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Clinical and molecular characteristics of KPC-producing Klebsiella pneumoniae bloodstream infections: Results of a multicentre study
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-24 DOI: 10.1016/j.jgar.2025.01.009
Lucia Brescini , Gloria D'Achille , Chiara Papalini , Francesco Pallotta , Lucia Teodori , Donatella Pietrella , Antonella Mencacci , Benedetta Canovari , Barbara Pieretti , Marina Mingoia , Roberto Montalti , Gianluca Morroni , Maria Bruna Pasticci , Francesco Barchiesi

Objective

Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) is a great cause of concern and often associated with bloodstream infections (BSIs) and a high mortality rate. Here we identified the risk factors of KPC-Kp BSIs observed in three Italian hospitals and studied the epidemiology of KPC-Kp strains.

Methods

A retrospective analysis of KPC-Kp BSIs was performed from 2014 to 2019 at three hospitals in central Italy (Ancona, Pesaro-Fano, and Perugia). Uni- and multi-variable analyses were performed to evaluate the clinical variables associated with mortality. Pulsed-field gel electrophoresis assay and whole-genome sequencing analysis of KPC-Kp isolates was carried out to identify antibiotic resistance genes and epidemiological relationships among the strains.

Results

A total of 219 patients were considered. Mortality on day 30 was 32%, with older age, APACHE II score ≥11, Charlson Comorbidity Index ≥4, and solid tumours more frequent in patients with a negative outcome. Positive outcomes were related to combination therapy with at least two active drugs that also emerged in multivariate analysis. Most KPC-Kp strains belonged to three major sequence types (ST512, ST307, and ST101), while the most common carbapenem resistance gene variant was blaKPC-3.

Conclusions

KPC-Kp BSIs remain a challenging infection with a high crude mortality rate. Patient conditions and comorbidities correlate with negative outcomes, while active drugs are correlated with better outcomes. Although collected from different hospitals, the KPC-Kp strains were epidemiologically related, suggesting inter-hospital diffusion. Timely and effective therapy, together with epidemiological surveillance, are crucial to reduce mortality and prevent the spread of nosocomial clones.
{"title":"Clinical and molecular characteristics of KPC-producing Klebsiella pneumoniae bloodstream infections: Results of a multicentre study","authors":"Lucia Brescini ,&nbsp;Gloria D'Achille ,&nbsp;Chiara Papalini ,&nbsp;Francesco Pallotta ,&nbsp;Lucia Teodori ,&nbsp;Donatella Pietrella ,&nbsp;Antonella Mencacci ,&nbsp;Benedetta Canovari ,&nbsp;Barbara Pieretti ,&nbsp;Marina Mingoia ,&nbsp;Roberto Montalti ,&nbsp;Gianluca Morroni ,&nbsp;Maria Bruna Pasticci ,&nbsp;Francesco Barchiesi","doi":"10.1016/j.jgar.2025.01.009","DOIUrl":"10.1016/j.jgar.2025.01.009","url":null,"abstract":"<div><h3>Objective</h3><div><em>Klebsiella pneumoniae</em> carbapenemase-producing <em>K. pneumoniae</em> (KPC-Kp) is a great cause of concern and often associated with bloodstream infections (BSIs) and a high mortality rate. Here we identified the risk factors of KPC-Kp BSIs observed in three Italian hospitals and studied the epidemiology of KPC-Kp strains.</div></div><div><h3>Methods</h3><div>A retrospective analysis of KPC-Kp BSIs was performed from 2014 to 2019 at three hospitals in central Italy (Ancona, Pesaro-Fano, and Perugia). Uni- and multi-variable analyses were performed to evaluate the clinical variables associated with mortality. Pulsed-field gel electrophoresis assay and whole-genome sequencing analysis of KPC-Kp isolates was carried out to identify antibiotic resistance genes and epidemiological relationships among the strains.</div></div><div><h3>Results</h3><div>A total of 219 patients were considered. Mortality on day 30 was 32%, with older age, APACHE II score ≥11, Charlson Comorbidity Index ≥4, and solid tumours more frequent in patients with a negative outcome. Positive outcomes were related to combination therapy with at least two active drugs that also emerged in multivariate analysis. Most KPC-Kp strains belonged to three major sequence types (ST512, ST307, and ST101), while the most common carbapenem resistance gene variant was <em>bla</em><sub>KPC-3</sub>.</div></div><div><h3>Conclusions</h3><div>KPC-Kp BSIs remain a challenging infection with a high crude mortality rate. Patient conditions and comorbidities correlate with negative outcomes, while active drugs are correlated with better outcomes. Although collected from different hospitals, the KPC-Kp strains were epidemiologically related, suggesting inter-hospital diffusion. Timely and effective therapy, together with epidemiological surveillance, are crucial to reduce mortality and prevent the spread of nosocomial clones.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"41 ","pages":"Pages 216-223"},"PeriodicalIF":3.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Antimicrobial susceptibility of gram-negative bacteria: analysis from patients in a laboratory network in Brazil. 革兰氏阴性细菌的抗菌药敏感性:巴西实验室网络中对患者的分析。
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-24 DOI: 10.1016/j.jgar.2025.01.019
Amanda Azevedo Bittencourt, Thales José Polis, Vinicius Lima Faustino, Paula de Mendonça Batista, Ana Carolina Padula Ribeiro Pereira, Marina Della Negra de Paula, Darlan Augusto da Costa Rocha, Paola Cappellano Daher, Jorge Luiz Mello Sampaio

Objectives: This study aimed to describe the epidemiology and antimicrobial susceptibility patterns of gram-negative pathogens in Brazil from 2018 to 2020, addressing the gap in national data on healthcare-associated infections, using information from a private laboratory network.

