprising <em>Klebsiella pneumoniae</em> (n = 27), <em>Klebsiella oxytoca</em> (n = 1), <em>Klebsiella variicola</em> (n = 2), <em>Enterobacter cloacae</em>(n = 12), <em>Escherichia coli</em> (n = 1), and <em>Kluyvera intermedia</em> (n = 2). The majority (n = 16, 35%) were isolated from urine samples, followed by tracheal aspirates (n = 9, 20%). A total of 33 patients were affected, with a median age of 63 years; 42% (n = 14) were hospitalized in clinical wards and 21% (n = 7) in intensive care units. Five patients (15.2%) were immunosuppressed, and the overall mortality rate was 42% (n = 14).</div></div><div><h3>Conclusion</h3><div>A significant circulation of NDM-producing Enterobacterales was observed, mainly <em>K. pneumoniae</em> and <em>E. cloacae</em>, predominantly from urinary and tracheal aspirate samples. The detection of isolates co-producing NDM and KPC highlights the potential for dissemination of even broader resistance phenotypes, directly impacting available therapeutic options. These findings underscore the importance of active microbiological surveillance, strict infection control measures, and rational antimicrobial use to prevent the spread of these clinically and epidemiologically relevant strains.</div></div>","PeriodicalId":56327,"journal":{"name":"Brazilian Journal of Infectious Diseases","volume":"30 ","pages":"Article 104685"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147453964","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
CONSERVED STRUCTURAL INTERACTIONS SUGGEST POTENTIAL BINDING OF N-ACETYLCYSTEINE TO THE UREASE OF CLINICAL ACINETOBACTER ISOLATES 保守的结构相互作用提示n -乙酰半胱氨酸与临床分离不动杆菌脲酶的潜在结合
IF 2.8 4区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2026-03-01 Epub Date: 2026-03-14 DOI: 10.1016/j.bjid.2026.104686
Ana Lídia Pires de Assis Pinto, João Pedro Vasques da Conceição, Fabio Faria da Mota

Introduction

N-acetylcysteine (NAC), a mucolytic widely used in medical practice for the treatment of viral infections, has also shown antimicrobial properties through the inhibition of the bacterial urease of Proteus mirabilis [1]. Urease is a nickel-dependent enzyme that hydrolyzes urea into ammonia and carbon dioxide, promoting bacterial persistence through an increase in local pH. In Acinetobacter spp., a genus frequently associated with multidrug-resistant infections, urease is a virulence factor critical for persistence in macrophages during lung infection [2].

Objective

This study evaluated the binding of NAC to the immature (apoenzyme) and mature (holoenzyme) forms of urease from clinical Acinetobacter isolates.

Methods

The structures were modeled using AlphaFold3 (apo) and AlphaFill (holo), the latter including Ni²⁺ cofactors in the active site. NAC was submitted to molecular docking with AutoDock Vina (v1.2.7) in both forms. The interactions were analyzed in PoseView, and the conservation of residues was verified by multiple alignment of 233 sequences of clinical isolates using MAFFT (v7.505).

Results

Docking simulations suggested similar binding affinities for the apoenzyme and holoenzyme, –4.7 kcal/mol and –4.4 kcal/mol, respectively. NAC interacted with an overlapping set of residues in both forms, including His133, His135, His218, His245, His271, and Ala362, mainly through hydrogen bonds and salt bridges. In the apoenzyme, a salt bridge was observed with Lys216, while in the holoenzyme, NAC formed a specific hydrogen bond with Asp359 and coordinated both Ni²⁺ ions — an interaction absent in the apo form. These subtle differences reflect the structural changes associated with enzymatic maturation, but overall, the binding mode was highly conserved. The multiple alignment of 233 Acinetobacter spp. urease sequences from clinical isolates confirmed that all interacting residues are highly conserved, reinforcing their functional importance.

Conclusion

The ability of NAC to bind to structurally essential residues of the active site of urease from clinical Acinetobacter spp. suggests the potential repositioning of this drug for the attenuation of virulence in clinical infections by multidrug-resistant Acinetobacter baumannii.
n -乙酰半胱氨酸(NAC)是一种广泛用于治疗病毒感染的黏液解液,通过抑制奇异变形杆菌(Proteus mirabilis)[1]的细菌脲酶也显示出抗菌特性。脲酶是一种依赖镍的酶,可将尿素水解成氨和二氧化碳,通过增加局部ph来促进细菌的持久性。在不动杆菌属中,脲酶是肺部感染期间巨噬细胞持久性的关键毒力因子。不动杆菌属经常与多重耐药感染相关。目的研究临床分离的不动杆菌未成熟(脱酶)和成熟(全酶)脲酶与NAC的结合。方法采用AlphaFold3 (apo)和AlphaFill (holo)对结构进行建模,后者在活性位点包含Ni 2 +辅因子。NAC以两种形式与AutoDock v1.2.7进行分子对接。利用MAFFT (v7.505)软件对233个临床分离菌株序列进行多重比对,验证了残基的保守性。结果对接模拟表明,脱酶和全酶的结合亲和力相似,分别为-4.7 kcal/mol和-4.4 kcal/mol。NAC主要通过氢键和盐桥与包括His133、His135、His218、His245、His271和Ala362在内的重叠残基相互作用。在载脂蛋白酶中,与Lys216形成了盐桥,而在全酶中,NAC与Asp359形成了一个特定的氢键,并协调了两个Ni 2 +离子,这是载脂蛋白形式中没有的一种相互作用。这些细微的差异反映了与酶成熟相关的结构变化,但总体而言,结合模式是高度保守的。对233个临床分离不动杆菌脲酶序列的多重比对证实,所有相互作用残基都是高度保守的,增强了它们的功能重要性。结论NAC能够与临床不动杆菌脲酶活性位点的结构必需残基结合,表明该药物有可能重新定位,以降低临床感染多重耐药鲍曼不动杆菌的毒力。
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引用次数: 0
IMPACT OF THE COVID-19 PANDEMIC ON ANTIMICROBIAL CONSUMPTION IN BRAZIL: A RETROSPECTIVE STUDY FROM 2014 TO 2021 2019冠状病毒病大流行对巴西抗微生物药物消费的影响:2014年至2021年的回顾性研究
IF 2.8 4区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2026-03-01 Epub Date: 2026-03-14 DOI: 10.1016/j.bjid.2026.104674
Matheus Negri Boschieiro , Nathalia Sansone , Laura Ribeiro Matos , Lucas Silva Mello , Luiz Felipe Azevedo Marques , Fernando Augusto Lima Marson

