Pub Date : 2025-04-20DOI: 10.1186/s12941-025-00793-9
Andrew G Ewing, David Joffe, Svetlana Blitshteyn, Anna E S Brooks, Julien Wist, Yaneer Bar-Yam, Stephane Bilodeau, Jennifer Curtin, Rae Duncan, Mark Faghy, Leo Galland, Etheresia Pretorius, Spela Salamon, Danilo Buonsenso, Claire Hastie, Binita Kane, M Asad Khan, Amos Lal, Dennis Lau, Raina MacIntyre, Sammie McFarland, Daniel Munblit, Jeremy Nicholson, Hanna M Ollila, David Putrino, Alberto Rosario, Timothy Tan
Background: Long COVID is a complex, heterogeneous syndrome affecting over four hundred million people globally. There are few recommendations, and no formal training exists for medical professionals to assist with clinical evaluation and management of patients with Long COVID. More research into the pathology, cellular, and molecular mechanisms of Long COVID, and treatments is needed. The goal of this work is to disseminate essential information about Long COVID and recommendations about definition, diagnosis, treatment, research and social issues to physicians, researchers, and policy makers to address this escalating global health crisis.
Methods: A 3-round modified Delphi consensus methodology was distributed internationally to 179 healthcare professionals, researchers, and persons with lived experience of Long COVID in 28 countries. Statements were combined into specific areas: definition, diagnosis, treatment, research, and society.
Results: The survey resulted in 187 comprehensive statements reaching consensus with the strongest areas being diagnosis and clinical assessment, and general research. We establish conditions for diagnosis of different subgroups within the Long COVID umbrella. Clear consensus was reached that the impacts of COVID-19 infection on children should be a research priority, and additionally on the need to determine the effects of Long COVID on societies and economies. The consensus on COVID and Long COVID is that it affects the nervous system and other organs and is not likely to be observed with initial symptoms. We note, biomarkers are critically needed to address these issues.
Conclusions: This work forms initial guidance to address the spectrum of Long COVID as a disease and reinforces the need for translational research and large-scale treatment trials for treatment protocols.
{"title":"Long COVID clinical evaluation, research and impact on society: a global expert consensus.","authors":"Andrew G Ewing, David Joffe, Svetlana Blitshteyn, Anna E S Brooks, Julien Wist, Yaneer Bar-Yam, Stephane Bilodeau, Jennifer Curtin, Rae Duncan, Mark Faghy, Leo Galland, Etheresia Pretorius, Spela Salamon, Danilo Buonsenso, Claire Hastie, Binita Kane, M Asad Khan, Amos Lal, Dennis Lau, Raina MacIntyre, Sammie McFarland, Daniel Munblit, Jeremy Nicholson, Hanna M Ollila, David Putrino, Alberto Rosario, Timothy Tan","doi":"10.1186/s12941-025-00793-9","DOIUrl":"10.1186/s12941-025-00793-9","url":null,"abstract":"<p><strong>Background: </strong>Long COVID is a complex, heterogeneous syndrome affecting over four hundred million people globally. There are few recommendations, and no formal training exists for medical professionals to assist with clinical evaluation and management of patients with Long COVID. More research into the pathology, cellular, and molecular mechanisms of Long COVID, and treatments is needed. The goal of this work is to disseminate essential information about Long COVID and recommendations about definition, diagnosis, treatment, research and social issues to physicians, researchers, and policy makers to address this escalating global health crisis.</p><p><strong>Methods: </strong>A 3-round modified Delphi consensus methodology was distributed internationally to 179 healthcare professionals, researchers, and persons with lived experience of Long COVID in 28 countries. Statements were combined into specific areas: definition, diagnosis, treatment, research, and society.</p><p><strong>Results: </strong>The survey resulted in 187 comprehensive statements reaching consensus with the strongest areas being diagnosis and clinical assessment, and general research. We establish conditions for diagnosis of different subgroups within the Long COVID umbrella. Clear consensus was reached that the impacts of COVID-19 infection on children should be a research priority, and additionally on the need to determine the effects of Long COVID on societies and economies. The consensus on COVID and Long COVID is that it affects the nervous system and other organs and is not likely to be observed with initial symptoms. We note, biomarkers are critically needed to address these issues.</p><p><strong>Conclusions: </strong>This work forms initial guidance to address the spectrum of Long COVID as a disease and reinforces the need for translational research and large-scale treatment trials for treatment protocols.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"24 1","pages":"27"},"PeriodicalIF":3.6,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Ceftazidime/avibactam (CZA)-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae has emerged, typically due to mutations in the blaKPC gene. This study aimed to investigate the clinical and microbiological characteristics of patients with CZA-resistant KPC-producing K. pneumoniae, with a focus on comparing strains with KPC variants to those with wild-type KPC.
Methods: Unique adult patients with CZA-resistant KPC-producing K. pneumoniae were identified at Taipei Veterans General Hospital between February 2019 and June 2024. Clinical characteristics and outcomes were recorded, and KPC variants were detected using polymerase chain reaction followed by Sanger sequencing.
Results: A total of 60 cases of CZA-resistant KPC-producing K. pneumoniae were included. The 14-day and in-hospital mortality rates were 20% and 41.7%, respectively. Thirty-six strains (60%) harbored KPC variants, with 22 different types identified. KPC-33 (n = 12) was the most common variant. Previous isolation of carbapenem-resistant K. pneumoniae and prior exposure to CZA were more common in the KPC variant group than in the wild-type KPC group. Strains producing KPC variants showed a higher proportion of CZA minimum inhibitory concentration (MIC) ≥ 64 µg/mL (80.6% vs. 4.2%, p < 0.001) and restored meropenem susceptibility (MIC ≤ 4 µg/mL) (72.2% vs. 0%, p < 0.001) compared to those producing wild-type KPC. Additionally, the 14-day mortality rate was lower in patients infected with KPC variant strains compared to those with wild-type KPC strains (11.5% vs. 36.4%, p = 0.041).
Conclusion: CZA-resistant KPC-producing K. pneumoniae is associated with high mortality. Strains producing KPC variants are more likely to exhibit restored meropenem susceptibility and higher levels of CZA resistance.
