International Journal of Antimicrobial Agents最新文献

{"title":"Conversion of blaKPC-2 to blaKPC-33 leads to worldwide emergence of ceftazidime-avibactam resistance in Klebsiella pneumoniae","authors":"","doi":"10.1016/j.ijantimicag.2024.107342","DOIUrl":"10.1016/j.ijantimicag.2024.107342","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346169","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}

{"title":"No resistance development against corallopyronin A in Wolbachia in C6/36 cell culture","authors":"","doi":"10.1016/j.ijantimicag.2024.107344","DOIUrl":"10.1016/j.ijantimicag.2024.107344","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346171","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}

{"title":"Effectiveness of combination therapy with intrathecal or intraventricular administration of polymyxin B for hospital-acquired central nervous system infections caused by carbapenem-resistant Acinetobacter baumannii: A retrospective study","authors":"","doi":"10.1016/j.ijantimicag.2024.107334","DOIUrl":"10.1016/j.ijantimicag.2024.107334","url":null,"abstract":"<div><h3>Objectives</h3><div>To evaluate the therapeutic regimen, efficacy and safety of intrathecal or intraventricular (ITH/IVT) administration of polymyxin B for hospital-acquired central nervous system (CNS) infections caused by carbapenem-resistant <em>Acinetobacter baumannii</em> (CRAB).</div></div><div><h3>Methods</h3><div>A retrospective study was undertaken of patients with CNS infections caused by CRAB treated with ITH/IVT combination therapy. The primary outcome was the clinical efficacy of treatment. The secondary outcomes were the bacterial clearance rate and the safety of therapy.</div></div><div><h3>Results</h3><div>In total, 35 patients who received ITH [<em>n</em>=13 (37.1%)] or IVT [<em>n</em>=22 (62.9%)] polymyxin B as combination therapy were included in this study. The median duration of ITH/IVT polymyxin B therapy was 9 (interquartile range 7–11) days. The overall clinical cure rate and bacterial clearance rate were 77.1% and 85.7%, respectively. No adverse effects considered to be related to ITH/IVT polymyxin B were recorded. Clinical failure was independently associated with an Acute Physiology and Chronic Health Evaluation II score ≥15 [odds ratio (OR) 1.24, 95% confidence interval (CI) 1.05–1.42; <em>P</em>=0.038] and a Glasgow Coma Scale score ≤8 (OR 0.69, 95% CI 0.49–0.88; <em>P</em>=0.029). Early administration (≤4 days of infection onset) of ITH/IVT polymyxin B therapy resulted in a significantly higher clinical cure rate (OR 0.65, 95% CI 0.49–1.12; <em>P</em>&lt;0.001), and may reduce the length of treatment and adverse effects.</div></div><div><h3>Conclusions</h3><div>ITH/IVT administration of polymyxin B is a valid alternative for the treatment of CNS infections caused by CRAB. Early use of ITH/IVT polymyxin B can result in greater clinical success.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307726","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}

{"title":"International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page","authors":"","doi":"10.1016/j.ijantimicag.2024.107336","DOIUrl":"10.1016/j.ijantimicag.2024.107336","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0924857924002528/pdfft?md5=adc7750783167a763dc11fc97bf0372b&pid=1-s2.0-S0924857924002528-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142243398","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}

{"title":"Impact of nitric oxide donors on capsule, biofilm and resistance profiles of Klebsiella pneumoniae","authors":"","doi":"10.1016/j.ijantimicag.2024.107339","DOIUrl":"10.1016/j.ijantimicag.2024.107339","url":null,"abstract":"<div><div><em>Klebsiella pneumoniae</em> is considered to be a critical public health threat due to its ability to cause fatal, multi-drug-resistant infections in the bloodstream and key organs. The polysaccharide-based capsule layer that shields <em>K. pneumoniae</em> from clearance via innate immunity is a prominent virulence factor. <em>K. pneumoniae</em> also forms biofilms on biotic and abiotic surfaces. These biofilms significantly reduce penetration by, and antibacterial activity from, traditional antibiotics. Nitric oxide (NO), an endogenous molecule involved in the innate immune system, is equally effective at eradicating bacteria but without engendering resistance. This study investigated the effects of NO-releasing small molecules capable of diverse release kinetics on the capsule and biofilm formation characteristics of multiple <em>K. pneumoniae</em> strains. The use of NO donors with moderate and extended NO-release properties (i.e., half-life &gt;1.8 h) inhibited bacterial growth. Additionally, treatment with NO decreased capsule mucoviscosity in <em>K. pneumoniae</em> strains that normally exhibit hypermucoviscosity. The NO donors were also effective against <em>K. pneumoniae</em> biofilms at the same minimum biocidal concentrations that eliminated planktonic bacteria, while meropenem showed little antibacterial action in the same experiments. These results represent the first account of exogenous NO affecting biomarkers involved in <em>K. pneumoniae</em> infections, and may therefore inform future development of NO-based therapeutics for treating such infections.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286362","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}