Introduction/Objective

During the COVID-19 pandemic, an increase in hospital use of these medications was observed, raising concerns regarding their impact on antimicrobial resistance. The objective of this study was to evaluate antimicrobial consumption in Brazil during the COVID-19 pandemic period.

Methods

Retrospective study. Data on antimicrobial consumption were obtained from the National Controlled Products Management System. Consumption was calculated in annual Defined Daily Doses per 1,000,000 inhabitant-days (DDD/1,000,000 inhabitant-days), using the formula: (total weight dispensed in the year, in g × 1,000,000) ÷ (DDD of the substance, in g × Brazilian population of the year × 365). Multiple linear regression was performed to assess the association between consumption and the pandemic, including an interaction term between the month of dispensing and the pandemic period (2014–2019 considered pre-pandemic and 2020 onward as post-pandemic). Results were expressed as estimates with 95% confidence intervals and a significance level of α < 0.05.

Results

The following antimicrobials were included: amoxicillin, amoxicillin-clavulanic acid, azithromycin, ceftriaxone, chloramphenicol, ciprofloxacin, clarithromycin, clindamycin, doxycycline, erythromycin, levofloxacin, sulfamethoxazole-trimethoprim, tetracycline, and vancomycin. The highest DDD value was observed for azithromycin in 2017 (2,305.13 per 1,000,000 inhabitant-days), followed by amoxicillin-clavulanic acid in 2019 (1,090.22) and amoxicillin in 2017 (1,079.20). In 2020, ceftriaxone (+175.1%), meropenem (+55.2%), and clindamycin (+23.6%) showed increased consumption compared with 2019, whereas erythromycin (−91.3%), clarithromycin (−73.5%), and amoxicillin (−59.9%) exhibited the greatest decreases. In 2021, ceftriaxone (+212.4%) consumption further increased, while erythromycin (−86.9%), clarithromycin (−73.0%), and amoxicillin (−61.0%) maintained a declining trend. In multiple linear regression, the model was statistically significant (p < 0.05) for amoxicillin, azithromycin, chloramphenicol, ciprofloxacin, clarithromycin, doxycycline, erythromycin, tetracycline, vancomycin, and meropenem. However, there was no statistically significant interaction between consumption and the pandemic period in any model.

Conclusion

An increase in the consumption of certain antimicrobials was observed during the post-pandemic period. However, the findings do not indicate a statistically significant association between the COVID-19 pandemic and national antimicrobial consumption.
在2019冠状病毒病大流行期间,观察到医院使用这些药物的情况有所增加,这引起了人们对其对抗菌素耐药性影响的担忧。本研究的目的是评估巴西在COVID-19大流行期间的抗微生物药物消费情况。MethodsRetrospective研究。抗菌药物消费数据来自国家受控产品管理系统。消耗量以每100万居民日的年度定义日剂量(DDD/ 100万居民日)计算,使用公式:(一年中分配的总重量,单位为g × 1,000,000)÷(该物质的DDD,单位为g × 巴西当年人口 × 365)。使用多元线性回归来评估消费量与大流行之间的关联,包括分配月份与大流行期间之间的相互作用项(2014-2019年被视为大流行前,2020年以后被视为大流行后)。结果以95%置信区间的估计值表示,显著性水平为α <; 0.05。结果抗菌药物包括:阿莫西林、阿莫西林-克拉维酸、阿奇霉素、头孢曲松、氯霉素、环丙沙星、克拉霉素、克林霉素、多西环素、红霉素、左氧氟沙星、磺胺甲恶唑-甲氧苄啶、四环素、万古霉素。阿奇霉素的DDD值在2017年最高(2305.13 / 100万居民日),其次是阿莫西林-克拉维酸(1090.22 / 100万居民日)和阿莫西林(1079.20 / 100万居民日)。与2019年相比,2020年头孢曲松(+175.1%)、美罗培南(+55.2%)和克林霉素(+23.6%)的消费量增加,红霉素(- 91.3%)、克拉霉素(- 73.5%)和阿莫西林(- 59.9%)的消费量下降幅度最大。2021年头孢曲松(+212.4%)用量进一步增加,红霉素(- 86.9%)、克拉霉素(- 73.0%)、阿莫西林(- 61.0%)用量保持下降趋势。在多元线性回归中,阿莫西林、阿奇霉素、氯霉素、环丙沙星、克拉霉素、多西环素、红霉素、四环素、万古霉素、美罗培南的模型具有统计学意义(p < 0.05)。然而,在任何模型中,消费与大流行时期之间都没有统计学上显著的相互作用。结论大流行后,某些抗微生物药物的消费量有所增加。然而,研究结果并未表明COVID-19大流行与国家抗菌药物消费之间存在统计学上显著的关联。
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引用次数: 0
ACTIVITY OF NEW ANTIMICROBIALS AGAINST MULTIDRUG-RESISTANT CLINICAL ISOLATES OF KLEBSIELLA PNEUMONIAE AND ACINETOBACTER BAUMANNII 新型抗菌剂对肺炎克雷伯菌和鲍曼不动杆菌多重耐药临床分离株的活性
IF 2.8 4区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2026-03-01 Epub Date: 2026-03-14 DOI: 10.1016/j.bjid.2026.104638
Eduardo Alexandrino Medeiros, Karen de Castro Bauab, Felipe Alberto Lei, Caio de Castro Novais, Samily Aquino de Sá Oliveira, Josiane Trevisol Leal, Diego Cassola Pronunciato, Diogo Boldin Ferreira

Introduction/Objective

Given the scarcity, or even absence, of effective therapies for the treatment of infections caused by multidrug-resistant (MDR) K. pneumoniae and/or A. baumannii in Brazil, combinations of β-lactams with next-generation β-lactamase inhibitors and tetracycline derivatives have emerged as promising antimicrobials.

