Pub Date : 2024-09-17DOI: 10.1016/j.ijantimicag.2024.107340
Aldeliane M. da Silva , Duber M. Murillo , Silambarasan Anbumani , Antonio Augusto von Zuben , Alessandro Cavalli , Helio T. Obata , Eduarda Regina Fischer , Mariana de Souza e Silva , Erik Bakkers , Alessandra A. Souza , Hernandes F. Carvalho , Mônica A. Cotta
Background
The matrix of extracellular polymeric substances (EPS) present in biofilms greatly amplifies the problem of bacterial infections, protecting bacteria against antimicrobial treatments and eventually leading to bacterial resistance. The need for alternative treatments that destroy the EPS matrix becomes evident. N-acetylcysteine (NAC) is one option that presents diverse effects against bacteria; however, the different mechanisms of action of NAC in biofilms have yet to be elucidated.
Objectives
In this work, we performed microscopy studies at micro and nano scales to address the effects of NAC at single cell level and early-stage biofilms of the Xylella fastidiosa phytopathogen.
Methods
We show the physical effects of NAC on the adhesion surface and the different types of EPS, as well as the mechanical response of individual bacteria to NAC concentrations between 2 and 20 mg/mL.
Results
NAC modified the conditioning film on the substrate, broke down the soluble EPS, resulting in the release of adherent bacteria, decreased the volume of loosely bound EPS, and disrupted the biofilm matrix. Tightly bound EPS suffered structural alterations despite no solid evidence of its removal. In addition, bacterial force measurements upon NAC action performed with InP nanowire arrays showed an enhanced momentum transfer to the nanowires due to increased cell mobility resulting from EPS removal.
Conclusions
Our results clearly show that conditioning film and soluble EPS play a key role in cell adhesion control and that NAC alters EPS structure, providing solid evidence that NAC actuates mainly on EPS removal, both at single cell and biofilm levels.
{"title":"N-acetylcysteine effects on extracellular polymeric substances of Xylella fastidiosa: A spatiotemporal investigation with implications for biofilm disruption","authors":"Aldeliane M. da Silva , Duber M. Murillo , Silambarasan Anbumani , Antonio Augusto von Zuben , Alessandro Cavalli , Helio T. Obata , Eduarda Regina Fischer , Mariana de Souza e Silva , Erik Bakkers , Alessandra A. Souza , Hernandes F. Carvalho , Mônica A. Cotta","doi":"10.1016/j.ijantimicag.2024.107340","DOIUrl":"10.1016/j.ijantimicag.2024.107340","url":null,"abstract":"<div><h3>Background</h3><div>The matrix of extracellular polymeric substances (EPS) present in biofilms greatly amplifies the problem of bacterial infections, protecting bacteria against antimicrobial treatments and eventually leading to bacterial resistance. The need for alternative treatments that destroy the EPS matrix becomes evident. N-acetylcysteine (NAC) is one option that presents diverse effects against bacteria; however, the different mechanisms of action of NAC in biofilms have yet to be elucidated.</div></div><div><h3>Objectives</h3><div>In this work, we performed microscopy studies at micro and nano scales to address the effects of NAC at single cell level and early-stage biofilms of the <em>Xylella fastidiosa</em> phytopathogen.</div></div><div><h3>Methods</h3><div>We show the physical effects of NAC on the adhesion surface and the different types of EPS, as well as the mechanical response of individual bacteria to NAC concentrations between 2 and 20 mg/mL.</div></div><div><h3>Results</h3><div>NAC modified the conditioning film on the substrate, broke down the soluble EPS, resulting in the release of adherent bacteria, decreased the volume of loosely bound EPS, and disrupted the biofilm matrix. Tightly bound EPS suffered structural alterations despite no solid evidence of its removal. In addition, bacterial force measurements upon NAC action performed with InP nanowire arrays showed an enhanced momentum transfer to the nanowires due to increased cell mobility resulting from EPS removal.</div></div><div><h3>Conclusions</h3><div>Our results clearly show that conditioning film and soluble EPS play a key role in cell adhesion control and that NAC alters EPS structure, providing solid evidence that NAC actuates mainly on EPS removal, both at single cell and biofilm levels.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107340"},"PeriodicalIF":4.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1016/j.ijantimicag.2024.107320
Niandi Tan , Hao Wu , Cheng Lan , Chengxia Liu , Aijun Liao , Zhiyong Jiao , Dongxing Su , Xiaomei Zhang , Zhe Zhang , Weiming Xiao , Fangfang Li , Xing Li , Min Xia , Rongyuan Qiu , Huixin Chen , Youli Liu , Mei Su , Minhu Chen , Yinglian Xiao
Introduction
Keverprazan is a novel potassium-competitive acid blocker. The advantages of keverprazan as a potent acid suppressor in Helicobacter pylori eradication have not yet been demonstrated. The aim of this study was to evaluate the efficacy of keverprazan as a component of bismuth quadruple therapy in H. pylori treatment.
Methods
Adult patients with H. pylori infection were enrolled and randomised to take keverprazan (KEV group)- or esomeprazole (ESO group)-quadruple therapy. The regimens contained keverprazan 20 mg or esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 240 mg and were administered twice daily for 14 days. The primary endpoint was the H. pylori eradication rate at 4 weeks after treatment.