背景：产生头孢他啶/阿维巴坦（CZA）耐药肺炎克雷伯菌碳青霉烯酶（KPC）的肺炎克雷伯菌已经出现，通常是由于blaKPC基因突变。本研究旨在探讨cza耐药KPC产肺炎克雷伯菌患者的临床和微生物学特征，重点比较KPC变异菌株与野生型KPC菌株。方法：2019年2月至2024年6月在台北退伍军人总医院鉴定出具有cza耐药性的产kpc肺炎克雷伯菌的独特成人患者。记录临床特征和结果，并使用聚合酶链反应和Sanger测序检测KPC变异。结果：共纳入60例cza耐药产kpc肺炎克雷伯菌。14天和住院死亡率分别为20%和41.7%。36株（60%）携带KPC变体，鉴定出22种不同类型。KPC-33 （n = 12）是最常见的变异。与野生型KPC组相比，先前分离出碳青霉烯类耐药肺炎克雷伯菌和先前暴露于CZA的情况在KPC变异组中更为常见。产KPC变异株CZA最小抑制浓度(MIC)≥64µg/mL的比例更高（80.6% vs. 4.2%, p）。结论：产KPC产CZA耐药肺炎克雷伯菌死亡率高。产生KPC变异的菌株更有可能表现出恢复的美罗培南敏感性和更高水平的CZA抗性。
{"title":"Clinical and Microbiological characteristics of patients with ceftazidime/avibactam-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains.","authors":"Szu-Yu Liu, Sheng-Hua Chou, Chien Chuang, Chih-Han Juan, Yu-Chien Ho, Hsiang-Ling Ho, Liang Chen, Yi-Tsung Lin","doi":"10.1186/s12941-025-00797-5","DOIUrl":"https://doi.org/10.1186/s12941-025-00797-5","url":null,"abstract":"<p><strong>Background: </strong>Ceftazidime/avibactam (CZA)-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae has emerged, typically due to mutations in the bla<sub>KPC</sub> gene. This study aimed to investigate the clinical and microbiological characteristics of patients with CZA-resistant KPC-producing K. pneumoniae, with a focus on comparing strains with KPC variants to those with wild-type KPC.</p><p><strong>Methods: </strong>Unique adult patients with CZA-resistant KPC-producing K. pneumoniae were identified at Taipei Veterans General Hospital between February 2019 and June 2024. Clinical characteristics and outcomes were recorded, and KPC variants were detected using polymerase chain reaction followed by Sanger sequencing.</p><p><strong>Results: </strong>A total of 60 cases of CZA-resistant KPC-producing K. pneumoniae were included. The 14-day and in-hospital mortality rates were 20% and 41.7%, respectively. Thirty-six strains (60%) harbored KPC variants, with 22 different types identified. KPC-33 (n = 12) was the most common variant. Previous isolation of carbapenem-resistant K. pneumoniae and prior exposure to CZA were more common in the KPC variant group than in the wild-type KPC group. Strains producing KPC variants showed a higher proportion of CZA minimum inhibitory concentration (MIC) ≥ 64 µg/mL (80.6% vs. 4.2%, p < 0.001) and restored meropenem susceptibility (MIC ≤ 4 µg/mL) (72.2% vs. 0%, p < 0.001) compared to those producing wild-type KPC. Additionally, the 14-day mortality rate was lower in patients infected with KPC variant strains compared to those with wild-type KPC strains (11.5% vs. 36.4%, p = 0.041).</p><p><strong>Conclusion: </strong>CZA-resistant KPC-producing K. pneumoniae is associated with high mortality. Strains producing KPC variants are more likely to exhibit restored meropenem susceptibility and higher levels of CZA resistance.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"24 1","pages":"26"},"PeriodicalIF":4.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><strong>Background: </strong>The emergence and spread of drug resistance to antimalarial drugs pose a severe threat to effective malaria control and treatment. Although sulfadoxine-pyrimethamine resistance is well-documented, it is still the drug of choice for treating intermittent resistance. Molecular markers play a crucial role in tracking and understanding the prevalence of antimalarial drug resistance. Currently, there is insufficient information on the prevalence of molecular markers associated with sulfadoxine-pyrimethamine resistance in P. falciparum.</p><p><strong>Objective: </strong>This systematic review and meta-analysis aimed to determine the pooled prevalence of antimalaria drug resistance-conferring markers associated with sulphadoxine-pyrimethamineine in Plasmodium falciparum in East Africa.</p><p><strong>Methods: </strong>Systematic searche was performed to retrieve articles from PubMed, Scopus, Science Direct databases, and Google Scholar search engine. Sixteen potential studies that provided important data on markers for sulphadoxine-pyrimethamineine resistance in Plasmodium falciparum were systematically reviewed and analyzed. Nine antimalarial drug resistance markers responsible for sulphadoxine-pyrimethamineine resistance in Plasmodium falciparum were extracted separately into Microsoft Excel and analyzed using STATA 17.0. The inverse of variance was done to evaluate heterogeneity across studies. A funnel plot was used to determine the presence of publication bias. A trim-and-fill-meta-analysis was carried out to generate a bias-adjusted effect estimate. A random effect model was used to determine the pooled prevalence of markers responsible for sulphadoxine-pyrimethamineine resistance. Subgroup analysis was performed based on country and year of publication.</p><p><strong>Results: </strong>A total of 16 studies were included for this systematic review and meta-analysis.The molecular markers like dhfr (N51I, C59R, S108N, 108N, 59R, and I164L), and dhps (A437G, K540E, & 540E) were selected for meta-analysis. From this meta-analysis, the pooled prevalence of dhfr N51I, dhfr C59R, dhfr S108N, dhfr 108N, dhfr 59R, and dhfr I164L was 88.6%, 85.3%, 89.6%, 92.2%, 71.5%, and 3.9%, respectively. Likewise, the aggregated prevalence of dhps A437G, dhps K540E, and dhps 540E was 90.2%, 80.9%, and 91.5%, respectively. The subgroup analysis based on year of publication showed that the pooled prevalence of dhfr N51I, dhfr C59R, dhfr S108N, dhps A437G, and dhps K540E, in studies conducted 2014-2018 was 97.11%, 90.57%, 96.45%, 90.89%, and 89.45%, respectively, while it was 82.03%, 81.78%, 85.12%, 89.24%, and 73.98%, respectively, in studies conducted 2019-2023. On the other hand, country-based analysis showed that the pooled prevalence of dhfr N51I, dhfr C59R, dhfr S108N, dhps A437G, and dhps K540E, in Kenya was 85.88%, 84.02%, 86.56%, 90.7%, and 77.55%, respectively.</p><p><strong>Conclusions: </strong>This systematic review and meta-anal