Objective

To evaluate the in vitro activity of new antimicrobials against MDR isolates obtained from patients hospitalized in ICUs of six hospitals in the metropolitan region of São Paulo.

Methods

A total of 121 isolates of K. pneumoniae and 27 of A. baumannii, prospectively collected from patients hospitalized in six ICUs of the metropolitan region of São Paulo between 08/01/2023 and 10/31/2024, resistant to carbapenems, were analyzed. MICs for polymyxin B/E (POL), omadacycline (OMC), and eravacycline (ERV) were determined by broth microdilution (Sensititre, Thermo Fisher). For K. pneumoniae, 118 isolates without evidence of metallo-β-lactamase production were additionally tested for ceftazidime-avibactam (CZA), imipenem-relebactam (IMR), and meropenem-vaborbactam (MEV). Resistance genes of 55 K. pneumoniae and 21 A. baumannii were correlated with phenotypes.

Results

The susceptibility rates of K. pneumoniae to CZA, IMR, and MEV were 87.29%, 74.58%, and 82.20%, respectively. Among the 59 isolates resistant to amikacin (AMI) and POL, these rates were 96.91%, 75.86%, and 82.76%. Applying FDA breakpoints, 6 isolates (4.96%) were resistant to OMC (MIC > 8 mg/L) and 12 (9.92%) were intermediate (8 mg/L). Even among AMI/POL-resistant isolates, OMC susceptibility was 91.53%. For ERV, the MIC₉₀ was 1 mg/L in the overall group and 2 mg/L among resistant isolates. Of the 55 genomes analyzed, 92.73% carried blaKPC-2, 3.64% blaNDM-1, and 1.82% both. Two isolates with blaNDM-1 showed favorable MICs for ERV (0.5 mg/L) and OMC (≤ 4 mg/L). In A. baumannii, MIC₅₀/MIC₉₀ values were 2/8 mg/L for OMC and 0.5/2 mg/L for ERV. Among the 10 isolates resistant to POL, OMC showed an increased MIC₉₀ to 8 mg/L, but ERV maintained a profile similar to the overall group.

