International Journal of Antimicrobial Agents最新文献

{"title":"Co-adjuvanting Nod2-stimulating bacteria with a TLR7 agonist elicits potent protective immunity against respiratory virus infection","authors":"Sujin An ,&nbsp;Jeein Oh ,&nbsp;Hoh-Jeong Shon ,&nbsp;Jaehwan Song ,&nbsp;Youn Soo Choi ,&nbsp;Donghyun Kim","doi":"10.1016/j.ijantimicag.2024.107369","DOIUrl":"10.1016/j.ijantimicag.2024.107369","url":null,"abstract":"<div><h3>Objectives</h3><div>This study investigates the synergistic effect of combining the TLR7 agonist Imiquimod with either the Nod2 agonist (muramyl dipeptide; MDP) or commensal bacteria as nasal vaccine adjuvants to enhance immunity against respiratory viruses.</div></div><div><h3>Methods</h3><div>Mice assessed immune responses, including antibody and cytokine profiles, after intranasal immunization with antigen and adjuvant combinations. BMDCs were cultured with these components to measure cytokine production. Germinal center formation and hapten-specific antibodies were evaluated using OT-II T-cell transfer and hapten-ovalbumin. Commensal bacteria from healthy nasal cavities were screened for Nod2-stimulating activity using a reporter assay. Protective efficacy against viral pathogens was evaluated using an influenza A infection model and a pseudovirus system for SARS-CoV-2 neutralizing antibodies.</div></div><div><h3>Results</h3><div>Screening identified Imiquimod as a potent enhancer of adaptive immune responses during nasal immunization, showing synergy with MDP. This combination elevated IL-12p40 and IL-6 levels, enhanced antibody production, and promoted T follicular helper cell differentiation. The Imiquimod-MDP combination provided robust protection against influenza and SARS-CoV-2. Screening of commensal bacteria revealed differential Nod2-stimulating capacities, with <em>Staphylococcus aureus</em> exhibiting superior synergy with Imiquimod compared to <em>Staphylococcus epidermidis</em>. Notably, this synergism was abolished in Nod2-deficient mice, and pretreatment with <em>S. aureus</em> significantly enhanced the protective efficacy of Imiquimod against influenza compared to <em>S. epidermidis</em>.</div></div><div><h3>Conclusions</h3><div>Combining Imiquimod with MDP or high Nod2-stimulating bacteria offers a promising strategy for nasal vaccine adjuvants. These combinations effectively boost humoral and cellular immune responses, providing strong protection against respiratory viruses.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107369"},"PeriodicalIF":4.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545313","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":"Acetylshikonin reduces the spread of antibiotic resistance via plasmid conjugation","authors":"Wei Liu ,&nbsp;Zhiqiang wang ,&nbsp;Yanhu Huang ,&nbsp;Yuan Liu ,&nbsp;Ruichao Li ,&nbsp;Mianzhi Wang ,&nbsp;Haijie Zhang ,&nbsp;Chuang Meng ,&nbsp;Xia Xiao","doi":"10.1016/j.ijantimicag.2024.107370","DOIUrl":"10.1016/j.ijantimicag.2024.107370","url":null,"abstract":"<div><div>The plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs) stands out as the primary driver behind the dissemination of antimicrobial resistance (AMR). Developing effective inhibitors that target conjugative transfer represents an potential strategy for addressing the issue of AMR. Here, we studied the effect of acetylshikonin (ASK), a botanical derivative, on plasmid conjugation. The conjugative transfer of RP4-7 plasmid inter and intra species was notably reduced by ASK. The conjugation process of IncI2 and IncX4 plasmids harbouring the mobile colistin resistance gene (<em>mcr</em>-1), IncX4 and IncX3 plasmids containing the carbapenem resistance gene (<em>bla</em>_NDM-5), and IncFI and IncFII plasmids possessing the tetracycline resistance gene [<em>tet</em>(X4)] were also reduced by ASK. Importantly, the conjugative transfer frequency of <em>mcr</em>-1 positive IncI2 plasmid in mouse peritoneal conjugation model and gut conjugation model was reduced by ASK. The mechanism investigation showed that ASK disrupted the functionality of the bacterial cell membrane. Furthermore, the proton motive force (PMF) was dissipated. In addition, ASK blocked the electron transmission in bacteria's electron transport chain (ETC) through disturbing the quinone interaction, resulting in an insufficient energy supply for conjugation. Collectively, ASK is a potential conjugative transfer inhibitor, providing novel strategies to prevent the spread of AMR.