{"title":"Prevalence of antimalaria drug resistance-conferring mutations associated with sulphadoxine-pyrimethamineine-resistant Plasmodium falciparum in East Africa: a systematic review and meta-analysis.","authors":"Wagaw Abebe, Agenagnew Ashagre, Tadesse Misganaw, Zelalem Dejazmach, Getinet Kumie, Marye Nigatie, Abdu Jemal, Zelalem Asmare, Woldeteklehaymanot Kassahun, Solomon Gedfie, Ermias Getachew, Muluken Gashaw, Sisay Ayana, Yalewayker Gashaw, Assefa Sisay, Selamyhun Tadesse, Tegegne Eshetu, Mulat Awoke, Birhanu Kassanew, Atitegeb Abera Kidie, Biruk Beletew Abate, Melese Abate Reta","doi":"10.1186/s12941-025-00795-7","DOIUrl":"10.1186/s12941-025-00795-7","url":null,"abstract":"<p><strong>Background: </strong>The emergence and spread of drug resistance to antimalarial drugs pose a severe threat to effective malaria control and treatment. Although sulfadoxine-pyrimethamine resistance is well-documented, it is still the drug of choice for treating intermittent resistance. Molecular markers play a crucial role in tracking and understanding the prevalence of antimalarial drug resistance. Currently, there is insufficient information on the prevalence of molecular markers associated with sulfadoxine-pyrimethamine resistance in P. falciparum.</p><p><strong>Objective: </strong>This systematic review and meta-analysis aimed to determine the pooled prevalence of antimalaria drug resistance-conferring markers associated with sulphadoxine-pyrimethamineine in Plasmodium falciparum in East Africa.</p><p><strong>Methods: </strong>Systematic searche was performed to retrieve articles from PubMed, Scopus, Science Direct databases, and Google Scholar search engine. Sixteen potential studies that provided important data on markers for sulphadoxine-pyrimethamineine resistance in Plasmodium falciparum were systematically reviewed and analyzed. Nine antimalarial drug resistance markers responsible for sulphadoxine-pyrimethamineine resistance in Plasmodium falciparum were extracted separately into Microsoft Excel and analyzed using STATA 17.0. The inverse of variance was done to evaluate heterogeneity across studies. A funnel plot was used to determine the presence of publication bias. A trim-and-fill-meta-analysis was carried out to generate a bias-adjusted effect estimate. A random effect model was used to determine the pooled prevalence of markers responsible for sulphadoxine-pyrimethamineine resistance. Subgroup analysis was performed based on country and year of publication.</p><p><strong>Results: </strong>A total of 16 studies were included for this systematic review and meta-analysis.The molecular markers like dhfr (N51I, C59R, S108N, 108N, 59R, and I164L), and dhps (A437G, K540E, & 540E) were selected for meta-analysis. From this meta-analysis, the pooled prevalence of dhfr N51I, dhfr C59R, dhfr S108N, dhfr 108N, dhfr 59R, and dhfr I164L was 88.6%, 85.3%, 89.6%, 92.2%, 71.5%, and 3.9%, respectively. Likewise, the aggregated prevalence of dhps A437G, dhps K540E, and dhps 540E was 90.2%, 80.9%, and 91.5%, respectively. The subgroup analysis based on year of publication showed that the pooled prevalence of dhfr N51I, dhfr C59R, dhfr S108N, dhps A437G, and dhps K540E, in studies conducted 2014-2018 was 97.11%, 90.57%, 96.45%, 90.89%, and 89.45%, respectively, while it was 82.03%, 81.78%, 85.12%, 89.24%, and 73.98%, respectively, in studies conducted 2019-2023. On the other hand, country-based analysis showed that the pooled prevalence of dhfr N51I, dhfr C59R, dhfr S108N, dhps A437G, and dhps K540E, in Kenya was 85.88%, 84.02%, 86.56%, 90.7%, and 77.55%, respectively.</p><p><strong>Conclusions: </strong>This systematic review and meta-anal","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"24 1","pages":"25"},"PeriodicalIF":3.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-13DOI: 10.1186/s12941-025-00790-y
Toka A Hakim, Bishoy Maher Zaki, Dalia A Mohamed, Bob Blasdel, Mohamed A Gad, Mohamed S Fayez, Ayman El-Shibiny
Background: Endodontic treatment failures are predominantly attributed to Enterococcus faecalis (E. faecalis) infection, a Gram-positive coccus. E. faecalis forms biofilms, resist multiple antibiotics, and can withstand endodontic disinfection protocols. Vancomycin-resistant strains, in particular, are challenging to treat and are associated with serious medical complications.
Methods: A novel phage, vB_EfaS_ZC1, was isolated and characterized. Its lytic activity against E. faecalis was assessed in vitro through time-killing and biofilm assays. The phage's stability under various conditions was determined. Genomic analysis was conducted to characterize the phage and its virulence. The phage, propolis, and their combination were evaluated as an intracanal irrigation solution against a 4-week E. faecalis mature biofilm, using an ex vivo infected human dentin model. The antibiofilm activity was analyzed using a colony-forming unit assay, field emission scanning electron microscopy, and confocal laser scanning microscopy.
Results: The isolated phage, vB_EfaS_ZC1, a siphovirus with prolate capsid, exhibited strong lytic activity against Vancomycin-resistant strains. In vitro assays indicated its effectiveness in inhibiting planktonic growth and disrupting mature biofilms. The phage remained stable under wide range of temperatures (- 80 to 60 °C), tolerated pH levels from 4 to 11; however the phage viability significantly reduced after UV exposure. Genomic analysis strongly suggests the phage's virulence and suitability for therapeutic applications; neither lysogeny markers nor antibiotic resistance markers were identified. Phylogenetic analysis clustered vB_EfaS_ZC1 within the genus Saphexavirus. The phage, both alone and in combination with propolis, demonstrated potent antibiofilm effects compared to conventional root canal irrigation.
Conclusion: Phage vB_EfaS_ZC1 demonstrates a promising therapy, either individually or in combination with propolis, for addressing challenging endodontic infections caused by E. faecalis.