Conclusion

K. pneumoniae strains showed excellent activity to CZA, IMR, and MEV. MDR K. pneumoniae and A. baumannii strains were also susceptible to OMC and ERV, including subgroups resistant to POL, reinforcing the potential of these drugs as therapeutic options in highly resistant settings such as Brazilian ICUs.
鉴于巴西缺乏甚至缺乏治疗多药耐药(MDR)肺炎克雷伯菌和/或鲍曼芽胞杆菌引起的感染的有效疗法,β-内酰胺类药物与下一代β-内酰胺酶抑制剂和四环素衍生物的联合应用已成为一种有前景的抗菌剂。目的评价圣保罗大都市区6家医院重症监护病房患者的耐多药分离株的体外抗菌活性。方法对2023年8月1日至2024年10月31日期间圣保罗市区6个icu收治的碳青霉烯类耐药患者中肺炎克雷伯菌121株和鲍曼不稳定杆菌27株进行分析。多粘菌素B/E (POL)、奥马达环素(OMC)和依拉瓦环素(ERV)的mic采用微量肉汤稀释法(Sensititre, Thermo Fisher)测定。对肺炎克雷伯菌,118株无金属β-内酰胺酶产生证据的分离株进行了头孢他啶-阿维巴坦(CZA)、亚胺培南-乐巴坦(IMR)和美罗培南-瓦博巴坦(MEV)的检测。55株肺炎克雷伯菌和21株鲍曼不动杆菌的耐药基因与表型相关。结果肺炎克雷伯菌对CZA、IMR和MEV的易感性分别为87.29%、74.58%和82.20%。59株菌株对阿米卡星(AMI)和POL的耐药率分别为96.91%、75.86%和82.76%。应用FDA断点,6株(4.96%)对OMC (MIC > 8mg /L)耐药,12株(9.92%)为中间耐药(8mg /L)。即使在AMI/ pol耐药菌株中,OMC敏感性也为91.53%。对于ERV,整个组的MIC₉0为1 mg/L,耐药菌株的MIC₉0为2 mg/L。在分析的55个基因组中,92.73%携带blaKPC-2, 3.64%携带blaNDM-1, 1.82%携带blaKPC-2和blakpc -1。两株blaNDM-1菌株对ERV (0.5 mg/L)和OMC(≤4 mg/L)的mic均表现良好。在鲍曼弧菌中,MIC₅0 /MIC₉0值为OMC的2/ 8mg /L和ERV的0.5/ 2mg /L。在10株对POL耐药的分离株中,OMC的MIC值升高至8 mg/L,而ERV的MIC值与整体组相似。肺炎菌株对CZA、IMR和MEV具有良好的活性。耐多药肺炎克雷伯菌和鲍曼不动杆菌菌株也对OMC和ERV敏感,包括对POL耐药的亚群,这加强了这些药物在巴西icu等高度耐药环境中作为治疗选择的潜力。
{"title":"ACTIVITY OF NEW ANTIMICROBIALS AGAINST MULTIDRUG-RESISTANT CLINICAL ISOLATES OF KLEBSIELLA PNEUMONIAE AND ACINETOBACTER BAUMANNII","authors":"Eduardo Alexandrino Medeiros,&nbsp;Karen de Castro Bauab,&nbsp;Felipe Alberto Lei,&nbsp;Caio de Castro Novais,&nbsp;Samily Aquino de Sá Oliveira,&nbsp;Josiane Trevisol Leal,&nbsp;Diego Cassola Pronunciato,&nbsp;Diogo Boldin Ferreira","doi":"10.1016/j.bjid.2026.104638","DOIUrl":"10.1016/j.bjid.2026.104638","url":null,"abstract":"<div><h3>Introduction/Objective</h3><div>Given the scarcity, or even absence, of effective therapies for the treatment of infections caused by multidrug-resistant (MDR) <em>K. pneumoniae</em> and/or <em>A. baumannii</em> in Brazil, combinations of β-lactams with next-generation β-lactamase inhibitors and tetracycline derivatives have emerged as promising antimicrobials.</div></div><div><h3>Objective</h3><div>To evaluate the <em>in vitro</em> activity of new antimicrobials against MDR isolates obtained from patients hospitalized in ICUs of six hospitals in the metropolitan region of São Paulo.</div></div><div><h3>Methods</h3><div>A total of 121 isolates of <em>K. pneumoniae</em> and 27 of <em>A. baumannii</em>, prospectively collected from patients hospitalized in six ICUs of the metropolitan region of São Paulo between 08/01/2023 and 10/31/2024, resistant to carbapenems, were analyzed. MICs for polymyxin B/E (POL), omadacycline (OMC), and eravacycline (ERV) were determined by broth microdilution (Sensititre, Thermo Fisher). For <em>K. pneumoniae</em>, 118 isolates without evidence of metallo-β-lactamase production were additionally tested for ceftazidime-avibactam (CZA), imipenem-relebactam (IMR), and meropenem-vaborbactam (MEV). Resistance genes of 55 <em>K. pneumoniae</em> and 21 <em>A. baumannii</em> were correlated with phenotypes.</div></div><div><h3>Results</h3><div>The susceptibility rates of <em>K. pneumoniae</em> to CZA, IMR, and MEV were 87.29%, 74.58%, and 82.20%, respectively. Among the 59 isolates resistant to amikacin (AMI) and POL, these rates were 96.91%, 75.86%, and 82.76%. Applying FDA breakpoints, 6 isolates (4.96%) were resistant to OMC (MIC &gt; 8 mg/L) and 12 (9.92%) were intermediate (8 mg/L). Even among AMI/POL-resistant isolates, OMC susceptibility was 91.53%. For ERV, the MIC₉₀ was 1 mg/L in the overall group and 2 mg/L among resistant isolates. Of the 55 genomes analyzed, 92.73% carried blaKPC-2, 3.64% blaNDM-1, and 1.82% both. Two isolates with blaNDM-1 showed favorable MICs for ERV (0.5 mg/L) and OMC (≤ 4 mg/L). In <em>A. baumannii</em>, MIC₅₀/MIC₉₀ values were 2/8 mg/L for OMC and 0.5/2 mg/L for ERV. Among the 10 isolates resistant to POL, OMC showed an increased MIC₉₀ to 8 mg/L, but ERV maintained a profile similar to the overall group.</div></div><div><h3>Conclusion</h3><div><em>K. pneumoniae</em> strains showed excellent activity to CZA, IMR, and MEV. MDR <em>K. pneumoniae</em> and <em>A. baumannii</em> strains were also susceptible to OMC and ERV, including subgroups resistant to POL, reinforcing the potential of these drugs as therapeutic options in highly resistant settings such as Brazilian ICUs.</div></div>","PeriodicalId":56327,"journal":{"name":"Brazilian Journal of Infectious Diseases","volume":"30 ","pages":"Article 104638"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454125","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 AZTREONAM-AVIBACTAM AGAINST CLINICAL ISOLATES OF ENTEROBACTERALES COLLECTED IN BRAZIL FOR THE ATLAS SURVEILLANCE PROGRAM, 2018–2023 2018-2023年巴西地图集监测项目收集的aztreonam-avibactam对临床分离肠杆菌的体外活性研究
IF 2.8 4区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2026-03-01 Epub Date: 2026-03-14 DOI: 10.1016/j.bjid.2026.104639
Lorena Cristina Correa Fehlberg, Camilla Natal De Gaspari, Daniela V Pachito

Introduction

Aztreonam-avibactam (ATM-AVI) was developed for the treatment of infections caused by Enterobacterales, particularly carbapenem-resistant isolates that produce metallo-β-lactamases (MBLs). Aztreonam is stable to hydrolysis by MBLs, while avibactam inhibits class A and C β-lactamases, which may also be co-produced with MBLs that inactivate aztreonam. In this study, the in vitro activity of ATM-AVI was evaluated against clinical isolates of Enterobacterales, both MBL producers and non-producers, collected as part of the global ATLAS surveillance program.

Methods

A total of 3151 non-duplicate Enterobacterales isolates collected from different infection sites in Brazilian hospitals between 2018 and 2023 were evaluated. Susceptibility testing was performed using broth microdilution. Antimicrobial susceptibility profiles were interpreted according to BrCAST (2025) breakpoints, including the established breakpoint for ATM-AVI of > 4 mg/L. Carbapenemase-encoding genes were investigated by PCR followed by sequencing.