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107370"},"PeriodicalIF":4.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557794","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":"Efficacy of Fosfomycin-Containing Regimens in Treating Severe Infections Caused by KPC-Producing Klebsiella pneumoniae and Carbapenem-Resistant Acinetobacter baumannii in Critically Ill Patients","authors":"A. Oliva ,&nbsp;A. Curtolo ,&nbsp;A. Falletta ,&nbsp;F. Sacco ,&nbsp;F. Lancellotti ,&nbsp;M. Carnevalini ,&nbsp;G. Ceccarelli ,&nbsp;G. Roma ,&nbsp;M. Bufi ,&nbsp;G. Magni ,&nbsp;G.M. Raponi ,&nbsp;M. Venditti ,&nbsp;C.M. Mastroianni","doi":"10.1016/j.ijantimicag.2024.107365","DOIUrl":"10.1016/j.ijantimicag.2024.107365","url":null,"abstract":"<div><h3>Background</h3><div>Fosfomycin (FOS) is gaining increasing importance as part of combination therapy for the treatment of carbapenem-resistant <em>Acinetobacter baumannii</em> (CRAB) and KPC-producing <em>Klebsiella pneumoniae</em> (KPC-Kp), thanks to its in vitro synergism with several antibiotics, high tissue distribution and good tolerability. We analyzed the effect on 30-day survival of FOS-containing regimens compared to non–FOS-containing regimens in critically ill patients admitted to the intensive care unit with CRAB or KPC-Kp infections. Secondary objectives were to evaluate clinical cure and microbiologic eradication in the FOS vs. the NO-FOS group.</div></div><div><h3>Methods</h3><div>This was a monocentric retrospective observational study including SARS-Cov2–negative critically ill patients with KPC-Kp or CRAB infection treated with combination antibiotic therapy with or without FOS for ≥48 h (FOS vs. NO-FOS groups, respectively). The primary outcome was 30-day mortality; secondary outcomes were clinical cure and microbiological eradication.</div></div><div><h3>Results</h3><div>Of the 78 patients analyzed, 26 (33.3%) were men, with a median (IQR) age and Charlson Comorbidity Index (CCI) of 67 years (53–74) and 4 (2–5), respectively. Septic shock was present in 18 patients (23.1%); 37 (47.4%) were receiving FOS, 41 (52.6%) were not receiving FOS; CRAB and KPC-Kp were isolated in 44 (56.4%) and 34 (43.6%) of patients, respectivley. Compared to NO-FOS, patients receiving FOS had a higher clinical cure (89.2% vs. 65.9%, <em>P</em> = 0.017), early (&lt;72 h) improvement (78.4% vs. 52.2%, <em>P</em> = 0.018), microbiological eradication (87.5% vs 62.2%, <em>P</em> = 0.027), and lower 7-, 14- and 30-day mortality (0% vs. 4.6%, <em>P</em> =0.027; 2.7% vs 22%, <em>P</em> = 0.016; and 13.5% vs. 34.2%, <em>P</em> = 0.039, respectively). This effect was particularly evident for infections sustained by KPC-Kp. On multivariable analysis, receiving FOS was independently associated with survival (hazard ratio = 0.29, 95% CI = 0.09-0.93, <em>P</em> = 0.038), confirmed after IPTW (HR = 0.501 95% CI = 0.25-0.98 <em>P</em> = 0.042).</div></div><div><h3>Conclusions</h3><div>FOS-containing regimens exhibited a higher clinical cure, higher microbiological eradication and reduced mortality compared with regimens not containing FOS in critically ill patients with CRAB and KPC-Kp infections.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107365"},"PeriodicalIF":4.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567711","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":"Orthoflavivirus zikaense (Zika) vaccines: What are we waiting for?","authors":"Alberto Cagigi ,&nbsp;Rosaria Tinnirello ,&nbsp;Gioacchin Iannolo ,&nbsp;Bruno Douradinha","doi":"10.1016/j.ijantimicag.2024.107367","DOIUrl":"10.1016/j.ijantimicag.2024.107367","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107367"},"PeriodicalIF":4.