{"title":"Novel strategies for vancomycin-resistant Enterococcus faecalis biofilm control: bacteriophage (vB_EfaS_ZC1), propolis, and their combined effects in an ex vivo endodontic model.","authors":"Toka A Hakim, Bishoy Maher Zaki, Dalia A Mohamed, Bob Blasdel, Mohamed A Gad, Mohamed S Fayez, Ayman El-Shibiny","doi":"10.1186/s12941-025-00790-y","DOIUrl":"https://doi.org/10.1186/s12941-025-00790-y","url":null,"abstract":"<p><strong>Background: </strong>Endodontic treatment failures are predominantly attributed to Enterococcus faecalis (E. faecalis) infection, a Gram-positive coccus. E. faecalis forms biofilms, resist multiple antibiotics, and can withstand endodontic disinfection protocols. Vancomycin-resistant strains, in particular, are challenging to treat and are associated with serious medical complications.</p><p><strong>Methods: </strong>A novel phage, vB_EfaS_ZC1, was isolated and characterized. Its lytic activity against E. faecalis was assessed in vitro through time-killing and biofilm assays. The phage's stability under various conditions was determined. Genomic analysis was conducted to characterize the phage and its virulence. The phage, propolis, and their combination were evaluated as an intracanal irrigation solution against a 4-week E. faecalis mature biofilm, using an ex vivo infected human dentin model. The antibiofilm activity was analyzed using a colony-forming unit assay, field emission scanning electron microscopy, and confocal laser scanning microscopy.</p><p><strong>Results: </strong>The isolated phage, vB_EfaS_ZC1, a siphovirus with prolate capsid, exhibited strong lytic activity against Vancomycin-resistant strains. In vitro assays indicated its effectiveness in inhibiting planktonic growth and disrupting mature biofilms. The phage remained stable under wide range of temperatures (- 80 to 60 °C), tolerated pH levels from 4 to 11; however the phage viability significantly reduced after UV exposure. Genomic analysis strongly suggests the phage's virulence and suitability for therapeutic applications; neither lysogeny markers nor antibiotic resistance markers were identified. Phylogenetic analysis clustered vB_EfaS_ZC1 within the genus Saphexavirus. The phage, both alone and in combination with propolis, demonstrated potent antibiofilm effects compared to conventional root canal irrigation.</p><p><strong>Conclusion: </strong>Phage vB_EfaS_ZC1 demonstrates a promising therapy, either individually or in combination with propolis, for addressing challenging endodontic infections caused by E. faecalis.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"24 1","pages":"24"},"PeriodicalIF":4.6,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-13DOI: 10.1186/s12941-025-00792-w
Emanuele Palomba, Agnese Comelli, Francesca Saluzzo, Federico Di Marco, Elisa Matarazzo, Noemi Lo Re, Alessandra Bielli, Chiara Silvia Vismara, Antonio Muscatello, Marianna Rossi, Daniela Maria Cirillo, Alessandra Bandera, Andrea Gori
Background: Antimicrobial resistance in Enterobacterales represents a substantial threat in modern clinical practice and the collection of data on the efficacy of new molecules is of paramount importance. Our study aimed to analyse the in vitro activity of imipenem/cilastatin/relebactam (IMI/REL) against KPC-producing Klebsiella pneumoniae (KPC-Kp) and investigate the genetic determinants of resistance to this agent.
Methods: A total of 603 KPC-Kp strains, which were randomly collected during a multicentre study in northern Italy in the period 2016-2018, were analysed retrospectively. Antibiotic susceptibility testing was performed using a commercial broth microdilution. IMI-REL-resistant KPC-Kp strains were further analysed by whole genome sequencing to identify resistance determinants.
Results: Ninety-eight percent of KPC-Kp (591/603) showed in vitro susceptibility to IMI/REL, with a minimum inhibitory concentration below the EUCAST cut-off. Different mutations in OmpK36 were found in all 12 IMI/REL-resistant strains, which belonged to MLST STs 258 (3 isolates), 307 (8 isolates) and 512 (1 isolate), but no clonal relatedness was detected by the minimum spanning tree analysis, except for 2 strains isolated in the same hospital. Equal distribution of blaKPC-2 (6/12) and blaKPC-3 (6/12) was found, and in 11 isolates the presence of genetic variants associated with the production of beta-lactamases was also identified. KPC-Kp resistant to IMI/REL retained susceptibility to meropenem/vaborbactam (MVB, 12/12, 100%) and ceftazidime/avibactam (CZA, 11/12, 91.7%). Only one strain of 603 was resistant to either MVB and CZA but susceptible to IMI/REL with a MIC of 2 mg/L; 4/603 (0.7%) were resistant to CZA but susceptible to IMI/REL and MVB.
Conclusions: IMI/REL showed good in vitro activity against the KPC-Kp strains analysed. All the IMI/REL-resistant strains displayed a mutation in porin OmpK36 and produced carbapenemases, with KPC-2 and KPC-3 being equally distributed. MVB and CZA maintained good activity against IMI/REL resistant isolates.
{"title":"Activity of imipenem/relebactam against KPC-producing Klebsiella pneumoniae and the possible role of Ompk36 mutation in determining resistance: an Italian retrospective analysis.","authors":"Emanuele Palomba, Agnese Comelli, Francesca Saluzzo, Federico Di Marco, Elisa Matarazzo, Noemi Lo Re, Alessandra Bielli, Chiara Silvia Vismara, Antonio Muscatello, Marianna Rossi, Daniela Maria Cirillo, Alessandra Bandera, Andrea Gori","doi":"10.1186/s12941-025-00792-w","DOIUrl":"https://doi.org/10.1186/s12941-025-00792-w","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial resistance in Enterobacterales represents a substantial threat in modern clinical practice and the collection of data on the efficacy of new molecules is of paramount importance. Our study aimed to analyse the in vitro activity of imipenem/cilastatin/relebactam (IMI/REL) against KPC-producing Klebsiella pneumoniae (KPC-Kp) and investigate the genetic determinants of resistance to this agent.</p><p><strong>Methods: </strong>A total of 603 KPC-Kp strains, which were randomly collected during a multicentre study in northern Italy in the period 2016-2018, were analysed retrospectively. Antibiotic susceptibility testing was performed using a commercial broth microdilution. IMI-REL-resistant KPC-Kp strains were further analysed by whole genome sequencing to identify resistance determinants.</p><p><strong>Results: </strong>Ninety-eight percent of KPC-Kp (591/603) showed in vitro susceptibility to IMI/REL, with a minimum inhibitory concentration below the EUCAST cut-off. Different mutations in OmpK36 were found in all 12 IMI/REL-resistant strains, which belonged to MLST STs 258 (3 isolates), 307 (8 isolates) and 512 (1 isolate), but no clonal relatedness was detected by the minimum spanning tree analysis, except for 2 strains isolated in the same hospital. Equal distribution of bla<sub>KPC-2</sub> (6/12) and bla<sub>KPC-3</sub> (6/12) was found, and in 11 isolates the presence of genetic variants associated with the production of beta-lactamases was also identified. KPC-Kp resistant to IMI/REL retained susceptibility to meropenem/vaborbactam (MVB, 12/12, 100%) and ceftazidime/avibactam (CZA, 11/12, 91.7%). Only one strain of 603 was resistant to either MVB and CZA but susceptible to IMI/REL with a MIC of 2 mg/L; 4/603 (0.7%) were resistant to CZA but susceptible to IMI/REL and MVB.</p><p><strong>Conclusions: </strong>IMI/REL showed good in vitro activity against the KPC-Kp strains analysed. All the IMI/REL-resistant strains displayed a mutation in porin OmpK36 and produced carbapenemases, with KPC-2 and KPC-3 being equally distributed. MVB and CZA maintained good activity against IMI/REL resistant isolates.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"24 1","pages":"23"},"PeriodicalIF":4.6,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-05DOI: 10.1186/s12941-025-00787-7
Connie T Y Xie, Samantha Martinez, Ceylon V Simon, Susan M Poutanen
Background: Stratified antibiograms are recommended to guide empiric clinical treatment. However, which strata to focus on, the limited number of isolates in identified strata, and the heavy associated workload all pose challenges. This study compares differences in antibiotic susceptibility between a hospital-wide, all-specimens antibiogram and stratified antibiograms in order to identify the value-added of antibiogram stratification.