Results

The majority of Enterobacterales species evaluated were Klebsiella pneumoniae (36.0%; n = 1137), followed by Escherichia coli (31.6%; n = 998) and Enterobacter sp. (12.6%; n = 399). Overall, ATM-AVI inhibited 100% of isolates (MIC50/90, 0.06/0.25 mg/L), including those producing carbapenemases (588/960 isolates tested [61.2%]). Overall susceptibility to colistin (MIC50/90, 0.25/>8 mg/L), meropenem (MIC50/90, ≤ 0.06/> 16 mg/L), cefepime (MIC50/90, ≤ 0.125/> 32 mg/L), and aztreonam (MIC50/90, 0.25/> 64 mg/L) was 85.7%, 80.6%, 58.4%, and 56.9%, respectively. Among the 960 isolates tested for carbapenemases, 119 (12.4%) were positive for NDM-1 and 492 (51.2%) for KPC. Twenty-five isolates showed coproduction of two carbapenemases, 24 with KPC-2+NDM-1 and one with KPC-2+IMP-1. All 492 KPC-positive isolates were 100% and 94.72% susceptible to ATM-AVI and ceftazidime-avibactam, respectively.

Conclusion

ATM-AVI demonstrated excellent in vitro activity, inhibiting 100% of Enterobacterales isolates, both carbapenemase producers and non-producers, including MBLs. Antibiotics that retain activity against MBL-producing bacteria represent an urgent medical need, especially given the rising prevalence of severe infections caused by these difficult-to-treat microorganisms.
aztreonam -avibactam (ATM-AVI)被开发用于治疗肠杆菌引起的感染,特别是产生金属β-内酰胺酶(MBLs)的碳青霉烯耐药分离株。氨曲南对mbl的水解是稳定的,而阿维巴坦抑制A类和C类β-内酰胺酶,这也可能与使氨曲南失活的mbl共同产生。在这项研究中,我们对作为全球ATLAS监测计划的一部分收集的肠杆菌临床分离株(MBL产生菌和非产生菌)进行了体外活性评估。方法对2018 - 2023年在巴西医院不同感染部位采集的3151株非重复肠杆菌进行分析。采用肉汤微量稀释法进行药敏试验。根据BrCAST(2025)断点对抗菌药物敏感性谱进行解释,包括建立的ATM-AVI断点为4 mg/L。碳青霉烯酶编码基因通过PCR和测序进行研究。结果评估的肠杆菌种类以肺炎克雷伯菌(36.0%,n = 1137)最多,其次是大肠杆菌(31.6%,n = 998)和肠杆菌(12.6%,n = 399)。总体而言,ATM-AVI抑制100%的分离株(MIC50/90, 0.06/0.25 mg/L),包括产生碳青霉烯酶的分离株(588/960株检测[61.2%])。对粘菌素(MIC50/90, 0.25/>8 mg/L)、美罗培南(MIC50/90,≤0.06/> 16 mg/L)、头孢吡肟(MIC50/90,≤0.125/> 32 mg/L)、氨曲南(MIC50/90, 0.25/> 64 mg/L)的总敏感性分别为85.7%、80.6%、58.4%、56.9%。960株碳青霉烯酶检测菌株中,NDM-1阳性119株(12.4%),KPC阳性492株(51.2%)。25株分离株显示两种碳青霉烯酶共产,其中24株与KPC-2+NDM-1共产,1株与KPC-2+IMP-1共产。492株kpc阳性菌株对ATM-AVI和头孢他啶-阿维巴坦的敏感性分别为100%和94.72%。结论atm - avi具有良好的体外活性,对产碳青霉烯酶和非产碳青霉烯酶的肠杆菌具有100%的抑制作用,包括MBLs。对产生mbl的细菌保持活性的抗生素是迫切的医疗需求,特别是考虑到由这些难以治疗的微生物引起的严重感染日益流行。
{"title":"IN VITRO ACTIVITY OF AZTREONAM-AVIBACTAM AGAINST CLINICAL ISOLATES OF ENTEROBACTERALES COLLECTED IN BRAZIL FOR THE ATLAS SURVEILLANCE PROGRAM, 2018–2023","authors":"Lorena Cristina Correa Fehlberg,&nbsp;Camilla Natal De Gaspari,&nbsp;Daniela V Pachito","doi":"10.1016/j.bjid.2026.104639","DOIUrl":"10.1016/j.bjid.2026.104639","url":null,"abstract":"<div><h3>Introduction</h3><div>Aztreonam-avibactam (ATM-AVI) was developed for the treatment of infections caused by Enterobacterales, particularly carbapenem-resistant isolates that produce metallo-β-lactamases (MBLs). Aztreonam is stable to hydrolysis by MBLs, while avibactam inhibits class A and C β-lactamases, which may also be co-produced with MBLs that inactivate aztreonam. In this study, the <em>in vitro</em> activity of ATM-AVI was evaluated against clinical isolates of Enterobacterales, both MBL producers and non-producers, collected as part of the global ATLAS surveillance program.</div></div><div><h3>Methods</h3><div>A total of 3151 non-duplicate Enterobacterales isolates collected from different infection sites in Brazilian hospitals between 2018 and 2023 were evaluated. Susceptibility testing was performed using broth microdilution. Antimicrobial susceptibility profiles were interpreted according to BrCAST (2025) breakpoints, including the established breakpoint for ATM-AVI of &gt; 4 mg/L. Carbapenemase-encoding genes were investigated by PCR followed by sequencing.</div></div><div><h3>Results</h3><div>The majority of Enterobacterales species evaluated were <em>Klebsiella pneumoniae</em> (36.0%; n = 1137), followed by <em>Escherichia coli</em> (31.6%; n = 998) and <em>Enterobacter</em> sp. (12.6%; n = 399). Overall, ATM-AVI inhibited 100% of isolates (MIC50/90, 0.06/0.25 mg/L), including those producing carbapenemases (588/960 isolates tested [61.2%]). Overall susceptibility to colistin (MIC50/90, 0.25/&gt;8 mg/L), meropenem (MIC50/90, ≤ 0.06/&gt; 16 mg/L), cefepime (MIC50/90, ≤ 0.125/&gt; 32 mg/L), and aztreonam (MIC50/90, 0.25/&gt; 64 mg/L) was 85.7%, 80.6%, 58.4%, and 56.9%, respectively. Among the 960 isolates tested for carbapenemases, 119 (12.4%) were positive for NDM-1 and 492 (51.2%) for KPC. Twenty-five isolates showed coproduction of two carbapenemases, 24 with KPC-2+NDM-1 and one with KPC-2+IMP-1. All 492 KPC-positive isolates were 100% and 94.72% susceptible to ATM-AVI and ceftazidime-avibactam, respectively.</div></div><div><h3>Conclusion</h3><div>ATM-AVI demonstrated excellent <em>in vitro</em> activity, inhibiting 100% of Enterobacterales isolates, both carbapenemase producers and non-producers, including MBLs. Antibiotics that retain activity against MBL-producing bacteria represent an urgent medical need, especially given the rising prevalence of severe infections caused by these difficult-to-treat microorganisms.</div></div>","PeriodicalId":56327,"journal":{"name":"Brazilian Journal of Infectious Diseases","volume":"30 ","pages":"Article 104639"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454126","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
ANALYSIS OF IN VITRO ACTIVITY OF CEFTAZIDIME-AVIBACTAM AGAINST CLINICAL ISOLATES OF PSEUDOMONAS AERUGINOSA COLLECTED FROM BRAZILIAN CENTERS FOR THE ATLAS SURVEILLANCE PROGRAM, 2018-2023 头孢他啶-阿维巴坦对巴西地图集监测中心2018-2023年铜绿假单胞菌临床分离株的体外活性分析
IF 2.8 4区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2026-03-01 Epub Date: 2026-03-14 DOI: 10.1016/j.bjid.2026.104629
Lorena Cristina Correa Fehlberg, Camilla Natal De Gaspari, Daniela V Pachito