Results
The full analysis set showed that the H. pylori eradication rates were 87.8% (252/287) and 82.52% (236/286) for the KEV and ESO groups, respectively (difference: 5.29%; 95% confidence interval [CI]: -0.55–11.18). Keverprazan was superior to esomeprazole in terms of eradication rate in the per protocol set (P=0.0382). The eradication rates for patients resistant or non-resistant to clarithromycin were both numerically higher in the KEV group than the ESO group (83.45% vs. 76.98% for clarithromycin-resistance; 92.31% vs. 88.16% for clarithromycin-non-resistance). The incidence of adverse events was similar in the KEV and ESO groups (76.31% vs. 77.62%), with most adverse events (>90%) being mild in severity. No TEAEs led to death in either group.
Conclusions
Keverprazan 20 mg twice daily, used as a component of bismuth quadruple therapy, provided effective H. pylori eradication and was non-inferior to an esomeprazole-based regimen.
{"title":"The efficacy of keverprazan-based quadruple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind, multicentre trial","authors":"Niandi Tan , Hao Wu , Cheng Lan , Chengxia Liu , Aijun Liao , Zhiyong Jiao , Dongxing Su , Xiaomei Zhang , Zhe Zhang , Weiming Xiao , Fangfang Li , Xing Li , Min Xia , Rongyuan Qiu , Huixin Chen , Youli Liu , Mei Su , Minhu Chen , Yinglian Xiao","doi":"10.1016/j.ijantimicag.2024.107320","DOIUrl":"10.1016/j.ijantimicag.2024.107320","url":null,"abstract":"<div><h3>Introduction</h3><div>Keverprazan is a novel potassium-competitive acid blocker. The advantages of keverprazan as a potent acid suppressor in <em>Helicobacter pylori</em> eradication have not yet been demonstrated. The aim of this study was to evaluate the efficacy of keverprazan as a component of bismuth quadruple therapy in <em>H. pylori</em> treatment.</div></div><div><h3>Methods</h3><div>Adult patients with <em>H. pylori</em> infection were enrolled and randomised to take keverprazan (KEV group)- or esomeprazole (ESO group)-quadruple therapy. The regimens contained keverprazan 20 mg or esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 240 mg and were administered twice daily for 14 days. The primary endpoint was the <em>H. pylori</em> eradication rate at 4 weeks after treatment.</div></div><div><h3>Results</h3><div>The full analysis set showed that the <em>H. pylori</em> eradication rates were 87.8% (252/287) and 82.52% (236/286) for the KEV and ESO groups, respectively (difference: 5.29%; 95% confidence interval [CI]: -0.55–11.18). Keverprazan was superior to esomeprazole in terms of eradication rate in the per protocol set (<em>P</em>=0.0382). The eradication rates for patients resistant or non-resistant to clarithromycin were both numerically higher in the KEV group than the ESO group (83.45% vs. 76.98% for clarithromycin-resistance; 92.31% vs. 88.16% for clarithromycin-non-resistance). The incidence of adverse events was similar in the KEV and ESO groups (76.31% vs. 77.62%), with most adverse events (>90%) being mild in severity. No TEAEs led to death in either group.</div></div><div><h3>Conclusions</h3><div>Keverprazan 20 mg twice daily, used as a component of bismuth quadruple therapy, provided effective <em>H. pylori</em> eradication and was non-inferior to an esomeprazole-based regimen.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107320"},"PeriodicalIF":4.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286367","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 : 2024-09-16DOI: 10.1016/j.ijantimicag.2024.107338
Xiang Geng , Yuxi Li , Ruochen Hao , Chunyan Xu , Zhun Li , Yajun Yang , Xiwang Liu , Jianyong Li , Wanxia Pu
Objective
Antibiotic resistance poses a considerable worldwide concern, particularly in clinical environments where drug-resistant Gram-negative bacteria like Klebsiella pneumoniae (K. pneumoniae) present a major challenge. The objective of this research was to investigate the mechanisms by which isobavachalcone (IBC) restores the sensitivity of K. pneumoniae to colistin in vitro and to validate the synergistic therapeutic effect in vivo.
Results
The results indicate that the combined administration of colistin and IBC exhibits a potent antibacterial effect both in vitro and in vivo. The in vitro concurrent administration of colistin and IBC resulted in increased membrane permeability, compromised cell integrity, diminished membrane fluidity, and disrupted membrane homeostasis. Additionally, this combination reduced biofilm production, inhibited the synthesis of the autoinducer factor, altered membrane potential, and affected levels of reactive oxygen species and adenosine triphosphate synthesis, ultimately leading to bacterial death. In vivo experiments on Galleria mellonella and mice demonstrated that the co-administration of colistin and IBC increased the survival rate and significantly reduced pathological damage compared to colistin alone.
Conclusion
These results suggested that IBC effectively restores the sensitivity of colistin by inducing physical disruption of bacterial membranes and oxidative stress. The combination therapy of colistin and IBC presents a viable and safe strategy to combat drug-resistant K. pneumoniae-associated infections.