Method: Antibiotic susceptibility of bacterial isolates from 2021 at a quaternary-care academic hospital was obtained from published hospital-wide and unit- and specimen-specific stratified antibiograms. Differences in percent susceptibility by organism and drug between the hospital-wide and stratified antibiograms were calculated. Weighted averages of the difference in percent susceptibility were calculated for each stratified antibiogram compared to the hospital-wide antibiogram and unit-wide antibiograms. Differences were shown through heat maps.
Results: When compared to a hospital-wide, all-specimens antibiogram, the emergency department (ED) antibiogram showed higher susceptibility, whereas the intensive care unit (ICU) and, particularly, the transplant unit antibiograms exhibited reduced susceptibility. Compared to unit level antibiograms, further stratification within each unit to specimen-specific (syndromic) antibiograms revealed additional differences. In the ED, urine and respiratory-stratified antibiograms had lower susceptibility and blood had higher susceptibility. Compared to unit-specific antibiograms, in the ICU, all specimen-stratified antibiograms had lower susceptibility and in the transplant unit, antibiograms for all specimens but urine had lower susceptibility.
Conclusion: Using a hospital-wide all-specimens antibiogram may both overcall and under call susceptibility leading to poor empiric antimicrobial choices. Specimen-specific antibiograms stratified by unit best inform empiric therapy for specific populations.
{"title":"An analysis of the value-added of antibiogram subgroup stratification.","authors":"Connie T Y Xie, Samantha Martinez, Ceylon V Simon, Susan M Poutanen","doi":"10.1186/s12941-025-00787-7","DOIUrl":"10.1186/s12941-025-00787-7","url":null,"abstract":"<p><strong>Background: </strong>Stratified antibiograms are recommended to guide empiric clinical treatment. However, which strata to focus on, the limited number of isolates in identified strata, and the heavy associated workload all pose challenges. This study compares differences in antibiotic susceptibility between a hospital-wide, all-specimens antibiogram and stratified antibiograms in order to identify the value-added of antibiogram stratification.</p><p><strong>Method: </strong>Antibiotic susceptibility of bacterial isolates from 2021 at a quaternary-care academic hospital was obtained from published hospital-wide and unit- and specimen-specific stratified antibiograms. Differences in percent susceptibility by organism and drug between the hospital-wide and stratified antibiograms were calculated. Weighted averages of the difference in percent susceptibility were calculated for each stratified antibiogram compared to the hospital-wide antibiogram and unit-wide antibiograms. Differences were shown through heat maps.</p><p><strong>Results: </strong>When compared to a hospital-wide, all-specimens antibiogram, the emergency department (ED) antibiogram showed higher susceptibility, whereas the intensive care unit (ICU) and, particularly, the transplant unit antibiograms exhibited reduced susceptibility. Compared to unit level antibiograms, further stratification within each unit to specimen-specific (syndromic) antibiograms revealed additional differences. In the ED, urine and respiratory-stratified antibiograms had lower susceptibility and blood had higher susceptibility. Compared to unit-specific antibiograms, in the ICU, all specimen-stratified antibiograms had lower susceptibility and in the transplant unit, antibiograms for all specimens but urine had lower susceptibility.</p><p><strong>Conclusion: </strong>Using a hospital-wide all-specimens antibiogram may both overcall and under call susceptibility leading to poor empiric antimicrobial choices. Specimen-specific antibiograms stratified by unit best inform empiric therapy for specific populations.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"24 1","pages":"21"},"PeriodicalIF":4.6,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-05DOI: 10.1186/s12941-025-00791-x
Chen Yang, Yue-Xin Zheng, Hong-Yi Gu, Hong Chen, Wei Li, Fang Li, Yu-Wang Bi, Jing Chen, Fu-Kun Wang, Qing-Qing Sun, Han-Bing Meng, Zuo-Hao Wu, Shu Yu, Jiang Gu, Yan Cheng
<p><strong>Background: </strong>Nocardia cyriacigeorgica, an opportunistic pathogen, is increasingly implicated in human infections. This pathogen predominantly causes pulmonary infections, leading to acute, subacute, or chronic necrotizing suppurative lesions, in severe cases, may progress to disseminated infections. Effective clinical diagnosis, prevention, and treatment strategies require a thorough understanding of its biological characteristics and pathogenic mechanisms. However, despite the rising incidence of nocardial diseases, research on the pathogenicity of N. cyriacigeorgica remains limited, primarily focusing on case reports and epidemiological studies. This study aimed to provide a comprehensive analysis of the genomic features, phylogenetic relationships, antimicrobial resistance profiles, and candidate virulence factors of N. cyriacigeorgica strains to inform future investigations into its pathogenesis.</p><p><strong>Methods: </strong>Whole-genome sequencing was conducted on five N. cyriacigeorgica strains isolated from patients with pulmonary infection at our hospital. This analysis utilized a combination of second-generation Illumina HiSeq and third-generation PacBio sequencing technologies. Additionally, publicly available genomic data from 58 strains in the National Center Biotechnology Information database were integrated, resulting in a dataset of 63 genomes. These genomes were subjected to comparative genomic analyses, including phylogenetic reconstruction, pan-genome evaluation, and gene distribution assessments.