Introduction

Pseudomonas aeruginosa is a pathogen that causes severe infections that are difficult to treat, as this bacterium can express multiple resistance mechanisms, in addition to its intrinsically limited susceptibility to many antibiotics. In this study, the in vitro activity of ceftazidime-avibactam was evaluated against clinical isolates of P. aeruginosa, both carbapenemase-producing and non-producing, collected as part of the global ATLAS surveillance program.

Methods

A total of 1239 non-duplicate P. aeruginosa isolates were evaluated, collected from different infection sites in hospitals across Brazil between 2018 and 2023. Susceptibility testing was performed using broth microdilution. The antimicrobial susceptibility profile was analyzed according to the breakpoints established by BrCAST (2025). The search for carbapenemase-encoding genes was performed by PCR followed by sequencing. Results Ceftazidime-avibactam (90.0% susceptible; MIC50/90, 2.0/8.0 mg/L) and colistin (99.8% susceptible; MIC50/90, 1.0/1.0 mg/L) were the antibiotics with the best in vitro activity. Approximately 70% of isolates tested for imipenem, cefepime, ceftazidime, and piperacillin-tazobactam were classified as susceptible with increased exposure, according to BrCAST criteria (range 68.7% to 74.5%). Susceptibility to ceftolozane-tazobactam was 84.3% (MIC50/90, 1.0/32.0 mg/L), but this antibiotic was evaluated in only 949/1239 isolates. Resistance gene screening was performed on 153 isolates, of which 17 (11%) were blaKPC-2 producers (4 also coproduced blaGES-1). The beta-lactamases found in 22 (18%) of the 123 ceftazidime-avibactam resistant P. aeruginosa isolates were: NDM-1 (n = 5), KPC-2 (n = 5), VIM-2 (n = 5), SPM-1 (n = 1), SPM-1+GES-1 (n = 1), IMP-16 (n = 1), IMP-56 (n = 1), KPC-2+GES-1 (n = 1), NDM-1+VEB-9 (n = 1), and NDM-1+VEB-14 (n = 1).