Methods: A cross-sectional study was conducted using a database from Fleury hospital network, a private laboratory in Brazil. The analysis included blood, urine, and lower respiratory tract samples collected from January 2018 to June 2020. The study included consecutive non-duplicated isolates of Enterobacterales or P. aeruginosa from inpatients aged ≥18 years old. Bacterial identification was performed using mass spectrometry, and antimicrobial susceptibility was determined following EUCAST/BrCAST guidelines.

Results: A total of 25,180 isolates were included in the analysis. Most of the sample consisted of female patients (57.9%), with a mean age of 70 years (SD 18.1). Enterobacterales were the most prevalent pathogens found (76.2%), while P. aeruginosa was present in the remaining 23.8%. In terms of antimicrobial susceptibility, Enterobacterales exhibited a higher susceptibility rate to ceftazidime/avibactam (97.1%) and amikacin (95.6%), while P. aeruginosa showed a higher susceptibility rate to polymyxin B (97.1%) and ceftolozane/tazobactam (86.6%). Among carbapenem-resistant P. aeruginosa isolates, 75% were susceptible to ceftolozane/tazobactam. Additionally, 24.2% of K. pneumoniae complex samples were identified.

Conclusion: Enterobacterales was the most frequently encountered group in Brazil. Ceftazidime/avibactam and amikacin demonstrated the highest efficacy against this group, while ceftolozane/tazobactam and polymyxin had the highest efficacy against P. aeruginosa. This highlights the importance of new β-lactam-β-lactamase inhibitor combinations for the treatment of gram-negative infections.

{"title":"Antimicrobial susceptibility of gram-negative bacteria: analysis from patients in a laboratory network in Brazil.","authors":"Amanda Azevedo Bittencourt, Thales José Polis, Vinicius Lima Faustino, Paula de Mendonça Batista, Ana Carolina Padula Ribeiro Pereira, Marina Della Negra de Paula, Darlan Augusto da Costa Rocha, Paola Cappellano Daher, Jorge Luiz Mello Sampaio","doi":"10.1016/j.jgar.2025.01.019","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.01.019","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to describe the epidemiology and antimicrobial susceptibility patterns of gram-negative pathogens in Brazil from 2018 to 2020, addressing the gap in national data on healthcare-associated infections, using information from a private laboratory network.</p><p><strong>Methods: </strong>A cross-sectional study was conducted using a database from Fleury hospital network, a private laboratory in Brazil. The analysis included blood, urine, and lower respiratory tract samples collected from January 2018 to June 2020. The study included consecutive non-duplicated isolates of Enterobacterales or P. aeruginosa from inpatients aged ≥18 years old. Bacterial identification was performed using mass spectrometry, and antimicrobial susceptibility was determined following EUCAST/BrCAST guidelines.</p><p><strong>Results: </strong>A total of 25,180 isolates were included in the analysis. Most of the sample consisted of female patients (57.9%), with a mean age of 70 years (SD 18.1). Enterobacterales were the most prevalent pathogens found (76.2%), while P. aeruginosa was present in the remaining 23.8%. In terms of antimicrobial susceptibility, Enterobacterales exhibited a higher susceptibility rate to ceftazidime/avibactam (97.1%) and amikacin (95.6%), while P. aeruginosa showed a higher susceptibility rate to polymyxin B (97.1%) and ceftolozane/tazobactam (86.6%). Among carbapenem-resistant P. aeruginosa isolates, 75% were susceptible to ceftolozane/tazobactam. Additionally, 24.2% of K. pneumoniae complex samples were identified.</p><p><strong>Conclusion: </strong>Enterobacterales was the most frequently encountered group in Brazil. Ceftazidime/avibactam and amikacin demonstrated the highest efficacy against this group, while ceftolozane/tazobactam and polymyxin had the highest efficacy against P. aeruginosa. This highlights the importance of new β-lactam-β-lactamase inhibitor combinations for the treatment of gram-negative infections.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Fatal septicemia caused by Francisella philomiragia in an immunocompetent patient.
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-23 DOI: 10.1016/j.jgar.2025.01.005
Junghyeon Yun, Kyung-Wook Hong, Jung-Hyun Byun
{"title":"Fatal septicemia caused by Francisella philomiragia in an immunocompetent patient.","authors":"Junghyeon Yun, Kyung-Wook Hong, Jung-Hyun Byun","doi":"10.1016/j.jgar.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.01.005","url":null,"abstract":"","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Mechanisms of blaIMP-4 dissemination across diverse carbapenem-resistant clinical isolates blaIMP-4在不同碳青霉烯耐药临床分离株间传播的机制
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-16 DOI: 10.1016/j.jgar.2025.01.003
Ying Fu , Faye C. Morris , Stephanie C. Pereira , Xenia Kostoulias , Yan Jiang , Callum Vidor , Galain Williams , Yogi Srikhanta , Nenad Macesic , Yunsong Yu , Dena Lyras , Anton Y. Peleg

Objective

The IMP-4 carbapenemase is an endemic cause of carbapenem resistance in the Asia-Pacific region. Our aim was to determine the dissemination mechanism of the blaIMP-4 gene.