{"title":"Isobavachalcone enhances sensitivity of colistin-resistant Klebsiella pneumoniae: In vitro and in vivo proof-of-concept studies","authors":"Xiang Geng , Yuxi Li , Ruochen Hao , Chunyan Xu , Zhun Li , Yajun Yang , Xiwang Liu , Jianyong Li , Wanxia Pu","doi":"10.1016/j.ijantimicag.2024.107338","DOIUrl":"10.1016/j.ijantimicag.2024.107338","url":null,"abstract":"<div><h3>Objective</h3><div>Antibiotic resistance poses a considerable worldwide concern, particularly in clinical environments where drug-resistant Gram-negative bacteria like <em>Klebsiella pneumoniae</em> (<em>K. pneumoniae</em>) present a major challenge. The objective of this research was to investigate the mechanisms by which isobavachalcone (IBC) restores the sensitivity of <em>K. pneumoniae</em> to colistin in vitro and to validate the synergistic therapeutic effect in vivo.</div></div><div><h3>Results</h3><div>The results indicate that the combined administration of colistin and IBC exhibits a potent antibacterial effect both in vitro and in vivo. The in vitro <em>c</em>oncurrent administration of colistin and IBC resulted in increased membrane permeability, compromised cell integrity, diminished membrane fluidity, and disrupted membrane homeostasis. Additionally, this combination reduced biofilm production, inhibited the synthesis of the autoinducer factor, altered membrane potential, and affected levels of reactive oxygen species and adenosine triphosphate synthesis, ultimately leading to bacterial death. In vivo experiments on <em>Galleria mellonella</em> and mice demonstrated that the co-administration of colistin and IBC increased the survival rate and significantly reduced pathological damage compared to colistin alone.</div></div><div><h3>Conclusion</h3><div>These results suggested that IBC effectively restores the sensitivity of colistin by inducing physical disruption of bacterial membranes and oxidative stress. The combination therapy of colistin and IBC presents a viable and safe strategy to combat drug-resistant <em>K. pneumoniae</em>-associated infections.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107338"},"PeriodicalIF":4.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1016/j.ijantimicag.2024.107337
Muchen Zhang , Siyuan Yang , Yongqing Liu , Zhiyu Zou , Yan Zhang , Yunrui Tian , Rong Zhang , Dejun Liu , Congming Wu , Jianzhong Shen , Huangwei Song , Yang Wang
The global increasing incidence of clinical infections caused by carbapenem-resistant Gram-negative pathogens requires urgent and effective treatment strategies. Antibiotic adjuvants represent a promising approach to enhance the efficacy of meropenem against carbapenem-resistant bacteria. This study shows that the anticancer agent 5-fluorouracil (5-FU, 50 µM) significantly reduced the minimum inhibitory concentration of meropenem against blaNDM-5 positive Escherichia coli by 32-fold through cell-based high-throughput screening. Further pharmacological studies indicated that 5-FU exhibited potentiation effects on carbapenem antibiotics against 42 Gram-negative bacteria producing either metallo-β-lactamases (MBLs), such as NDM and IMP, or serine β-lactamases (Ser-BLs), like KPC and OXA. These bacteria included E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp., 32 of which were obtained from human clinical samples. Mechanistic investigations revealed that 5-FU inhibited the transcription and expression of the blaNDM-5 gene. In addition, 5-FU combined with meropenem enhanced bacterial metabolism, and stimulated the production of reactive oxygen species (ROS), thereby rendering bacteria more susceptible to meropenem. In a mouse systemic infection model, 5-FU combined with meropenem reduced bacterial loads and effectively elevated the survival rate of 83.3%, compared with 16.7% with meropenem monotherapy. Collectively, these findings indicate the potential of 5-FU as a novel meropenem adjuvant to improve treatment outcomes against infections caused by carbapenem-resistant bacteria.
{"title":"Anticancer agent 5-fluorouracil reverses meropenem resistance in carbapenem-resistant Gram-negative pathogens","authors":"Muchen Zhang , Siyuan Yang , Yongqing Liu , Zhiyu Zou , Yan Zhang , Yunrui Tian , Rong Zhang , Dejun Liu , Congming Wu , Jianzhong Shen , Huangwei Song , Yang Wang","doi":"10.1016/j.ijantimicag.2024.107337","DOIUrl":"10.1016/j.ijantimicag.2024.107337","url":null,"abstract":"<div><div>The global increasing incidence of clinical infections caused by carbapenem-resistant Gram-negative pathogens requires urgent and effective treatment strategies. Antibiotic adjuvants represent a promising approach to enhance the efficacy of meropenem against carbapenem-resistant bacteria. This study shows that the anticancer agent 5-fluorouracil (5-FU, 50 µM) significantly reduced the minimum inhibitory concentration of meropenem against <em>bla</em><sub>NDM-5</sub> positive <em>Escherichia coli</em> by 32-fold through cell-based high-throughput screening. Further pharmacological studies indicated that 5-FU exhibited potentiation effects on carbapenem antibiotics against 42 Gram-negative bacteria producing either metallo-β-lactamases (MBLs), such as NDM and IMP, or serine β-lactamases (Ser-BLs), like KPC and OXA. These bacteria included <em>E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa</em> and <em>Acinetobacter spp.</em>, 32 of which were obtained from human clinical samples. Mechanistic investigations revealed that 5-FU inhibited the transcription and expression of the <em>bla</em><sub>NDM-5</sub> gene. In addition, 5-FU combined with meropenem enhanced bacterial metabolism, and stimulated the production of reactive oxygen species (ROS), thereby rendering bacteria more susceptible to meropenem. In a mouse systemic infection model, 5-FU combined with meropenem reduced bacterial loads and effectively elevated the survival rate of 83.3%, compared with 16.7% with meropenem monotherapy. Collectively, these findings indicate the potential of 5-FU as a novel meropenem adjuvant to improve treatment outcomes against infections caused by carbapenem-resistant bacteria.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107337"},"PeriodicalIF":4.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1016/j.ijantimicag.2024.107326
Xiaolan Huang , Xiaofen Liu , Yaxin Fan , Yu Wang , Beining Guo , Jingjing Wang , Jicheng Yu , Qiong Wei , Xiaojie Wu , Haihui Huang , Jing Zhang
Objective
Increasing antimicrobial resistance has led to the revival of the polymyxins as a last-resort therapeutic option for multidrug-resistant Gram-negative bacterial infections. A parenteral formulation of colistin sulfate is available solely in China. While the onset of action of IV colistin may occur faster than with its prodrug CMS, its pharmacokinetic (PK) profile remains unclear.