</p><p><strong>Results: </strong>Phylogenetic analysis identified five major clades within N. cyriacigeorgica. ANI analysis further subdivided clade B into five distinct subgroups. Pan-genome analysis revealed clade-specific orthogroups in the distribution of genes assigned to Clusters of Orthologous Groups, with clade A containing the highest number of clade-specific gene families. Comparative genomic analysis uncovered several potential pathogenic genes implicated in host cell invasion, phagosomal maturation arrest, and intracellular survival within macrophages, which were conserved across all analyzed strains. Notable differences in the distribution of enterobactin-encoding genes were observed among the clades. The mce3C gene also displayed variable distributions across clades; however, no correlation was established between its presence and strain source. Among the 63 strains, 27 were found to harbor both mce3C and mce4F genes, which were categorized into five distinct patterns. Furthermore, antibiotic resistance genes, including VanSO, VanRO, erm(O)-Irm, srmB, ermH, bcl, bla1, and cmIR, demonstrated clade-specific distribution patterns. Notably, the genes erm(O)-Irm, srmB, and ermH were associated with the isolation origin of the strains.</p><p><strong>Conclusions: </strong>This study provides a comprehensive evaluation of the genomic characteristics, potential virulence factors, antimicrobial resistance genes
背景：Nocardia cyriacigeorgica 是一种机会性病原体，越来越多地与人类感染有关。这种病原体主要引起肺部感染，导致急性、亚急性或慢性坏死性化脓性病变，严重时可发展为播散性感染。有效的临床诊断、预防和治疗策略需要对其生物学特征和致病机制有透彻的了解。然而，尽管N. cyriacigeorgica的发病率不断上升，但对其致病性的研究仍然有限，主要集中在病例报告和流行病学研究上。本研究旨在全面分析 N. cyriacigeorgica 菌株的基因组特征、系统发育关系、抗菌药耐药性特征和候选致病因子，为今后研究其致病机理提供依据：方法：对从本院肺部感染患者中分离出的五株 N. cyriacigeorgica 进行了全基因组测序。该分析结合使用了第二代 Illumina HiSeq 和第三代 PacBio 测序技术。此外，还整合了美国国家生物技术信息中心数据库中 58 个菌株的公开基因组数据，从而形成了一个包含 63 个基因组的数据集。对这些基因组进行了比较基因组分析，包括系统发育重建、泛基因组评估和基因分布评估：系统发育分析确定了 N. cyriacigeorgica 的五个主要支系。ANI 分析将支系 B 进一步细分为五个不同的亚群。泛基因组分析显示，在分配给同源群的基因分布中，支系特异性正交群，其中支系 A 包含的支系特异性基因家族数量最多。比较基因组分析发现了几个潜在的致病基因，这些基因与宿主细胞入侵、吞噬体成熟停滞和巨噬细胞内生存有关，在所有分析菌株中都是保守的。在不同支系中，肠杆菌素编码基因的分布存在明显差异。mce3C 基因在不同支系中的分布也不尽相同；不过，该基因的存在与菌株来源之间没有关联。在 63 株菌株中，发现 27 株同时携带 mce3C 和 mce4F 基因，并将其分为五种不同的模式。此外，包括 VanSO、VanRO、erm(O)-Irm、srmB、ermH、bcl、bla1 和 cmIR 在内的抗生素耐药基因也呈现出特定支系的分布模式。值得注意的是，erm（O）-Irm、srmB 和 ermH 基因与菌株的分离来源有关：本研究对 N. cyriacigeorgica 的基因组特征、潜在毒力因子、抗菌药耐药基因和系统发育关系进行了全面评估。研究结果为了解 N. cyriacigeorgica 感染的细胞内生存、在巨噬细胞内复制以及病原体与宿主相互作用的机制提供了宝贵的见解。这些结果为今后研究 N. cyriacigeorgica 的发病机制和临床治疗奠定了基础。
{"title":"Genomic characteristics, virulence potential, antimicrobial resistance profiles, and phylogenetic insights into Nocardia cyriacigeorgica.","authors":"Chen Yang, Yue-Xin Zheng, Hong-Yi Gu, Hong Chen, Wei Li, Fang Li, Yu-Wang Bi, Jing Chen, Fu-Kun Wang, Qing-Qing Sun, Han-Bing Meng, Zuo-Hao Wu, Shu Yu, Jiang Gu, Yan Cheng","doi":"10.1186/s12941-025-00791-x","DOIUrl":"10.1186/s12941-025-00791-x","url":null,"abstract":"<p><strong>Background: </strong>Nocardia cyriacigeorgica, an opportunistic pathogen, is increasingly implicated in human infections. This pathogen predominantly causes pulmonary infections, leading to acute, subacute, or chronic necrotizing suppurative lesions, in severe cases, may progress to disseminated infections. Effective clinical diagnosis, prevention, and treatment strategies require a thorough understanding of its biological characteristics and pathogenic mechanisms. However, despite the rising incidence of nocardial diseases, research on the pathogenicity of N. cyriacigeorgica remains limited, primarily focusing on case reports and epidemiological studies. This study aimed to provide a comprehensive analysis of the genomic features, phylogenetic relationships, antimicrobial resistance profiles, and candidate virulence factors of N. cyriacigeorgica strains to inform future investigations into its pathogenesis.</p><p><strong>Methods: </strong>Whole-genome sequencing was conducted on five N. cyriacigeorgica strains isolated from patients with pulmonary infection at our hospital. This analysis utilized a combination of second-generation Illumina HiSeq and third-generation PacBio sequencing technologies. Additionally, publicly available genomic data from 58 strains in the National Center Biotechnology Information database were integrated, resulting in a dataset of 63 genomes. These genomes were subjected to comparative genomic analyses, including phylogenetic reconstruction, pan-genome evaluation, and gene distribution assessments.</p><p><strong>Results: </strong>Phylogenetic analysis identified five major clades within N. cyriacigeorgica. ANI analysis further subdivided clade B into five distinct subgroups. Pan-genome analysis revealed clade-specific orthogroups in the distribution of genes assigned to Clusters of Orthologous Groups, with clade A containing the highest number of clade-specific gene families. Comparative genomic analysis uncovered several potential pathogenic genes implicated in host cell invasion, phagosomal maturation arrest, and intracellular survival within macrophages, which were conserved across all analyzed strains. Notable differences in the distribution of enterobactin-encoding genes were observed among the clades. The mce3C gene also displayed variable distributions across clades; however, no correlation was established between its presence and strain source. Among the 63 strains, 27 were found to harbor both mce3C and mce4F genes, which were categorized into five distinct patterns. Furthermore, antibiotic resistance genes, including VanSO, VanRO, erm(O)-Irm, srmB, ermH, bcl, bla1, and cmIR, demonstrated clade-specific distribution patterns. Notably, the genes erm(O)-Irm, srmB, and ermH were associated with the isolation origin of the strains.</p><p><strong>Conclusions: </strong>This study provides a comprehensive evaluation of the genomic characteristics, potential virulence factors, antimicrobial resistance genes","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"24 1","pages":"22"},"PeriodicalIF":4.6,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Cefiderocol, a newly introduced siderophore cephalosporin, exhibits activity against various multidrug-resistant (MDR) Gram-negative bacilli (GNB), including producers of Ambler class A, B and D carbapenemases. The TROJAN-MDR study aimed to (i) compare the in vitro activity of cefiderocol with other last-resort antibiotics against a well-characterized collection of Enterobacterales and Pseudomonas aeruginosa strains from Southern France, and (ii) assess the performance of available cefiderocol antimicrobial susceptibility testing (AST) methods.