Methods

Twelve representative Australian IMP-4 clinical isolates from The Alfred Hospital (Victoria, Australia) were characterised using antimicrobial susceptibility testing, with their genome and plasmid assemblies analysed. The conjugation efficiencies of different plasmids were investigated using filter mating with four recipient strains across two species.

Results

Selected IMP-4 isolates included six species and four genera (Enterobacter, Klebsiella, Serratia, and Acinetobacter), whereby isolates of the same species belonged to the same sequence type and were closely related. Four IMP-4 plasmid types were noted: IncHI2A types 1 and 2 (Klebsiella spp. and Enterobacter hormaechei, respectively), IncC (Serratia marcescens and Klebsiella pneumoniae), and a novel type in Acinetobacter pittii. Sequence homology was observed across all plasmids at the blaIMP-4 location, termed Region I, with IS26 on IncHI2A, and IS5075 and Tn3 resistance gene cassettes present on IncC plasmids. Genomic rearrangements mediated by IS26 or Tn3 and IS5075 were identified in Region I of plasmids from the same Inc type. The plasmids of each Inc type were capable of conjugative transfer with varying efficiency. IncH12A plasmids and K. pneumoniae IncC displayed higher transfer efficiencies than other plasmids examined in this study when using the recipient E. coli strain J53 (with conjugation efficiencies of 1.17×10−2 to 5.02×10−5, P < 0.001).

Conclusions

Clonal spread, Inc type, homologous region, and insertion sequences are important mobility factors in the dissemination and evolution of blaIMP-4 plasmids.
目的:IMP-4碳青霉烯酶是亚太地区碳青霉烯耐药的一种地方性原因。我们的目的是确定blaIMP-4基因的传播机制。方法:对阿尔弗雷德医院12株具有代表性的澳大利亚IMP-4临床分离株进行药敏试验和基因组和质粒组装分析。采用过滤交配的方法,研究了不同质粒与两种不同受体菌株的结合效率。结果:所选IMP-4分离株包括Enterobacter、Klebsiella、Serratia和Acinetobacter 4属6种,其中同一种分离株属于同一序列型,亲缘关系密切。发现了4种IMP-4质粒类型:IncHI2A 1型和2型(分别为克雷伯氏菌和霍氏肠杆菌),IncC(粘质沙雷氏菌和肺炎克雷伯氏菌),以及pittii不动杆菌中的一种新型质粒。在blaIMP-4位点(称为I区)的所有质粒中观察到序列同源性,IncHI2A和is5075和Tn3抗性基因磁带上的IS26-分别存在于IncC质粒上。在同一Inc型的质粒I区发现了由IS26或Tn3和IS5075介导的基因组重排。每种Inc类型的质粒都能以不同的效率进行共轭转移。IncH12A质粒和肺炎克雷伯菌IncC在使用受体大肠杆菌J53时表现出较高的转移效率(结合效率为1.17×10-2 - 5.02×10-5, p)。结论:克隆传播、Inc型、同源区和插入序列是blaIMP-4质粒传播和进化的重要迁移因素。
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引用次数: 0
Genomic insights into a multidrug-resistant pandoraea apista clinical isolate carrying blaOXA-153 from China 中国携带blaOXA-153的多药耐药apista临床分离株的基因组分析
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-15 DOI: 10.1016/j.jgar.2025.01.002
Lirong Li , Yawen Zhang , Fang He , Ningjun wu

Objectives

Pandoraea apista is notable for its multidrug resistance and is frequently identified in patients with cystic fibrosis or other chronic lung diseases, where it contributes to persistent lung infections. In this study, we describe a strain of P. apista harboring the blaOXA-153, isolated from the bronchoalveolar lavage (BAL) fluid of an inpatient in China.

Methods

The genomic DNA of P. apista strain PA167 was sequenced using the Illumina NovaSeq 6000 system and assembled with SPAdes v.3.13.0. Antimicrobial resistance genes (ARGs) were identified using ResFinder v.3.2 within the ABRicate v.0.9.0. Phylogenetic analysis was performed using the Snippy v.4.6.0.

Results

The genome sequence of P. apista strain PA167 comprises 5,580,873 bp, with 4,926 protein-coding sequences, 4 ncRNAs, 59 tRNAs, and 3 rRNA operons. Only one ARG was identified: blaOXA-153. PA167 exhibited resistance to multiple antibiotics, including cephalosporins and carbapenems, and was susceptible only to sulfamethoxazole/trimethoprim. Twenty-four P. apista strains, including PA167, could be retrieved from the NCBI database, all carrying the blaOXA-153. Complete genomic sequencing of five strains confirmed the chromosomal presence of blaOXA-153. The isolation sources of these 24 strains were predominantly clinical samples, mainly respiratory specimens, with some strains isolated from environmental sources.