Methods
This single-centre, open-label, single- and multi-dose, phase 1 trial examined the PKs and safety of colistin sulfate in healthy Chinese adults. Participants received a single 10,000 units/kg (equivalent to 0.452 mg/kg) dose of colistin sulfate (single-dose group, n = 12) or the same dose q12h for 7 days (multi-dose group, n = 12) via a 2-h IV infusion. Colistin concentrations in plasma and urine were determined using LC-MS/MS, and the PK parameters calculated using non-compartmental analysis.
Results
After a single dose the peak concentration (Cmax), area under the curve from 0 to 12 h (AUC0-12h), terminal half-life (T1/2), volume of distribution (Vd), and total body clearance (CL) of colistin were 1.08 ± 0.18 mg/L, 4.73 ± 0.89 h·mg/L, 3.65 ± 0.55 h, 16.82 ± 2.70 L, and 3.24 ± 0.51 L/h, respectively. No accumulation of colistin was observed after multiple doses. The cumulative urinary recovery of colistin was 0.9 ± 0.7% within 24 h after multi-dose administration. No nephrotoxicity was reported.
Conclusions
This study is the first to report colistin PKs in healthy Chinese subjects after single and multiple doses of colistin sulfate. The PK and safety data are required for optimal dose selection in clinical practice.
{"title":"Pharmacokinetics and safety of colistin sulfate after single and multiple intravenous doses in healthy Chinese subjects","authors":"Xiaolan Huang , Xiaofen Liu , Yaxin Fan , Yu Wang , Beining Guo , Jingjing Wang , Jicheng Yu , Qiong Wei , Xiaojie Wu , Haihui Huang , Jing Zhang","doi":"10.1016/j.ijantimicag.2024.107326","DOIUrl":"10.1016/j.ijantimicag.2024.107326","url":null,"abstract":"<div><h3>Objective</h3><div>Increasing antimicrobial resistance has led to the revival of the polymyxins as a last-resort therapeutic option for multidrug-resistant Gram-negative bacterial infections. A parenteral formulation of colistin sulfate is available solely in China. While the onset of action of IV colistin may occur faster than with its prodrug CMS, its pharmacokinetic (PK) profile remains unclear.</div></div><div><h3>Methods</h3><div>This single-centre, open-label, single- and multi-dose, phase 1 trial examined the PKs and safety of colistin sulfate in healthy Chinese adults. Participants received a single 10,000 units/kg (equivalent to 0.452 mg/kg) dose of colistin sulfate (single-dose group, <em>n</em> = 12) or the same dose q12h for 7 days (multi-dose group, <em>n</em> = 12) via a 2-h IV infusion. Colistin concentrations in plasma and urine were determined using LC-MS/MS, and the PK parameters calculated using non-compartmental analysis.</div></div><div><h3>Results</h3><div>After a single dose the peak concentration (C<sub>max</sub>), area under the curve from 0 to 12 h (AUC<sub>0-12h</sub>), terminal half-life (T<sub>1/2</sub>), volume of distribution (V<sub>d</sub>), and total body clearance (CL) of colistin were 1.08 ± 0.18 mg/L, 4.73 ± 0.89 h·mg/L, 3.65 ± 0.55 h, 16.82 ± 2.70 L, and 3.24 ± 0.51 L/h, respectively. No accumulation of colistin was observed after multiple doses. The cumulative urinary recovery of colistin was 0.9 ± 0.7% within 24 h after multi-dose administration. No nephrotoxicity was reported.</div></div><div><h3>Conclusions</h3><div>This study is the first to report colistin PKs in healthy Chinese subjects after single and multiple doses of colistin sulfate. The PK and safety data are required for optimal dose selection in clinical practice.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107326"},"PeriodicalIF":4.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07DOI: 10.1016/j.ijantimicag.2024.107332
Jack Chang , Gwendolyn M. Pais , Erin F. Barreto , Bryce Young , Haley Scott , Zachary Schwartz , Collin Cartwright , Raymond Jubrail , Anand Srivastava , Marc H. Scheetz
Routinely used kidney biomarkers of injury and function such as serum creatinine and urine albumin to creatinine ratio, are neither sensitive nor specific. Future biomarkers are being developed for clinical use and have already been included in guidance from groups such as the U.S. Food and Drug Administration and the Predictive Safety Testing Consortium. These biomarkers have important implications for early identification of kidney injury and more accurate measurement of kidney function. Many antibiotics are either eliminated by the kidney or can cause clinically significant nephrotoxicity. As a result, clinicians should be familiar with new biomarkers of kidney function and injury, their place in clinical practice, and applications for antibiotic dosing.