{"title":"In-vitro activities of essential antimicrobial agents including aztreonam/avibactam, eravacycline, colistin and other comparators against carbapenem-resistant bacteria with different carbapenemase genes: A multi-centre study in China, 2021","authors":"","doi":"10.1016/j.ijantimicag.2024.107341","DOIUrl":"10.1016/j.ijantimicag.2024.107341","url":null,"abstract":"<div><h3>Objective</h3><div>Carbapenem-resistant bacteria (CRB), including carbapenem-resistant <em>Acinetobacter baumannii</em> (CRAB), carbapenem-resistant <em>Pseudomonas aeruginosa</em> (CRPA) and carbapenem-resistant Enterobacterales (CRE), pose a considerable threat to public health in China. Eravacycline, aztreonam/avibactam and colistin are important antimicrobial agents for the treatment of serious infections caused by CRB. This study aimed to evaluate the prevalence of CRB strains, and the susceptibility of commonly used clinical antimicrobial agents against strains with different carbapenemase genes.</div></div><div><h3>Methods</h3><div>In total, 7194 gram-negative bacteria strains were collected from different regions of China, and 924 carbapenem-resistant strains were identified. All strains were from confirmed infections. Antimicrobial susceptibility testing, covering 21 antimicrobial agents including aztreonam/avibactam, eravacycline, colistin and other comparators, was performed using the broth microdilution method. Carbapenemase genes (<em>bla</em>_KPC, <em>bla</em>_NDM, <em>bla</em>_OXA, <em>bla</em>_IMP and <em>bla</em>_VIM) were screened using polymerase chain reaction amplification and sequence analysis. All statistical analyses were performed using Statistical Package for the Social Sciences Version 23.0.</div></div><div><h3>Results</h3><div>The isolation rates of CRE, CRAB and CRPA were 6.31% (332/5265), 62.95% (440/699) and 15.20% (152/1000), respectively. The predominant carbapenemase in carbapenem-resistant <em>Escherichia coli</em> (CRECO) was NDM, while in carbapenem-resistant <em>Klebsiella pneumoniae</em> (CRKP), it was KPC. All CRAB produced OXA-23, and 85.52% of CRPA did not produce any of the following carbapenemases: NDM, KPC, VIM, IMP and OXA. Aztreonam/avibactam, colistin and eravacycline exhibited high antimicrobial activity against different species producing various carbapenemases. Compared with ceftazidime/avibactam, aztreonam/avibactam demonstrated superior antimicrobial activity, particularly pronounced in CRECO and strains producing metallo-beta-lactamases. In comparisons between tigecycline and eravacycline, the latter maintained higher antimicrobial activity across different species. Antimicrobial agents exhibited varying levels of activity against strains with different resistance mechanisms.</div></div><div><h3>Conclusions</h3><div>Using aztreonam/avibactam, eravacycline and colistin to treat infections caused by CRB offers significant advantages. These findings will guide clinical practice and optimize antimicrobial administration.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286363","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}

{"title":"N-acetylcysteine effects on extracellular polymeric substances of Xylella fastidiosa: A spatiotemporal investigation with implications for biofilm disruption","authors":"","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":null,"pages":null},"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}

{"title":"The efficacy of keverprazan-based quadruple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind, multicentre trial","authors":"","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 (&gt;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":null,"pages":null},"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}

{"title":"Isobavachalcone enhances sensitivity of colistin-resistant Klebsiella pneumoniae: In vitro and in vivo proof-of-concept studies","authors":"","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":null,"pages":null},"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}

{"title":"Anticancer agent 5-fluorouracil reverses meropenem resistance in carbapenem-resistant Gram-negative pathogens","authors":"","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>_NDM-5 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>_NDM-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.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"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}