Conclusion

Here, we present the genome sequence of a P. apista strain carrying the blaOXA-153, marking the first isolation of this strain from a clinical setting in China. The potential for future epidemic spread highlights the necessity for targeted antimicrobial strategies.
目的:apista潘多拉菌以其多药耐药而闻名,经常在囊性纤维化或其他慢性肺部疾病患者中发现,在这些患者中,它会导致持续性肺部感染。在这项研究中,我们描述了从中国住院患者的支气管肺泡灌洗液(BAL)中分离出的携带blaOXA-153的apista菌株。方法:采用Illumina NovaSeq 6000系统对P. apista菌株PA167基因组DNA进行测序,并用SPAdes v.3.13.0软件进行组装。抗菌药物耐药基因(ARGs)在ABRicate v.0.9.0中使用ResFinder v.3.2进行鉴定。使用Snippy v.4.6.0进行系统发育分析。结果:apista菌株PA167基因组序列为5,580,873 bp,包含4,926个蛋白编码序列,4个ncrna, 59个trna和3个rRNA操作子。仅鉴定出一种ARG: blaOXA-153。PA167对包括头孢菌素和碳青霉烯类在内的多种抗生素耐药,仅对磺胺甲恶唑/甲氧苄啶敏感。从NCBI数据库中检索到24株apista菌株,包括PA167,均携带blaOXA-153。5株菌株的全基因组测序证实了blaOXA-153在染色体上的存在。24株分离源以临床标本为主,以呼吸道标本为主,部分分离源为环境源。结论:在这里,我们提出了携带blaOXA-153的apista菌株的基因组序列,这标志着该菌株首次从中国临床环境中分离出来。未来流行病传播的可能性突出了有针对性的抗微生物战略的必要性。
{"title":"Genomic insights into a multidrug-resistant pandoraea apista clinical isolate carrying blaOXA-153 from China","authors":"Lirong Li ,&nbsp;Yawen Zhang ,&nbsp;Fang He ,&nbsp;Ningjun wu","doi":"10.1016/j.jgar.2025.01.002","DOIUrl":"10.1016/j.jgar.2025.01.002","url":null,"abstract":"<div><h3>Objectives</h3><div><em>Pandoraea apista</em> is notable for its multidrug resistance and is frequently identified in patients with cystic fibrosis or other chronic lung diseases, where it contributes to persistent lung infections. In this study, we describe a strain of <em>P. apista</em> harboring the <em>bla</em><sub>OXA-153</sub>, isolated from the bronchoalveolar lavage (BAL) fluid of an inpatient in China.</div></div><div><h3>Methods</h3><div>The genomic DNA of <em>P. apista</em> strain PA167 was sequenced using the Illumina NovaSeq 6000 system and assembled with SPAdes v.3.13.0. Antimicrobial resistance genes (ARGs) were identified using ResFinder v.3.2 within the ABRicate v.0.9.0. Phylogenetic analysis was performed using the Snippy v.4.6.0.</div></div><div><h3>Results</h3><div>The genome sequence of <em>P. apista</em> strain PA167 comprises 5,580,873 bp, with 4,926 protein-coding sequences, 4 ncRNAs, 59 tRNAs, and 3 rRNA operons. Only one ARG was identified: <em>bla</em><sub>OXA-153</sub>. PA167 exhibited resistance to multiple antibiotics, including cephalosporins and carbapenems, and was susceptible only to sulfamethoxazole/trimethoprim. Twenty-four <em>P. apista</em> strains, including PA167, could be retrieved from the NCBI database, all carrying the <em>bla</em><sub>OXA-153</sub>. Complete genomic sequencing of five strains confirmed the chromosomal presence of <em>bla</em><sub>OXA-153</sub>. The isolation sources of these 24 strains were predominantly clinical samples, mainly respiratory specimens, with some strains isolated from environmental sources.</div></div><div><h3>Conclusion</h3><div>Here, we present the genome sequence of a <em>P. apista</em> strain carrying the <em>bla</em><sub>OXA-153</sub>, marking the first isolation of this strain from a clinical setting in China. The potential for future epidemic spread highlights the necessity for targeted antimicrobial strategies.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"41 ","pages":"Pages 159-161"},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Antimicrobial susceptibility and epidemiological types of Legionella pneumophila human isolates from Italy (1987–2020) 意大利嗜肺军团菌人分离株的抗菌药物敏感性和流行病学类型(1987-2020)
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-15 DOI: 10.1016/j.jgar.2024.12.030
Maria Scaturro , Alessio Lanni , Fabiola Mancini , Antonietta Girolamo , Silvia Fillo , Andrea Ciammaruconi , Florigio Lista , Clementina Elvezia Cocuzza , Rosario Musumeci , Christophe Ginevra , Ghislaine Descours , Sophie Jarraud , Jessica Iera , Paolo Visca , Maria Luisa Ricci

Objectives

Although antimicrobial resistance has not yet emerged as an overarching problem for Legionella pneumophila (L. pneumophila) infection, the description of clinical and environmental strains resistant to fluoroquinolones and macrolides is a cause of concern. This study aimed to investigate the antimicrobial susceptibility of L. pneumophila human isolates in Italy.