{"title":"Past, Present, and Future Biomarkers of Kidney Function and Injury: The Relationship With Antibiotics","authors":"Jack Chang , Gwendolyn M. Pais , Erin F. Barreto , Bryce Young , Haley Scott , Zachary Schwartz , Collin Cartwright , Raymond Jubrail , Anand Srivastava , Marc H. Scheetz","doi":"10.1016/j.ijantimicag.2024.107332","DOIUrl":"10.1016/j.ijantimicag.2024.107332","url":null,"abstract":"<div><div>Routinely used kidney biomarkers of injury and function such as serum creatinine and urine albumin to creatinine ratio, are neither sensitive nor specific. Future biomarkers are being developed for clinical use and have already been included in guidance from groups such as the U.S. Food and Drug Administration and the Predictive Safety Testing Consortium. These biomarkers have important implications for early identification of kidney injury and more accurate measurement of kidney function. Many antibiotics are either eliminated by the kidney or can cause clinically significant nephrotoxicity. As a result, clinicians should be familiar with new biomarkers of kidney function and injury, their place in clinical practice, and applications for antibiotic dosing.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107332"},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07DOI: 10.1016/j.ijantimicag.2024.107327
Feilong Zhang , Zhihua Li , Xinmeng Liu , Ziyao Li , Zichen Lei , Jiankang Zhao , Yulin Zhang , Yongli Wu , Xinrui Yang , Binghuai Lu
Objectives
The aim of this study was to investigate interspecies transfer of resistance gene blaNDM-1 and intraspecies transfer of resistance gene blaKPC-2 in Serratia marcescens, and explore the epidemical and evolutionary characteristics of carbapenemase-producing S. marcescens (CPSM) regionally and globally.
Methods
Interspecies and intraspecies transfer of blaKPC-2- or blaNDM-1 were identified by antimicrobial susceptibility testing, plasmid conjugation and curing, discovery of transposable units (TUs), outer membrane vesicles (OMVs), qPCR, whole-genome sequencing (WGS) and bioinformatic analysis. The genomic evolution of CPSM strains was explored by cgSNP and maximum-likelihood phylogenetic tree.
Results
CPSM S50079 strain, co-carrying blaKPC-2 and blaNDM-1 on one plasmid, was isolated from the blood of a patient with acute pancreatitis and could generate TUs carrying either blaKPC-2 or blaNDM-1. The interspecies transfer of blaNDM-1-carrying plasmid from Providencia rettgeri P50213, producing the identical blaNDM-1-carrying TUs, to S. marcescens S50079K, an S50079 variant via plasmid curing, was identified through blaNDM-1-harbouring plasmid conjugation and OMVs transfer. Moreover, the intraspecies transfer of blaKPC-2, mediated by IS26 from plasmid to chromosome in S50079, was also identified. In another patient, who underwent lung transplantation, interspecies transfer of blaNDM-1 carried by IncX3 plasmid was identified among S. marcescens and Citrobacter freundii as well as Enterobacter hormaechei via plasmid transfer. Furthermore, 11 CPSM from 349 non-repetitive S. marcescens strains were identified in the same hospital, and clonal dissemination, with carbapenemase evolution from blaKPC-2 to both blaKPC-2 and blaNDM-1, was found in the 8 CPSM across 4 years. Finally, the analysis of 236 global CPSM from 835 non-repetitive S. marcescens genomes, retrieved from the NCBI database, revealed long-term spread and evolution worldwide, and would cause the convergence of more carbapenemase genes.
Conclusions
Interspecies transfer of resistance gene blaNDM-1 and intraspecies transfer of resistance gene blaKPC-2 in CPSM were identified. Nosocomial and global dissemination of CPSM were revealed and more urgent surveillance was acquired.
{"title":"In-host intra- and inter-species transfer of blaKPC-2 and blaNDM-1 in Serratia marcescens and its local and global epidemiology","authors":"Feilong Zhang , Zhihua Li , Xinmeng Liu , Ziyao Li , Zichen Lei , Jiankang Zhao , Yulin Zhang , Yongli Wu , Xinrui Yang , Binghuai Lu","doi":"10.1016/j.ijantimicag.2024.107327","DOIUrl":"10.1016/j.ijantimicag.2024.107327","url":null,"abstract":"<div><h3>Objectives</h3><div>The aim of this study was to investigate interspecies transfer of resistance gene <em>bla</em><sub>NDM-1</sub> and intraspecies transfer of resistance gene <em>bla</em><sub>KPC-2</sub> in <em>Serratia marcescens</em>, and explore the epidemical and evolutionary characteristics of carbapenemase-producing <em>S. marcescens</em> (CPSM) regionally and globally.</div></div><div><h3>Methods</h3><div>Interspecies and intraspecies transfer of <em>bla</em><sub>KPC-2</sub>- or <em>bla</em><sub>NDM-1</sub> were identified by antimicrobial susceptibility testing, plasmid conjugation and curing, discovery of transposable units (TUs), outer membrane vesicles (OMVs), qPCR, whole-genome sequencing (WGS) and bioinformatic analysis. The genomic evolution of CPSM strains was explored by cgSNP and maximum-likelihood phylogenetic tree.