Methods: The collection comprised 127 Enterobacterales from various clones, including 119 carbapenemase producers (93.7%), and 53 MDR P. aeruginosa. The minimum inhibitory concentrations (MICs) of cefiderocol were determined using the UMIC® broth microdilution method (BMD) as the reference. Comparators MICs were measured using Sensititre™ EUMDRXXF plates and Liofilchem strips for aztreonam-avibactam. Results were interpreted according to EUCAST breakpoints, with CLSI breakpoints also used for cefiderocol. The performance of the ComASP® BMD and disk diffusion on two different Mueller-Hinton media (Bio-Rad and BD) were evaluated according to ISO 20776-2:2007 and 2021.
Results: Cefiderocol demonstrated potent activity on Enterobacterales (81.9% susceptible) and P. aeruginosa (84.9%) using EUCAST breakpoints. Among Enterobacterales, the most effective comparators were colistin, aztreonam-avibactam, meropenem-vaborbactam, and amikacin, with susceptibility rates of 99.2%, 98.4%, 85%, and 76.4%, respectively. For P. aeruginosa, only colistin exhibited better activity (100%). The disk diffusion method showed superior performance on BD medium compared to Bio-Rad. The ComASP® method did not provide sufficient performance to be considered reliable.
Conclusions: Cefiderocol was highly active against a large collection of MDR GNB, including high-risk clones. It is crucial to assess susceptibility to this last-resort antibiotic using a validated method when considering clinical use.
{"title":"TROJAN-MDR: in vitro activity of cefiderocol and comparators against multidrug-resistant Enterobacterales and Pseudomonas aeruginosa strains in Southern France, evaluation of available testing methods performances.","authors":"Massinissa Benyahia, Chloé Magnan, Vincent Jean-Pierre, Romaric Larcher, Adeline Boutet-Dubois, Marie Gaillard, Hélène Marchandin, Stéphanie Genieyz, Madjid Morsli, Jean-Philippe Lavigne, Alix Pantel","doi":"10.1186/s12941-025-00785-9","DOIUrl":"10.1186/s12941-025-00785-9","url":null,"abstract":"<p><strong>Background: </strong> Cefiderocol, a newly introduced siderophore cephalosporin, exhibits activity against various multidrug-resistant (MDR) Gram-negative bacilli (GNB), including producers of Ambler class A, B and D carbapenemases. The TROJAN-MDR study aimed to (i) compare the in vitro activity of cefiderocol with other last-resort antibiotics against a well-characterized collection of Enterobacterales and Pseudomonas aeruginosa strains from Southern France, and (ii) assess the performance of available cefiderocol antimicrobial susceptibility testing (AST) methods.</p><p><strong>Methods: </strong>The collection comprised 127 Enterobacterales from various clones, including 119 carbapenemase producers (93.7%), and 53 MDR P. aeruginosa. The minimum inhibitory concentrations (MICs) of cefiderocol were determined using the UMIC<sup>®</sup> broth microdilution method (BMD) as the reference. Comparators MICs were measured using Sensititre™ EUMDRXXF plates and Liofilchem strips for aztreonam-avibactam. Results were interpreted according to EUCAST breakpoints, with CLSI breakpoints also used for cefiderocol. The performance of the ComASP<sup>®</sup> BMD and disk diffusion on two different Mueller-Hinton media (Bio-Rad and BD) were evaluated according to ISO 20776-2:2007 and 2021.</p><p><strong>Results: </strong>Cefiderocol demonstrated potent activity on Enterobacterales (81.9% susceptible) and P. aeruginosa (84.9%) using EUCAST breakpoints. Among Enterobacterales, the most effective comparators were colistin, aztreonam-avibactam, meropenem-vaborbactam, and amikacin, with susceptibility rates of 99.2%, 98.4%, 85%, and 76.4%, respectively. For P. aeruginosa, only colistin exhibited better activity (100%). The disk diffusion method showed superior performance on BD medium compared to Bio-Rad. The ComASP<sup>®</sup> method did not provide sufficient performance to be considered reliable.</p><p><strong>Conclusions: </strong>Cefiderocol was highly active against a large collection of MDR GNB, including high-risk clones. It is crucial to assess susceptibility to this last-resort antibiotic using a validated method when considering clinical use.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"24 1","pages":"20"},"PeriodicalIF":4.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: This study aimed to assess the resistance phenotype, virulence phenotype, and genetic characteristics of a blaNDM-1 and blaSHV-12 co-harboring ST65 K2 Klebsiella pneumoniae (KP114), which was isolated from General hospital of Ningxia Medical University.
Methods: Antibiotic susceptibility test was determined by Vitek 2 Compact system. Multilocus Sequence typing (MLST), antimicrobial resistance and virulence genes were examined by PCR and Sanger sequencing. The virulence of KP114 was evaluated through string test, macrophage phagocytosis assay, serum resistance assay, and mouse infection model. Whole-genome sequencing was performed for further analysis of genetic information.
Results: The presence of the blaNDM-1 and blaSHV-12 genes in KP114 confered resistance to multi-antibiotics. The hypervirulence of KP114 was demonstrated through various in vitro experiments and in vivo mouse infection model. KP114 was found to harbor two distinct plasmids: a drug-resistant plasmid (pKP114-NDM), classified as the IncX3 type, which contained various transfer elements including type IV coupling protein (T4CP) and type IV secretion system (T4SS), and a virulence plasmid (pKP114-vir) that exhibited a high sequence similarity with pLVPK. The results of the conjugation experiment showed that resistance and virulence traits were successfully transferred from KP114 to Escherichia coli EC600 and J53.
Conclusions: We reported a Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) strain of ST65 K2 serotype carrying the blaNDM-1 and blaSHV-12, which exhibited hypervirulence and drug resistance with potential for transmission. This finding allows improved clinical surveillance and control of this clone, thereby holding considerable value for clinical treatment.