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567895","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":"Plasmid-mediated tigecycline resistance gene cluster tmexCD1-toprJ1 emerged in Klebsiella pneumoniae from weever (Lateolabrax maculatus)","authors":"Xun Gao ,&nbsp;Chao Yue ,&nbsp;Yingbo Gao ,&nbsp;Litao Lu ,&nbsp;Jian-Hua Liu ,&nbsp;Luchao Lv","doi":"10.1016/j.ijantimicag.2024.107368","DOIUrl":"10.1016/j.ijantimicag.2024.107368","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107368"},"PeriodicalIF":4.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568008","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.2024.107360","DOIUrl":"10.1016/j.ijantimicag.2024.107360","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107360"},"PeriodicalIF":4.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526905","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":"Assessment of lefamulin 20 µg disk versus broth microdilution when tested against common respiratory pathogens","authors":"Ying Cao ,&nbsp;Jichao Zhu ,&nbsp;Bingshao Liang ,&nbsp;Yan Guo ,&nbsp;Li Ding ,&nbsp;Fupin Hu","doi":"10.1016/j.ijantimicag.2024.107366","DOIUrl":"10.1016/j.ijantimicag.2024.107366","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the performance of the disk diffusion test with lefamulin 20 µg compared with the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution (BMD) method.</div></div><div><h3>Methods</h3><div>A total of 572 clinical stains, including 240 <em>Staphylococcus aureus</em>, 211 <em>Streptococcus pneumoniae</em>, and 121 <em>Haemophilus influenzae</em>, isolated from 71 medical centres from the China Antimicrobial Surveillance Network in 2020. BMD method and disk diffusion methods were performed according to CLSI. Categorical agreement (CA), major error (ME), and very ME (VME) were calculated.</div></div><div><h3>Results</h3><div>Lefamulin showed potent activity against <em>S. aureus, S. pneumoniae,</em> and <em>H. influenzae</em>. Using the BMD method, lefamulin inhibited 97.1% of <em>S. aureus</em> isolates at 0.25 mg/L; seven isolates were not susceptible. For <em>S. pneumoniae</em> and <em>H. influenzae,</em> the percentage of susceptibility to lefamulin was 100% and no non-susceptible strains were found in this study. Compared with the reference BMD method, the CA of the lefamulin 20 µg disk testing was 99.8% (571/572), with 14.3% (1/7) VME and no ME. In our study, VME was determined in <em>S. aureus</em>. For <em>S. pneumoniae</em> and <em>H. influenzae</em>, the VME was not determined due to the lack of lefamulin non-susceptible strains.</div></div><div><h3>Conclusions</h3><div>The lefamulin 20 µg disk diffusion testing showed excellent CA and ME with the reference BMD method for <em>S. aureus, S. pneumoniae,</em> and <em>H. influenzae</em>. The VME exceeding CLSI recommendations may be a bias due to fewer lefamulin non-susceptible isolates. Our results suggest that lefamulin non-susceptible isolates detected by disk diffusion should be confirmed by the reference BMD.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107366"},"PeriodicalIF":4.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499867","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":"Geographic differences in susceptibility profiles of potential non-class B carbapenemase-producing Enterobacterales isolates against ceftazidime-avibactam, meropenem-vaborbactam, colistin, amikacin, gentamicin, and tigecycline: Data from the Antimicrobial Testing Leadership and Surveillance, 2018–2022","authors":"Shio-Shin Jean ,&nbsp;Wen-Chien Ko ,&nbsp;I-Min Liu ,&nbsp;Po-Chuen Hsieh ,&nbsp;Po-Ren Hsueh","doi":"10.1016/j.ijantimicag.2024.107363","DOIUrl":"10.1016/j.ijantimicag.2024.107363","url":null,"abstract":"<div><div>To evaluate the susceptibility profiles of regional meropenem-resistant potential non-class B carbapenemase-producing Enterobacterales (CPE) isolates (without confirmation by phenotypic tests) against important antibiotics, we extracted data from the 2018-2022 Antimicrobial Testing Leadership and Surveillance. This data included susceptibility information of meropenem-resistant potential non-class