</div></div><div><h3>Results</h3><div>CPSM S50079 strain, co-carrying <em>bla</em><sub>KPC-2</sub> and <em>bla</em><sub>NDM-1</sub> on one plasmid, was isolated from the blood of a patient with acute pancreatitis and could generate TUs carrying either <em>bla</em><sub>KPC-2</sub> or <em>bla</em><sub>NDM-1</sub>. The interspecies transfer of <em>bla</em><sub>NDM-1</sub>-carrying plasmid from <em>Providencia rettgeri</em> P50213, producing the identical <em>bla</em><sub>NDM-1</sub>-carrying TUs, to <em>S. marcescens</em> S50079K, an S50079 variant <em>via</em> plasmid curing, was identified through <em>bla</em><sub>NDM-1</sub>-harbouring plasmid conjugation and OMVs transfer. Moreover, the intraspecies transfer of <em>bla</em><sub>KPC-2</sub>, mediated by IS<em>26</em> from plasmid to chromosome in S50079, was also identified. In another patient, who underwent lung transplantation, interspecies transfer of <em>bla</em><sub>NDM-1</sub> carried by IncX3 plasmid was identified among <em>S. marcescens</em> and <em>Citrobacter freundii</em> as well as <em>Enterobacter hormaechei via</em> plasmid transfer. Furthermore, 11 CPSM from 349 non-repetitive <em>S. marcescens</em> strains were identified in the same hospital, and clonal dissemination, with carbapenemase evolution from <em>bla</em><sub>KPC-2</sub> to both <em>bla</em><sub>KPC-2</sub> and <em>bla</em><sub>NDM-1</sub>, was found in the 8 CPSM across 4 years. Finally, the analysis of 236 global CPSM from 835 non-repetitive <em>S. marcescens</em> genomes, retrieved from the NCBI database, revealed long-term spread and evolution worldwide, and would cause the convergence of more carbapenemase genes.</div></div><div><h3>Conclusions</h3><div>Interspecies transfer of resistance gene <em>bla</em><sub>NDM-1</sub> and intraspecies transfer of resistance gene <em>bla</em><sub>KPC-2</sub> in CPSM were identified. Nosocomial and global dissemination of CPSM were revealed and more urgent surveillance was acquired.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107327"},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07DOI: 10.1016/j.ijantimicag.2024.107331
Ju Zhang , Huan Zhang , Xiao-Jing Zhu , Nuo Yao , Ju-Mei Yin , Jian Liu , Han-Jun Dan , Qi-Meng Pang , Zhi-Hua Liu , Yong-Quan Shi
Background
Vonoprazan is a new acid-suppressing drug that provides an additional choice for eradicating Helicobacter pylori. The effectiveness and safety of vonoprazan and high-dose amoxicillin (VHA) dual therapy requires study in a systematic analysis.
Materials and Methods
A comprehensive search of the literature from the PubMed, Embase, Cochrane Library, and Web of Science databases was conducted up to 16 May 2024. Trials comparing H. pylori eradication rates, adverse events, and compliance of VHA dual therapy with that of other therapies were included. RevMan 5.4 was used for statistical analysis.
Results
Eleven randomised controlled trials (RCTs) and two retrospective clinical studies with 4570 samples were included. VHA dual therapy had superior H. pylori eradication rates (intention-to-treat [ITT]: 86.0% vs. 80.7%; odds ratio [OR]=1.36; 95% confidence interval [CI] 1.07–1.73; P=0.01; per-protocol [PP]: 90.6% vs. 85.7%; OR=1.42; 95% CI 1.07–1.88; P=0.02), fewer adverse events (15.4% vs. 27.7%; OR=0.49; 95% CI 0.35–0.68, P<0.0001), and similar compliance (94.6% vs. 93.2%; OR=1.27; 95% CI 0.98–1.64; P=0.07) compared with other guideline therapies. According to subgroup analysis with PP data, VHA dual therapy is more effective than bismuth quadruple therapy based on proton-pump inhibitors (P-BQT) (93.5% vs. 89.3%; OR=1.76; 95% CI 1.03–3.00; P=0.04). In addition, the eradication rates for 7-day, 10-day and 14-day VHA dual therapy were 65% (95% CI 0.55–0.75), 92% (95% CI 0.91–0.94) and 93% (95% CI 0.90–0.97), respectively.
Conclusion
VHA dual therapy for 10 or 14 days showed superior efficacy and safety compared with therapies recommended by the guidelines and should be prioritised for adoption.
背景:新型抑酸药物沃诺普拉赞为根除幽门螺杆菌提供了更多选择。因此,沃诺普拉赞和大剂量阿莫西林双重疗法是否更有效、更安全,需要进行系统分析:对截至 2024 年 5 月 16 日的 PubMed、Embase、Cochrane Library 和 Web of Science 数据库中的文献进行了全面检索。纳入了评估VHA双重疗法与其他疗法相比的幽门螺杆菌根除率、不良事件和依从性的研究。使用RevMan 5.4进行统计分析:结果:共纳入11项研究性临床试验和2项回顾性临床研究,4570个样本。VHA双重疗法具有更高的幽门螺杆菌根除率(ITT:86.0% vs 80.7%,OR=1.36,95%CI 1.07-1.73,P=0.01;PP:90.6% vs 85.7%,OR=1.42,95%CI 1.07-1.88,P=0.02)、更少的不良反应(15.4% vs 27.7%,OR=0.49,95%CI 0.35-0.68,PConclusion):与指南推荐的疗法相比,VHA 10 天或 14 天双重疗法的疗效和安全性更佳,应优先采用。
{"title":"Efficacy and safety of vonoprazan and high-dose amoxicillin dual therapy in eradicating Helicobacter pylori: A systematic review and meta-analysis","authors":"Ju Zhang , Huan Zhang , Xiao-Jing Zhu , Nuo Yao , Ju-Mei Yin , Jian Liu , Han-Jun Dan , Qi-Meng Pang , Zhi-Hua Liu , Yong-Quan Shi","doi":"10.1016/j.ijantimicag.2024.107331","DOIUrl":"10.1016/j.ijantimicag.2024.107331","url":null,"abstract":"<div><h3>Background</h3><div>Vonoprazan is a new acid-suppressing drug that provides an additional choice for eradicating <em>Helicobacter pylori</em>. The effectiveness and safety of vonoprazan and high-dose amoxicillin (VHA) dual therapy requires study in a systematic analysis.</div></div><div><h3>Materials and Methods</h3><div>A comprehensive search of the literature from the PubMed, Embase, Cochrane Library, and Web of Science databases was conducted up to 16 May 2024. Trials comparing <em>H. pylori</em> eradication rates, adverse events, and compliance of VHA dual therapy with that of other therapies were included. RevMan 5.4 was used for statistical analysis.