Conclusion

The results demonstrated that both ceftazidime-avibactam and ceftolozane-tazobactam maintain excellent in vitro activity (> 80%) against clinical isolates of P. aeruginosa. Although the presence of carbapenemases was relatively low among the isolates studied, ceftazidime-avibactam was 5 times more potent (MIC90) compared to ceftolozane-tazobactam, which may be partly explained by the presence of these beta-lactamases identified in the evaluated isolates.
铜绿假单胞菌(pseudomonas aeruginosa)是一种引起严重感染且难以治疗的病原体,因为这种细菌除了对许多抗生素固有的有限敏感性外,还可以表达多种耐药机制。在这项研究中,头孢他啶-阿维巴坦对产碳青霉烯酶和不产碳青霉烯酶的铜绿假单胞菌临床分离株的体外活性进行了评估,这些分离株是作为全球ATLAS监测计划的一部分收集的。方法对2018 - 2023年在巴西各医院不同感染地点采集的1239株非重复铜绿假单胞菌进行分析。采用肉汤微量稀释法进行药敏试验。根据BrCAST(2025)建立的断点分析耐药谱。碳青霉烯酶编码基因通过PCR和测序进行搜索。结果头孢他啶-阿维巴坦(90.0%,MIC50/90, 2.0/8.0 mg/L)和粘菌素(99.8%,MIC50/90, 1.0/1.0 mg/L)是体外活性最好的抗生素。根据BrCAST标准(范围68.7%至74.5%),大约70%的亚胺培南、头孢吡肟、头孢他啶和哌拉西林-他唑巴坦检测菌株被归类为易感,暴露量增加。对头孢唑烷-他唑巴坦的敏感性为84.3% (MIC50/90, 1.0/32.0 mg/L),但仅在949/1239株菌株中进行了评估。对153株菌株进行抗性基因筛选,其中17株(11%)产生blaKPC-2(4株也共同产生blaGES-1)。中的beta-lactamases 22(18%)的123 ceftazidime-avibactam耐药铜绿假单胞菌分离株是:ndm - 1 (n = 5),KPC-2 (n = 5),VIM-2 (n = 5),SPM-1 (n = 1),SPM-1 + GES-1 (n = 1),IMP-16 (n = 1),IMP-56 (n = 1),KPC-2 + GES-1 (n = 1),ndm - 1 + VEB-9 (n = 1),和ndm - 1 + VEB-14 (n = 1)。结论头孢他啶-阿维巴坦和头孢洛赞-他唑巴坦对铜绿假单胞菌临床分离株均具有良好的体外抑制活性(80%)。尽管在研究的分离株中碳青霉烯酶的存在相对较低,但头孢他啶-阿维巴坦的效力(MIC90)是头孢唑嗪-他唑巴坦的5倍,部分原因可能是在评估的分离株中发现了这些β -内酰胺酶。
{"title":"ANALYSIS OF IN VITRO ACTIVITY OF CEFTAZIDIME-AVIBACTAM AGAINST CLINICAL ISOLATES OF PSEUDOMONAS AERUGINOSA COLLECTED FROM BRAZILIAN CENTERS FOR THE ATLAS SURVEILLANCE PROGRAM, 2018-2023","authors":"Lorena Cristina Correa Fehlberg,&nbsp;Camilla Natal De Gaspari,&nbsp;Daniela V Pachito","doi":"10.1016/j.bjid.2026.104629","DOIUrl":"10.1016/j.bjid.2026.104629","url":null,"abstract":"<div><h3>Introduction</h3><div><em>Pseudomonas aeruginosa</em> is a pathogen that causes severe infections that are difficult to treat, as this bacterium can express multiple resistance mechanisms, in addition to its intrinsically limited susceptibility to many antibiotics. In this study, the <em>in vitro</em> activity of ceftazidime-avibactam was evaluated against clinical isolates of <em>P. aeruginosa</em>, both carbapenemase-producing and non-producing, collected as part of the global ATLAS surveillance program.</div></div><div><h3>Methods</h3><div>A total of 1239 non-duplicate <em>P. aeruginosa</em> isolates were evaluated, collected from different infection sites in hospitals across Brazil between 2018 and 2023. Susceptibility testing was performed using broth microdilution. The antimicrobial susceptibility profile was analyzed according to the breakpoints established by BrCAST (2025). The search for carbapenemase-encoding genes was performed by PCR followed by sequencing. Results Ceftazidime-avibactam (90.0% susceptible; MIC50/90, 2.0/8.0 mg/L) and colistin (99.8% susceptible; MIC50/90, 1.0/1.0 mg/L) were the antibiotics with the best <em>in vitro</em> activity. Approximately 70% of isolates tested for imipenem, cefepime, ceftazidime, and piperacillin-tazobactam were classified as susceptible with increased exposure, according to BrCAST criteria (range 68.7% to 74.5%). Susceptibility to ceftolozane-tazobactam was 84.3% (MIC50/90, 1.0/32.0 mg/L), but this antibiotic was evaluated in only 949/1239 isolates. Resistance gene screening was performed on 153 isolates, of which 17 (11%) were blaKPC-2 producers (4 also coproduced blaGES-1). The beta-lactamases found in 22 (18%) of the 123 ceftazidime-avibactam resistant <em>P. aeruginosa</em> isolates were: NDM-1 (n = 5), KPC-2 (n = 5), VIM-2 (n = 5), SPM-1 (n = 1), SPM-1+GES-1 (n = 1), IMP-16 (n = 1), IMP-56 (n = 1), KPC-2+GES-1 (n = 1), NDM-1+VEB-9 (n = 1), and NDM-1+VEB-14 (n = 1).</div></div><div><h3>Conclusion</h3><div>The results demonstrated that both ceftazidime-avibactam and ceftolozane-tazobactam maintain excellent <em>in vitro</em> activity (&gt; 80%) against clinical isolates of <em>P. aeruginosa</em>. Although the presence of carbapenemases was relatively low among the isolates studied, ceftazidime-avibactam was 5 times more potent (MIC90) compared to ceftolozane-tazobactam, which may be partly explained by the presence of these beta-lactamases identified in the evaluated isolates.</div></div>","PeriodicalId":56327,"journal":{"name":"Brazilian Journal of Infectious Diseases","volume":"30 ","pages":"Article 104629"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454192","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
ANALYSIS OF PHARMACEUTICAL INTERVENTIONS IN ANTIMICROBIALS AFTER IMPLEMENTATION OF A CLINICAL PHARMACIST SPECIALIZED IN THE ANTIMICROBIAL STEWARDSHIP PROGRAM 临床药师在抗菌药物管理项目实施后的药物干预分析
IF 2.8 4区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2026-03-01 Epub Date: 2026-03-14 DOI: 10.1016/j.bjid.2026.104630
Tatiana Aporta Marins, Moacyr Silva Junior, Emy Akiyama Gouveia, Maria Daniela Di Dea Bergamasco, Roberta Gonsalez dos Santos, Silvana Maria de Almeida

Introduction

Inappropriate use of antimicrobials is a global challenge and contributes to increased microbial resistance and clinical complications. Effective management of these drugs is essential to optimize treatment and preserve the efficacy of antimicrobials. Antimicrobial Stewardship Programs (ASP) aim to ensure the appropriate use of antimicrobials (ATM) and achieve better clinical and microbiological outcomes, and several studies demonstrate the essential role of the clinical pharmacist in this context. Our objective was to evaluate pharmaceutical interventions in antimicrobials after the implementation of a clinical pharmacist dedicated to the ASP and specialized in infectious diseases.