B CPE isolates against indicated antibiotics – amikacin, gentamicin, ceftazidime-avibactam, colistin, meropenem-vaborbactam, and tigecycline – from sepsis patients hospitalized in intensive care units across six major regions. Carbapenemase-encoding genes of the tested CPE isolates, determined by multiplex PCR and Sanger sequencing, were also analyzed. Susceptibility breakpoints recommended by Clinical and Laboratory Standards Institute 2024 and US FDA criteria (for tigecycline only) against Enterobacterales were employed. A total of 1500 potential non-class B CPE isolates (89% of which were <em>Klebsiella pneumoniae</em>) were tested globally. Resistance rates to amikacin and gentamicin against the evaluated isolates were statistically higher in Africa/the Middle East, Europe, and India compared to other regions. A similar pattern was observed in the susceptibility of these potential CPE isolates to ceftazidime-avibactam and meropenem-vaborbactam. High colistin resistance rates were noted in Asia, Latin America, and Europe (29%–35%). Furthermore, the proportions of potential CPE isolates carrying genes encoding <em>bla</em>_OXA variants were notably higher among the tested CPE isolates in India, Europe, and Africa/the Middle East regions (99.2%, 53.3%, and 96.7%, respectively) compared to other regions. Trends in resistance to important antibiotics among potential non-class B CPE isolates warrant close monitoring.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107363"},"PeriodicalIF":4.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499868","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":"A contribution on the fosfomycin mechanism of resistance in multidrug-resistant organisms","authors":"Stefano Stracquadanio,&nbsp;Stefania Stefani","doi":"10.1016/j.ijantimicag.2024.107364","DOIUrl":"10.1016/j.ijantimicag.2024.107364","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107364"},"PeriodicalIF":4.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499866","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":"LuxS/AI-2 system facilitates the dissemination of antibiotic-resistant plasmids in Klebsiella pneumoniae","authors":"Ying Zhou ,&nbsp;Yang Yang ,&nbsp;Chunyang Wu ,&nbsp;Peiyao Zhou ,&nbsp;Haojin Gao ,&nbsp;Bingjie Wang ,&nbsp;Huilin Zhao ,&nbsp;Yanlei Xu ,&nbsp;Fangyou Yu","doi":"10.1016/j.ijantimicag.2024.107361","DOIUrl":"10.1016/j.ijantimicag.2024.107361","url":null,"abstract":"<div><div>Plasmid conjugation is a central mechanism driving the dissemination of antibiotic resistance in <em>Klebsiella pneumoniae</em>. However, the conjugative operon requires specific stimuli for activation. Identifying signals and elucidating the underlying mechanisms is crucial in combating plasmid spread. This study uncovers a key mechanism promoting the dissemination of high-risk plasmids, including IncFII, IncX3, and IncX4 types, in <em>K. pneumoniae</em>. In this study, increased donor density significantly enhanced conjugation, and transcript levels of both conjugation and AI-2 quorum sensing genes were markedly upregulated. Mutating the <em>luxS</em> and <em>lsrR</em> genes in <em>K. pneumoniae</em> 1678 decreased plasmid conjugation efficiency in the <em>1678ΔluxS</em> mutant, and significantly increased plasmid conjugation efficiency in the <em>1678ΔlsrR</em> mutant. RT-qPCR and β-galactosidase assays showed that LsrR represses transcription of relaxosome and T4CP genes, whereas AI-2 (synthesised by LuxS) activates their expression. AlphaFold 3 docking models indicate that LsrR may bind directly to IncX plasmid relaxase promoters, inhibiting their expression. Adding external AI-2 signals revealed no effect on plasmid conjugation when LsrR was absent, confirming the dependence of AI-2 signals on LsrR repression. In conclusion, AI-2-mediated signalling enhances donor density effects on plasmid conjugation by de-repressing LsrR-mediated suppression.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107361"},"PeriodicalIF":4.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499782","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}