</div></div><div><h3>Results</h3><div>Eleven randomised controlled trials (RCTs) and two retrospective clinical studies with 4570 samples were included. VHA dual therapy had superior <em>H. pylori</em> eradication rates (intention-to-treat [ITT]: 86.0% vs. 80.7%; odds ratio [OR]=1.36; 95% confidence interval [CI] 1.07–1.73; <em>P</em>=0.01; per-protocol [PP]: 90.6% vs. 85.7%; OR=1.42; 95% CI 1.07–1.88; <em>P</em>=0.02), fewer adverse events (15.4% vs. 27.7%; OR=0.49; 95% CI 0.35–0.68, <em>P</em><0.0001), and similar compliance (94.6% vs. 93.2%; OR=1.27; 95% CI 0.98–1.64; <em>P</em>=0.07) compared with other guideline therapies. According to subgroup analysis with PP data, VHA dual therapy is more effective than bismuth quadruple therapy based on proton-pump inhibitors (P-BQT) (93.5% vs. 89.3%; OR=1.76; 95% CI 1.03–3.00; <em>P</em>=0.04). In addition, the eradication rates for 7-day, 10-day and 14-day VHA dual therapy were 65% (95% CI 0.55–0.75), 92% (95% CI 0.91–0.94) and 93% (95% CI 0.90–0.97), respectively.</div></div><div><h3>Conclusion</h3><div>VHA dual therapy for 10 or 14 days showed superior efficacy and safety compared with therapies recommended by the guidelines and should be prioritised for adoption.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107331"},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286361","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 : 2024-09-07DOI: 10.1016/j.ijantimicag.2024.107333
Baran Alkan , M. Asli Tuncer , A. Çağkan İnkaya
Polyomaviruses are a group of small, non-enveloped, double-stranded DNA viruses that can infect various hosts, including humans. BKPyV causes conditions such as human polyomavirus-associated nephropathy (HPyVAN), human polyomavirus-associated haemorrhagic cystitis (HPyVHC), and human polyomavirus-associated urothelial cancer (HPyVUC). JC polyomavirus (JCPyV), on the other hand, is the causative agent of progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system. PML primarily affects immunocompromised individuals, including those with HIV, recipients of certain immunosuppressive therapies, and transplant patients. The treatment options for HPyV infections have been limited, but recent developments in virus-specific T cell (VST) therapy have shown promise. Although VST therapy has shown potential in treating both BKPyV and JCPyV infections, several challenges remain. These include the time-consuming and costly preparation of VSTs, the need for sophisticated production facilities, and uncertainties regarding the optimal cell type and infusion frequency. To the best of our knowledge, 85 patients with haemorrhagic cystitis, 27 patients with BKPyV viremia, 2 patients with BKPyV nephritis, 14 patients with haemorrhagic cystitis and BKPyV viremia, and 32 patients with PML have been treated with VST in the literature. The overall response results were 82 complete response, 33 partial response, 35 no response, and 10 no-outcome-reported. This review underscores the importance of VST therapy as a promising treatment approach for polyomavirus infections, emphasising the need for continued research and clinical trials to refine and expand this innovative immunotherapeutic strategy.
{"title":"Advances in Virus-Specific T-Cell Therapy for Polyomavirus Infections: A Comprehensive Review","authors":"Baran Alkan , M. Asli Tuncer , A. Çağkan İnkaya","doi":"10.1016/j.ijantimicag.2024.107333","DOIUrl":"10.1016/j.ijantimicag.2024.107333","url":null,"abstract":"<div><div>Polyomaviruses are a group of small, non-enveloped, double-stranded DNA viruses that can infect various hosts, including humans. BKPyV causes conditions such as human polyomavirus-associated nephropathy (HPyVAN), human polyomavirus-associated haemorrhagic cystitis (HPyVHC), and human polyomavirus-associated urothelial cancer (HPyVUC). JC polyomavirus (JCPyV), on the other hand, is the causative agent of progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system. PML primarily affects immunocompromised individuals, including those with HIV, recipients of certain immunosuppressive therapies, and transplant patients. The treatment options for HPyV infections have been limited, but recent developments in virus-specific T cell (VST) therapy have shown promise. Although VST therapy has shown potential in treating both BKPyV and JCPyV infections, several challenges remain. These include the time-consuming and costly preparation of VSTs, the need for sophisticated production facilities, and uncertainties regarding the optimal cell type and infusion frequency. To the best of our knowledge, 85 patients with haemorrhagic cystitis, 27 patients with BKPyV viremia, 2 patients with BKPyV nephritis, 14 patients with haemorrhagic cystitis and BKPyV viremia, and 32 patients with PML have been treated with VST in the literature. The overall response results were 82 complete response, 33 partial response, 35 no response, and 10 no-outcome-reported. This review underscores the importance of VST therapy as a promising treatment approach for polyomavirus infections, emphasising the need for continued research and clinical trials to refine and expand this innovative immunotherapeutic strategy.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107333"},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07DOI: 10.1016/j.ijantimicag.2024.107335
Yuhan Wei , Huijuan Luo , Xia Chen , Qun Yan
Background
This study aimed to assess the incidence and risk factors of subsequent carbapenem-resistant Enterobacterales (CRE) infection among rectal carriers, and their association with geographic region and age.