Methods

A total of 204 L. pneumophila clinical isolates were tested for sensitivity to 9 antibiotics using the broth microdilution assay (BMD). All isolates were typed by sequence-based typing, and Legionella pneumophila serogroup 1 (Lp1) isolates by monoclonal antibody subgrouping. Minimum inhibitory concentration (MIC) data were correlated with the possible source of infection and geographical distribution. The presence of the lpeAB efflux pump genes was also investigated. The genome sequences of a subpopulation of isolates showing reduced susceptibility to azithromycin were also analysed.

Results

The L. pneumophila isolates did not show significant resistance to the tested antibiotics, although a trend toward reduced sensitivity to azithromycin was observed in a subpopulation of 46 strains, most of which belonged to sequence type 1 (ST1), the second most widespread ST in Italy. An amplicon of the expected size overlapping the lpeAB genes was obtained only in the 46-subpopulation above mentioned. In 4 of the 46 isolates, sequencing analysis showed the occurrence of amino-acid substitutions already described in other strains. No further mutation was found.

Conclusions

The presence of L. pneumophila strains with reduced susceptibility or resistance to azithromycin should be monitored to predict future trends and suggest to physicians a combined therapy with fluoroquinolones when a poor response to azithromycin is observed. © 2025 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.
背景:虽然抗菌药物耐药性尚未成为嗜肺军团菌(Lp)感染的首要问题,但对氟喹诺酮类药物和大环内酯类药物耐药的临床和环境菌株的描述是一个令人关注的问题。本研究旨在调查意大利Lp人分离株的抗菌药物敏感性。方法:采用微量肉汤稀释法(BMD)检测204株Lp临床分离株对9种抗生素的敏感性。所有分离株均采用序列分型,嗜肺军团菌血清1组(Lp1)分离株采用单克隆抗体亚群分型。最低抑菌浓度数据与可能的感染源和地理分布相关。我们还研究了lpeAB外排泵基因的存在。还分析了对阿奇霉素敏感性降低的分离物亚群的基因组序列。结果:Lp分离株对所测试的抗生素没有表现出明显的耐药性,尽管在46株菌株的亚群中观察到对阿奇霉素敏感性降低的趋势,其中大多数属于序列1型(ST1),这是意大利第二大分布的ST。仅在上述46个亚群中获得了与lpeAB基因重叠的预期大小的扩增子。在46株分离株中,有4株测序分析显示发生了在其他菌株中已经描述过的氨基酸替换。没有发现进一步的突变。结论:应监测对阿奇霉素敏感性或耐药性降低的Lp菌株的存在,以预测未来趋势,并在观察到阿奇霉素不良反应时向医生建议氟喹诺酮类药物联合治疗。
{"title":"Antimicrobial susceptibility and epidemiological types of Legionella pneumophila human isolates from Italy (1987–2020)","authors":"Maria Scaturro ,&nbsp;Alessio Lanni ,&nbsp;Fabiola Mancini ,&nbsp;Antonietta Girolamo ,&nbsp;Silvia Fillo ,&nbsp;Andrea Ciammaruconi ,&nbsp;Florigio Lista ,&nbsp;Clementina Elvezia Cocuzza ,&nbsp;Rosario Musumeci ,&nbsp;Christophe Ginevra ,&nbsp;Ghislaine Descours ,&nbsp;Sophie Jarraud ,&nbsp;Jessica Iera ,&nbsp;Paolo Visca ,&nbsp;Maria Luisa Ricci","doi":"10.1016/j.jgar.2024.12.030","DOIUrl":"10.1016/j.jgar.2024.12.030","url":null,"abstract":"<div><h3>Objectives</h3><div>Although antimicrobial resistance has not yet emerged as an overarching problem for <em>Legionella pneumophila</em> (<em>L. pneumophila</em>) infection, the description of clinical and environmental strains resistant to fluoroquinolones and macrolides is a cause of concern. This study aimed to investigate the antimicrobial susceptibility of <em>L. pneumophila</em> human isolates in Italy.</div></div><div><h3>Methods</h3><div>A total of 204 <em>L. pneumophila</em> clinical isolates were tested for sensitivity to 9 antibiotics using the broth microdilution assay (BMD). All isolates were typed by sequence-based typing, and <em>Legionella pneumophila</em> serogroup 1 (Lp1) isolates by monoclonal antibody subgrouping. Minimum inhibitory concentration (MIC) data were correlated with the possible source of infection and geographical distribution. The presence of the <em>lpeAB</em> efflux pump genes was also investigated. The genome sequences of a subpopulation of isolates showing reduced susceptibility to azithromycin were also analysed.</div></div><div><h3>Results</h3><div>The <em>L. pneumophila</em> isolates did not show significant resistance to the tested antibiotics, although a trend toward reduced sensitivity to azithromycin was observed in a subpopulation of 46 strains, most of which belonged to sequence type 1 (ST1), the second most widespread ST in Italy. An amplicon of the expected size overlapping the <em>lpeAB</em> genes was obtained only in the 46-subpopulation above mentioned. In 4 of the 46 isolates, sequencing analysis showed the occurrence of amino-acid substitutions already described in other strains. No further mutation was found<em>.</em></div></div><div><h3>Conclusions</h3><div>The presence of <em>L. pneumophila</em> strains with reduced susceptibility or resistance to azithromycin should be monitored to predict future trends and suggest to physicians a combined therapy with fluoroquinolones when a poor response to azithromycin is observed. © 2025 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"41 ","pages":"Pages 181-188"},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Drug-resistant tuberculosis is an important challenge in long COVID patients 耐药结核病是长期COVID患者面临的重要挑战。
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-14 DOI: 10.1016/j.jgar.2024.12.027
Masoud Mohammadi , Seyed Hassan Faghihi
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引用次数: 0
Impact of meropenem exposure on fluoroquinolone and carbapenem resistance in Pseudomonas aeruginosa infection in inpatients in a Japanese university hospital: Insights into oprD mutations and efflux pump overexpression 美罗培南暴露对日本某大学医院住院患者铜绿假单胞菌感染中氟喹诺酮和碳青霉烯类耐药的影响:oprD突变和外排泵过表达的见解
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-14 DOI: 10.1016/j.jgar.2024.12.029
Tadanori Yamochi , Kazuhisa Ugajin , Rintaro On , Sho Inoue , Hiromi Ikeda , Toshiko Yamochi , Masafumi Takimoto , Issei Tokimatsu