Methods

A retrospective and quantitative analysis of pharmaceutical interventions in antimicrobials was conducted in the years 2023, 2024, and the first quarter of 2025. Data were collected monthly, recording the reasons for interventions, total number and monthly average of interventions, and the adherence rate of medical teams.

Results

Among the three main reasons for pharmacotherapeutic interventions were duration of therapy, dose, and indication. In 2023, 3,353 interventions were recorded, with a monthly average of 279 and an adherence rate of 74.7%. In 2024, the total number of interventions increased to 4,298, with a monthly average of 358 and an adherence rate of 81.1%. In the first quarter of 2025, 1,389 interventions were performed, resulting in a monthly average of 463 and an adherence rate of 88.3%. These data demonstrate an increase over time in both the number of monthly interventions and the adherence of medical teams.

Conclusion

The implementation of a specialist clinical pharmacist dedicated to antimicrobial management resulted in a substantial increase in pharmacotherapeutic interventions and in the adherence of medical teams. These results indicate that the presence of a professional specialized in the Antimicrobial Stewardship Program is essential to improve clinical practice and promote the appropriate use of antimicrobials, contributing to the fight against microbial resistance. Continuity and expansion of this model are recommended to further optimize clinical outcomes and patient safety.
不适当使用抗菌素是一项全球性挑战,并导致微生物耐药性增加和临床并发症。有效管理这些药物对于优化治疗和保持抗微生物药物的疗效至关重要。抗菌药物管理计划(ASP)旨在确保抗菌药物(ATM)的适当使用,并取得更好的临床和微生物学结果,一些研究表明临床药师在这方面的重要作用。我们的目标是评估在实施一名专门从事ASP和传染病的临床药剂师后,抗菌剂的药物干预措施。方法对2023年、2024年和2025年第一季度抗菌素药物干预进行回顾性和定量分析。每月收集数据,记录干预的原因、干预的总数和月平均值以及医疗队的依从率。结果药物治疗干预的三个主要原因是治疗时间、剂量和适应证。2023年,记录了3353项干预措施,平均每月279项,依从率为74.7%。2024年,干预总次数增加到4298次,月平均358次,依从率为81.1%。在2025年第一季度,进行了1,389次干预,平均每月463次,依从率为88.3%。这些数据表明,随着时间的推移,每月干预的次数和医疗小组的依从性都有所增加。结论临床专科药师专职抗菌药物管理的实施,使药物治疗干预措施和医疗团队的依从性显著提高。这些结果表明,抗菌药物管理计划中专业人员的存在对于改善临床实践和促进抗菌药物的适当使用至关重要,有助于对抗微生物耐药性。建议继续和扩展该模型,以进一步优化临床结果和患者安全。
{"title":"ANALYSIS OF PHARMACEUTICAL INTERVENTIONS IN ANTIMICROBIALS AFTER IMPLEMENTATION OF A CLINICAL PHARMACIST SPECIALIZED IN THE ANTIMICROBIAL STEWARDSHIP PROGRAM","authors":"Tatiana Aporta Marins,&nbsp;Moacyr Silva Junior,&nbsp;Emy Akiyama Gouveia,&nbsp;Maria Daniela Di Dea Bergamasco,&nbsp;Roberta Gonsalez dos Santos,&nbsp;Silvana Maria de Almeida","doi":"10.1016/j.bjid.2026.104630","DOIUrl":"10.1016/j.bjid.2026.104630","url":null,"abstract":"<div><h3>Introduction</h3><div>Inappropriate use of antimicrobials is a global challenge and contributes to increased microbial resistance and clinical complications. Effective management of these drugs is essential to optimize treatment and preserve the efficacy of antimicrobials. Antimicrobial Stewardship Programs (ASP) aim to ensure the appropriate use of antimicrobials (ATM) and achieve better clinical and microbiological outcomes, and several studies demonstrate the essential role of the clinical pharmacist in this context. Our objective was to evaluate pharmaceutical interventions in antimicrobials after the implementation of a clinical pharmacist dedicated to the ASP and specialized in infectious diseases.</div></div><div><h3>Methods</h3><div>A retrospective and quantitative analysis of pharmaceutical interventions in antimicrobials was conducted in the years 2023, 2024, and the first quarter of 2025. Data were collected monthly, recording the reasons for interventions, total number and monthly average of interventions, and the adherence rate of medical teams.</div></div><div><h3>Results</h3><div>Among the three main reasons for pharmacotherapeutic interventions were duration of therapy, dose, and indication. In 2023, 3,353 interventions were recorded, with a monthly average of 279 and an adherence rate of 74.7%. In 2024, the total number of interventions increased to 4,298, with a monthly average of 358 and an adherence rate of 81.1%. In the first quarter of 2025, 1,389 interventions were performed, resulting in a monthly average of 463 and an adherence rate of 88.3%. These data demonstrate an increase over time in both the number of monthly interventions and the adherence of medical teams.</div></div><div><h3>Conclusion</h3><div>The implementation of a specialist clinical pharmacist dedicated to antimicrobial management resulted in a substantial increase in pharmacotherapeutic interventions and in the adherence of medical teams. These results indicate that the presence of a professional specialized in the Antimicrobial Stewardship Program is essential to improve clinical practice and promote the appropriate use of antimicrobials, contributing to the fight against microbial resistance. Continuity and expansion of this model are recommended to further optimize clinical outcomes and patient safety.</div></div>","PeriodicalId":56327,"journal":{"name":"Brazilian Journal of Infectious Diseases","volume":"30 ","pages":"Article 104630"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454193","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
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Brazilian Journal of Infectious Diseases
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