Methods
A meta-analysis of studies investigating incidence and/or risk factors of subsequent CRE infection among rectal carriers was conducted, with subgroup analyses by geographic region and age. PubMed, Embase, Web of Science, and Cochrane Library were searched (published from inception to 31 January 2024). This study is registered with PROSPERO (CRD42023444420).
Results
Of 4459 studies identified, 24 studies with 8188 CRE rectal carriers were included. The pooled incidence of subsequent CRE infection was 20.6% (95% CI 15.9–25.8). The highest incidence was seen in America (23.6%, 95% CI 14.2–34.5), followed by Europe (20.9%, 95% CI 12.5–30.8) and Asia (19.8%, 95% CI 12.7–27.9). Children had a greater incidence (26.7%, 95% CI 21.3–32.3) than adults (19.8%, 95% CI 14.9–25.2). Fourteen factors were associated with subsequent CRE infection. In Asia, the most notable risk factor was gastritis (odds ratio [OR] 4.95 95% CI 1.87–13.11). In Europe, admission to the intensive care unit was prominent (OR 2.76 95% CI 1.14–6.65). In the America, the use of a urinary Foley catheter (OR 4.33 95% CI 1.06-17.70) was dominant. Admission to the intensive care unit was most notable in adults (OR 3.01 95% CI 1.80–5.02), while mechanical ventilation was shown the greatest significance in children (OR 15.61 95% CI 4.39–55.47).
Conclusions
Risk of subsequent CRE infection among rectal carriers was critical. Identifying the risk factors for subsequent infection could help in developing more potent prevention and control measures to reduce CRE infection.
研究目的本研究旨在评估直肠带菌者继发 CRE 感染的发生率和风险因素,以及它们与地理区域和年龄的关系:对调查直肠带菌者CRE后续感染发生率和/或风险因素的研究进行了荟萃分析,并按地理区域和年龄进行了亚组分析。研究人员检索了 PubMed、Embase、Web of Science 和 Cochrane Library(发表时间从开始到 2024 年 1 月 31 日)。本研究已在 PROSPERO 注册,编号为 CRD42023444420:结果:在确定的 4459 项研究中,纳入了 24 项研究,共有 8188 名 CRE 直肠携带者。CRE后续感染的总发生率为20.6%(95% CI 15.9-25.8)。美国的发病率最高(23.6%,95% CI 14.2-34.5),其次是欧洲(20.9%,95% CI 12.5-30.8)和亚洲(19.8%,95% CI 12.7-27.9)。儿童的发病率(26.7%,95% CI 21.3-32.3)高于成人(19.8%,95% CI 14.9-25.2)。有 14 个因素与随后的 CRE 感染有关。在亚洲,最显著的风险因素是胃炎(OR 4.95 95% CI 1.87-13.11)。在欧洲,入住重症监护室是最重要的因素(OR 2.76 95% CI 1.14-6.65)。在美国,使用输尿导管(OR 4.33 95% CI 1.06-17.70)是主要原因。入住重症监护室在成人中最显著(OR 3.01 95% CI 1.80-5.02),而机械通气在儿童中最显著(OR 15.61 95% CI 4.39-55.47):结论:直肠带菌者继发 CRE 感染的风险至关重要。结论:直肠携带者继发 CRE 感染的风险至关重要,确定继发感染的风险因素有助于制定更有效的预防和控制措施,减少 CRE 感染。
{"title":"Epidemiology of Subsequent Carbapenem-Resistant Enterobacterales (CRE) Infection Among Rectal Carriers: A Meta-Analysis of Incidence, Risk Factors and Their Association With Geographic Region and Age","authors":"Yuhan Wei , Huijuan Luo , Xia Chen , Qun Yan","doi":"10.1016/j.ijantimicag.2024.107335","DOIUrl":"10.1016/j.ijantimicag.2024.107335","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to assess the incidence and risk factors of subsequent carbapenem-resistant Enterobacterales (CRE) infection among rectal carriers, and their association with geographic region and age.</div></div><div><h3>Methods</h3><div>A meta-analysis of studies investigating incidence and/or risk factors of subsequent CRE infection among rectal carriers was conducted, with subgroup analyses by geographic region and age. PubMed, Embase, Web of Science, and Cochrane Library were searched (published from inception to 31 January 2024). This study is registered with PROSPERO (CRD42023444420).</div></div><div><h3>Results</h3><div>Of 4459 studies identified, 24 studies with 8188 CRE rectal carriers were included. The pooled incidence of subsequent CRE infection was 20.6% (95% CI 15.9–25.8). The highest incidence was seen in America (23.6%, 95% CI 14.2–34.5), followed by Europe (20.9%, 95% CI 12.5–30.8) and Asia (19.8%, 95% CI 12.7–27.9). Children had a greater incidence (26.7%, 95% CI 21.3–32.3) than adults (19.8%, 95% CI 14.9–25.2). Fourteen factors were associated with subsequent CRE infection. In Asia, the most notable risk factor was gastritis (odds ratio [OR] 4.95 95% CI 1.87–13.11). In Europe, admission to the intensive care unit was prominent (OR 2.76 95% CI 1.14–6.65). In the America, the use of a urinary Foley catheter (OR 4.33 95% CI 1.06-17.70) was dominant. Admission to the intensive care unit was most notable in adults (OR 3.01 95% CI 1.80–5.02), while mechanical ventilation was shown the greatest significance in children (OR 15.61 95% CI 4.39–55.47).</div></div><div><h3>Conclusions</h3><div>Risk of subsequent CRE infection among rectal carriers was critical. Identifying the risk factors for subsequent infection could help in developing more potent prevention and control measures to reduce CRE infection.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107335"},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}