Objectives

In Pseudomonas aeruginosa isolates, emerging meropenem resistance beyond imipenem resistance has become a problem. In this study, we aimed to investigate the relationship between the in vivo acquisition of antimicrobial resistance in fluoroquinolone- and carbapenem-resistant P. aeruginosa clinical isolates, the underlying molecular mechanisms, and exposure to antimicrobial agents.

Methods

Pulsed-field gel electrophoreses were performed to study the molecular relatedness of nine clinical isolates from a Japanese hospital. The minimal inhibitory concentrations of clinically relevant antibiotics were determined. Quantitative PCR was performed to analyze oprD, mexB, mexC, mexE, and mexY expression. DNA sequencing was performed to identify mutations.

Results

Eight of nine strains were metallo-β-lactamase (MBL) negative, and one strain was MBL positive. All eight non-MBL-resistant strains harbored mutations in the quinoline-resistance-determining regions (QRDR) of gyrA, gyrB, or parC. Five of the eight non-MBL strains had T83I, two had D87N, and one had both T83I and D87N mutations in gyrA. Of these eight strains, three carrying gyrA mutations had another QRDR mutation in subunits, gyrB or parC, associated with mexY overexpression. Additionally, seven of eight dual fluoroquinolone and carbapenem-resistant isolates carried a premature termination codon within oprD, containing either F170L or L7 shortening.

Conclusions

In dual fluoroquinolone- and carbapenem-resistant P. aeruginosa, alterations in the OprD porin and the presence of an active EP are primary resistance mechanisms. Meropenem exposure within the past 59 days may have contributed to the selection of the oprD mutant overexpressing mexB, and meropenem exposure within the past 6 months may have contributed to meropenem resistance.
目的:在铜绿假单胞菌分离株中,除亚胺培南耐药外,新出现的美罗培南耐药已成为一个问题。在本研究中,我们旨在探讨氟喹诺酮类和碳青霉烯类耐药铜绿假单胞菌临床分离株体内获得耐药性的关系、潜在的分子机制以及暴露于抗菌药物之间的关系。方法:采用脉冲场凝胶电泳技术对日本某医院9株临床分离株进行分子亲缘性研究。测定临床相关抗生素的最低抑菌浓度。采用定量PCR检测oprD、mexB、mexC、mexE和mexY的表达。进行DNA测序以鉴定突变。结果:9株菌株中8株为金属β-内酰胺酶(MBL)阴性,1株为MBL阳性。所有8株非mbl耐药菌株都在gyrA、gyrB或ParC的喹啉耐药决定区(QRDR)发生突变。8株非mbl菌株中有5株存在T83I突变,2株存在D87N突变,1株同时存在T83I和D87N突变。在这8个菌株中,3个携带gyrA突变的菌株在与mexY过表达相关的亚基gyrB或parC中有另一个QRDR突变。此外,8株双氟喹诺酮和碳青霉烯耐药菌株中有7株在oprD内携带过早终止密码子,包含F170L或L7缩短。结论:在双氟喹诺酮和碳青霉烯耐药的铜绿假单胞菌中,OprD孔蛋白的改变和活性EP的存在是主要的耐药机制。过去59天内的美罗培南暴露可能导致oprD突变体过表达mexB的选择,过去6个月内的美罗培南暴露可能导致美罗培南耐药性。
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引用次数: 0
Reliability of various antimicrobial susceptibility testing methods for piperacillin/tazobactam in challenging Escherichia coli isolates 哌拉西林/他唑巴坦在大肠杆菌中不同药敏试验方法的可靠性
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-14 DOI: 10.1016/j.jgar.2024.12.028
Faruk Demirocak, Diana Langerak, Erlangga Yusuf

Objective

Piperacillin/tazobactam antimicrobial susceptibility testing (AST) against Enterobacterales can be challenging. The aim of this study was to assess the reproducibility of various automated (VITEK 2) and nonautomated AST methods (broth microdilution (BMD), minimum inhibitory concentration (MIC) test strip, and disk diffusion) for piperacillin/tazobactam in ‘challenging’ E. coli isolates.