{"title":"Molecular and genetic features of a bla<sub>NDM-1</sub> and bla<sub>SHV-12</sub> coharboring hypermucoviscous Klebsiella pneumoniae of serotype K2 and ST65.","authors":"Yuting Kang, Qiujie Li, Wanting Ma, Chao Xu, Zhuoran Qiu, Wei Jia, Pengtao Wang","doi":"10.1186/s12941-025-00789-5","DOIUrl":"10.1186/s12941-025-00789-5","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to assess the resistance phenotype, virulence phenotype, and genetic characteristics of a bla<sub>NDM-1</sub> and bla<sub>SHV-12</sub> co-harboring ST65 K2 Klebsiella pneumoniae (KP114), which was isolated from General hospital of Ningxia Medical University.</p><p><strong>Methods: </strong>Antibiotic susceptibility test was determined by Vitek 2 Compact system. Multilocus Sequence typing (MLST), antimicrobial resistance and virulence genes were examined by PCR and Sanger sequencing. The virulence of KP114 was evaluated through string test, macrophage phagocytosis assay, serum resistance assay, and mouse infection model. Whole-genome sequencing was performed for further analysis of genetic information.</p><p><strong>Results: </strong>The presence of the bla<sub>NDM-1</sub> and bla<sub>SHV-12</sub> genes in KP114 confered resistance to multi-antibiotics. The hypervirulence of KP114 was demonstrated through various in vitro experiments and in vivo mouse infection model. KP114 was found to harbor two distinct plasmids: a drug-resistant plasmid (pKP114-NDM), classified as the IncX3 type, which contained various transfer elements including type IV coupling protein (T4CP) and type IV secretion system (T4SS), and a virulence plasmid (pKP114-vir) that exhibited a high sequence similarity with pLVPK. The results of the conjugation experiment showed that resistance and virulence traits were successfully transferred from KP114 to Escherichia coli EC600 and J53.</p><p><strong>Conclusions: </strong>We reported a Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) strain of ST65 K2 serotype carrying the bla<sub>NDM-1</sub> and bla<sub>SHV-12</sub>, which exhibited hypervirulence and drug resistance with potential for transmission. This finding allows improved clinical surveillance and control of this clone, thereby holding considerable value for clinical treatment.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"24 1","pages":"19"},"PeriodicalIF":4.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-18DOI: 10.1186/s12941-025-00788-6
Somayeh Yaslianifard, Fatemeh Sameni, Kimia Kazemi, Yousef Atefpour, Bahareh Hajikhani, Ali Baradaran Bagheri, Shahrooz Yazdani, Masoud Dadashi
Background: Helicobacter pylori (H. pylori) is known to induce chronic inflammatory conditions, and interactions between the host immune system and pathogen have diverted attention toward investigating its correlation with extra-gastrointestinal disorders.
Objective: The present study aimed to assess the rate of H. pylori infection in cardiovascular disease (CVD) through a systematic review and meta-analysis.
Methods: We conducted a large-scale meta-analysis to determine the prevalence rates of H. pylori infection in vascular diseases. Articles from PubMed/Medline, Web of Science, and Embase databases published between 2000 and 2023 were included for analysis. We used multiple independent observers to extract data, calculated the pooled frequency of H. pylori in vascular diseases using a random effect model, and reported the results as a weighted average based on the study population. The main outcome measures were presented with 95% confidence intervals (CI).
Results: In 87 included studies, the prevalence of H. pylori infection in vascular diseases was 56.7% worldwide. 14.25% of H. pylori isolates harbored the cagA gene. The predominant vascular complication was coronary artery disease (CAD) (31.07%), primarily documented in Europe. This meta-analysis revealed a declining emphasis on studying the association of H. pylori infection with vascular disease in recent times.
Conclusion: According to this meta-analysis, H. pylori infection has a high frequency in CVD and may increase the risk of vascular diseases. However, further research is required, particularly in nations with limited data.
背景：已知幽门螺杆菌（h.p ylori）可诱导慢性炎症，宿主免疫系统和病原体之间的相互作用已将注意力转移到研究其与胃肠道外疾病的相关性上。目的：本研究旨在通过系统回顾和荟萃分析评估心血管疾病（CVD）幽门螺杆菌感染率。方法：我们进行了一项大规模荟萃分析，以确定血管疾病中幽门螺杆菌感染的患病率。2000年至2023年间发表的来自PubMed/Medline、Web of Science和Embase数据库的文章被纳入分析。我们使用多个独立观测者提取数据，使用随机效应模型计算幽门螺杆菌在血管疾病中的合并频率，并以研究人群为基础的加权平均值报告结果。主要结果测量以95%置信区间（CI）表示。结果：在87项纳入的研究中，幽门螺杆菌在血管疾病中的感染率为56.7%。14.25%的幽门螺杆菌含有cagA基因。主要的血管并发症是冠状动脉疾病（CAD）（31.07%），主要记录在欧洲。这项荟萃分析显示，近年来对幽门螺杆菌感染与血管疾病的相关性研究的重视程度有所下降。结论：本荟萃分析显示，幽门螺杆菌感染在心血管疾病中发生率较高，并可能增加血管疾病的发生风险。然而，需要进一步的研究，特别是在数据有限的国家。
{"title":"Beyond the gut: a comprehensive meta-analysis on Helicobacter pylori infection and cardiovascular complications.","authors":"Somayeh Yaslianifard, Fatemeh Sameni, Kimia Kazemi, Yousef Atefpour, Bahareh Hajikhani, Ali Baradaran Bagheri, Shahrooz Yazdani, Masoud Dadashi","doi":"10.1186/s12941-025-00788-6","DOIUrl":"10.1186/s12941-025-00788-6","url":null,"abstract":"<p><strong>Background: </strong>Helicobacter pylori (H. pylori) is known to induce chronic inflammatory conditions, and interactions between the host immune system and pathogen have diverted attention toward investigating its correlation with extra-gastrointestinal disorders.</p><p><strong>Objective: </strong>The present study aimed to assess the rate of H. pylori infection in cardiovascular disease (CVD) through a systematic review and meta-analysis.</p><p><strong>Methods: </strong>We conducted a large-scale meta-analysis to determine the prevalence rates of H. pylori infection in vascular diseases. Articles from PubMed/Medline, Web of Science, and Embase databases published between 2000 and 2023 were included for analysis. We used multiple independent observers to extract data, calculated the pooled frequency of H. pylori in vascular diseases using a random effect model, and reported the results as a weighted average based on the study population. The main outcome measures were presented with 95% confidence intervals (CI).</p><p><strong>Results: </strong>In 87 included studies, the prevalence of H. pylori infection in vascular diseases was 56.7% worldwide. 14.25% of H. pylori isolates harbored the cagA gene. The predominant vascular complication was coronary artery disease (CAD) (31.07%), primarily documented in Europe. This meta-analysis revealed a declining emphasis on studying the association of H. pylori infection with vascular disease in recent times.</p><p><strong>Conclusion: </strong>According to this meta-analysis, H. pylori infection has a high frequency in CVD and may increase the risk of vascular diseases. However, further research is required, particularly in nations with limited data.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"24 1","pages":"18"},"PeriodicalIF":3.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11916874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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