Methods

We performed 20 repeated ASTs for seven clinical E. coli isolates: Two resistant to piperacillin/tazobactam but susceptible to amoxicillin/clavulanic acid, four isolates with various β-lactamase coding genes (two blaTEM-1, one blaOXA-1, and one with plasmidal blaampC), and one isolate where VITEK 2 initially could not produce MIC measurements for piperacillin/tazobactam (i.e. no results generated).

Results

Upon repetition, the same MIC as the mode value (i.e. the most frequent MIC value of each AST method) was found between 21% and 87% (BMD), 46% and 100% (VITEK 2), and 48% and 100% (gradient test) of the repetitions. The range of essential agreement percentage (i.e. ±1 doubling dilution from this mode value) was 53–100% (BMD), 63–100% (VITEK 2), and 100% (gradient test). Percent categorical agreement (same susceptible of resistant category using EUCAST breakpoint v. 14.0) was 71–100% (BMD), 85–92% (VITEK 2), 76–100% (gradient test) and 100% (disk diffusion).

Conclusions

: In conclusion, this study provides insight on the reliability of AST results for piperacillin/tazobactam in challenging E. coli isolates. While the results indicate that most methods are generally reproducible, certain isolates may present inconsistent MIC results.
哌拉西林/他唑巴坦抗微生物药敏试验(AST)对肠杆菌具有挑战性。本研究的目的是评估各种自动化(Vitek®2)和非自动化AST方法(肉汤微量稀释(BMD)、最低抑制浓度(MIC)试纸和纸片扩散)在“挑战性”大肠杆菌分离物中检测哌拉西林/他唑巴坦的重复性。我们对7株临床大肠杆菌进行了20次重复AST检测:2株对哌拉西林/他唑巴坦耐药,但对阿莫西林/克拉维酸敏感,4株具有各种β -内酰胺酶编码基因(2株blaTEM-1, 1株blaOXA-1, 1株质粒blaampC), 1株VITEK®2最初无法对哌拉西林/他唑巴坦进行MIC检测(即没有结果)。重复后,发现与模式值相同的MIC值(即每种AST方法的最常见MIC值)在重复的21%至87% (BMD), 46%至100% (VITEK®2)和48%至100%(梯度测试)之间。基本一致性百分比(EA,即从该模式值±1倍稀释)的范围为53%至100% (BMD), 63%至100% (VITEK®2)和100%(梯度测试)。分类一致性百分比(CA,使用EUCAST断点v 14.0的耐药类别相同易感)范围为71%至100% (BMD), 85%至92% (VITEK®2),76%至100%(梯度试验)和100%(磁盘扩散)。综上所述,本研究提供了对哌拉西林/他唑巴坦在挑战大肠杆菌分离株中AST结果的可靠性的见解。虽然结果表明大多数方法通常是可重复的,但某些分离株的MIC结果可能不一致。
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引用次数: 0
Outbreak of carbapenem resistant Klebsiella pneumoniae in a neurorehabilitation unit: Genomic epidemiology reveals complex transmission pattern in a tertiary care hospital 在神经康复病房爆发的耐碳青霉烯肺炎克雷伯菌:基因组流行病学揭示了三级保健医院的复杂传播模式。
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-14 DOI: 10.1016/j.jgar.2025.01.001
Maria Grazia Silvotti , Erika Scaltriti , Luca Bolzoni , Beatrice Zerbi , Gabriella Tocci , Andrea Zappavigna , Gianfranco Lamberti , Federico Donati , Franco Federici , Stefano Pongolini , Giuliana Lo Cascio

Objectives

Infections by carbapenem-resistant Enterobacterales (CRE) in hospitals represent a severe threat but little is known on outbreaks in rehabilitation wards caused by Klebsiella pneumoniae producing Klebsiella pneumoniae Carbapenemase (KPC-Kp). We report an outbreak by KPC-Kp, in a neurorehabilitation unit in Italy, analysed through whole-genome sequencing (WGS) for transmission routes reconstruction to improve management of KPC-Kp infections in rehabilitation units.

Methods

We investigated cases and KPC-Kp isolates collected from February to October 2022 from hospital surveillance. Carbapenem resistance was identified with disk diffusion and minimum inhibitory concentration tests, carbapenemase production through immunochromatographic lateral flow assays. All isolates were genotyped through WGS to highlight possible phylogenetic relationships. The most likely transmission networks of KPC-Kp were reconstructed with Bayesian discrete-time stochastic models.

Results

Nineteen patients were colonized by KPC-Kp. Two isolates belonged to sporadic sequence types (STs; ST348 and ST219) whereas 9 of 19 and 8 of 19 isolates belonged to ST307 and ST716, respectively. Among the ST307 isolates, we identified two genomically distinct clusters of five and two cases. All ST716 isolates were highly similar. Genotyping and the reconstruction of transmission networks of KPC-Kp based on genomic data identified seven independent introductions into the neurorehabilitation unit rather than a single outbreak as initially hypothesized before genomic investigation. Three of the seven introductions generated chains of secondary infections, whereas the remaining four remained single cases.

Conclusions

The outbreak root-causes were identified in temporary staff shortage and insufficient microbiological surveillance. Measures were adopted accordingly and the outbreak ended. The study highlights the critical role of genomic epidemiology in hospital outbreaks. © 2025 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.
目的:医院中碳青霉烯耐药肠杆菌的感染是一种严重的威胁,但对产生肺炎克雷伯菌碳青霉烯酶(KPC-Kp)的肺炎克雷伯菌引起的康复病房暴发知之甚少。我们报告了意大利神经康复病房发生的KPC-Kp暴发,通过全基因组测序(WGS)分析了传播途径重建,以改善康复病房中KPC-Kp感染的管理。方法:对2022年2 - 10月医院监测收集的病例和分离株进行调查。碳青霉烯耐药性鉴定采用圆盘扩散和最小抑制浓度试验,碳青霉烯酶产生采用免疫层析横向流动试验。所有分离株均通过WGS进行基因分型,以突出可能的系统发育关系。用贝叶斯离散时间随机模型重构了KPC-Kp最可能的传输网络。结果:19例患者有KPC-Kp定殖。2株分离株为散发性STs (ST348和ST219), 9/19和8/19分离株分别为ST307和ST716。在ST307分离株中,我们鉴定出两个基因组不同的聚类,分别为5例和2例。所有ST716分离株高度相似。基因分型和基于基因组数据的KPC-Kp传播网络重建确定了神经康复科的7次独立引入,而不是基因组调查前最初假设的一次暴发。七次引入中有三次产生了继发感染链,而其余四次仍然是单个病例。结论:临时人员短缺和微生物监测不足是疫情爆发的根本原因。采取相应措施,疫情结束。该研究强调了基因组流行病学在医院疾病暴发中的关键作用。
{"title":"Outbreak of carbapenem resistant Klebsiella pneumoniae in a neurorehabilitation unit: Genomic epidemiology reveals complex transmission pattern in a tertiary care hospital","authors":"Maria Grazia Silvotti ,&nbsp;Erika Scaltriti ,&nbsp;Luca Bolzoni ,&nbsp;Beatrice Zerbi ,&nbsp;Gabriella Tocci ,&nbsp;Andrea Zappavigna ,&nbsp;Gianfranco Lamberti ,&nbsp;Federico Donati ,&nbsp;Franco Federici ,&nbsp;Stefano Pongolini ,&nbsp;Giuliana Lo Cascio","doi":"10.1016/j.jgar.2025.01.001","DOIUrl":"10.1016/j.jgar.2025.01.001","url":null,"abstract":"<div><h3>Objectives</h3><div>Infections by carbapenem-resistant Enterobacterales (CRE) in hospitals represent a severe threat but little is known on outbreaks in rehabilitation wards caused by <em>Klebsiella pneumoniae</em> producing <em>Klebsiella pneumoniae</em> Carbapenemase (KPC-Kp). We report an outbreak by KPC-Kp, in a neurorehabilitation unit in Italy, analysed through whole-genome sequencing (WGS) for transmission routes reconstruction to improve management of KPC-Kp infections in rehabilitation units.</div></div><div><h3>Methods</h3><div>We investigated cases and KPC-Kp isolates collected from February to October 2022 from hospital surveillance. Carbapenem resistance was identified with disk diffusion and minimum inhibitory concentration tests, carbapenemase production through immunochromatographic lateral flow assays. All isolates were genotyped through WGS to highlight possible phylogenetic relationships. The most likely transmission networks of KPC-Kp were reconstructed with Bayesian discrete-time stochastic models.</div></div><div><h3>Results</h3><div>Nineteen patients were colonized by KPC-Kp. Two isolates belonged to sporadic sequence types (STs; ST348 and ST219) whereas 9 of 19 and 8 of 19 isolates belonged to ST307 and ST716, respectively. Among the ST307 isolates, we identified two genomically distinct clusters of five and two cases. All ST716 isolates were highly similar. Genotyping and the reconstruction of transmission networks of KPC-Kp based on genomic data identified seven independent introductions into the neurorehabilitation unit rather than a single outbreak as initially hypothesized before genomic investigation. Three of the seven introductions generated chains of secondary infections, whereas the remaining four remained single cases.</div></div><div><h3>Conclusions</h3><div>The outbreak root-causes were identified in temporary staff shortage and insufficient microbiological surveillance. Measures were adopted accordingly and the outbreak ended. The study highlights the critical role of genomic epidemiology in hospital outbreaks. © 2025 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"41 ","pages":"Pages 195-201"},"PeriodicalIF":3.7,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Journal of global antimicrobial resistance
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