Journal of Antimicrobial Chemotherapy最新文献

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Addition of probenecid to beta-lactam antibiotics in the treatment of skin and soft tissue infections: a systematic review. 在-内酰胺类抗生素治疗皮肤和软组织感染中添加丙戊酸:一项系统综述。
IF 4.1 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2026-11-03 DOI: 10.1093/jac/dkag376
Claudette Hewitt, Martin John Llewelyn, Elizabeth Cross
{"title":"Addition of probenecid to beta-lactam antibiotics in the treatment of skin and soft tissue infections: a systematic review.","authors":"Claudette Hewitt, Martin John Llewelyn, Elizabeth Cross","doi":"10.1093/jac/dkag376","DOIUrl":"10.1093/jac/dkag376","url":null,"abstract":"<p><strong>Background and objectives: </strong>Among patients presenting to hospital with skin and soft tissue infection (SSTI), up to 50% have already failed oral antibiotic treatment and 90% receive intravenous (IV) antibiotics.Probenecid prolongs serum concentrations of beta-lactam antibiotics. Probenecid-boosted oral treatment may be an alternative to IV. Alternatively, probenecid could allow less frequent dosing of narrow-spectrum IV agents (e.g. cefazolin), reducing dependence on ceftriaxone in ambulatory settings. This systematic review evaluated the effectiveness and safety of probenecid combined with beta-lactam antibiotics for SSTI treatment.</p><p><strong>Methods: </strong>MEDLINE and EMBASE were searched through February 2026. Eligible studies assessed the addition of probenecid to beta-lactam therapy in human participants with SSTIs and reported clinical outcomes or adverse effects.</p><p><strong>Results: </strong>Nine studies (over 1600 participants) were included, most evaluating once-daily IV cefazolin plus probenecid versus ceftriaxone or more frequent cefazolin dosing. Treatment success, failure, relapse and hospital admission rates were similar between groups, indicating that probenecid-boosted cefazolin performs comparably to standard regimens while offering a narrower-spectrum alternative to ceftriaxone. Evidence for oral beta-lactams plus probenecid was more limited but did not suggest inferiority. Adverse events, inconsistently reported, were generally mild and predominantly gastrointestinal, with possibly higher rates in the probenecid-containing regimens.</p><p><strong>Conclusions: </strong>Current evidence suggests probenecid may enable once-daily IV cefazolin as an alternative to ceftriaxone for SSTI, supporting narrower-spectrum antibiotics in ambulatory care. Evidence for using oral beta-lactams plus probenecid remains limited. A robust RCT is needed to determine clinical non-inferiority and acceptability of adverse effects. If effective, this approach could reduce IV complications, healthcare attendance and costs.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 12","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13732567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149321463","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}
引用次数: 0
Antimicrobial-resistant Pseudomonas aeruginosa in the USA: implications of a national surveillance gap. 美国耐抗生素铜绿假单胞菌:国家监测缺口的含义。
IF 4.1 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2026-11-03 DOI: 10.1093/jac/dkag382
Richard R Watkins, Tracy L Lemonovich, Robert A Bonomo
{"title":"Antimicrobial-resistant Pseudomonas aeruginosa in the USA: implications of a national surveillance gap.","authors":"Richard R Watkins, Tracy L Lemonovich, Robert A Bonomo","doi":"10.1093/jac/dkag382","DOIUrl":"https://doi.org/10.1093/jac/dkag382","url":null,"abstract":"<p><strong>Background: </strong>Surveillance data for Pseudomonas aeruginosa in the USA are distributed across systems designed for different purposes, potentially limiting standardized national surveillance of high-priority resistant phenotypes. We evaluated whether the Centers for Disease Control and Prevention (CDC) National Notifiable Diseases Surveillance System (NNDSS) can support surveillance of multidrug-resistant (MDR) P. aeruginosa and synthesized available CDC surveillance data to characterize the residual surveillance gap.</p><p><strong>Methods: </strong>We reviewed the 2026 NNDSS list of nationally notifiable conditions for P. aeruginosa. Because neither P. aeruginosa infection nor a resistant phenotype was present, NNDSS case counts were unable to be analysed. We therefore conducted a descriptive secondary analysis of CDC National Healthcare Safety Network (NHSN) reports for 2018-21 and the 2022 NHSN Antimicrobial Resistance (AR) Option report.</p><p><strong>Results: </strong>In 2018-21 adult NHSN data, 11.9% of tested P. aeruginosa isolates from device-associated infections were MDR, compared with 3.9% from surgical-site infections. Among central-line-associated bloodstream infection isolates, MDR proportions were highest in long-term acute-care hospitals (LTACHs, 25.3%), followed by hospital intensive-care units (14.2%), hospital wards (11.9%) and oncology units (8.5%). Among catheter-associated urinary tract infection isolates, MDR phenotype was observed in 20.8% of LTACH isolates. In the 2022 AR Option report, carbapenem non-susceptibility exceeded 10% among community-onset isolates and approached 20% among hospital-onset isolates.</p><p><strong>Conclusions: </strong>NNDSS cannot currently quantify the burden of MDR P. aeruginosa, but substantial resistance surveillance is available through NHSN and the CDC AR Laboratory Network. The principal gap is not an absence of surveillance data but fragmentation across systems with different populations, denominators, objectives and reporting mechanisms.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 12","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149334011","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}
引用次数: 0
Comment on: 'External validationof a model informed precision dosing software for cefotaxime for treating critical ill infants and children'. 评论:“用于治疗危重婴儿和儿童的头孢噻肟模型精确给药软件的外部验证”。
IF 4.1 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2026-11-03 DOI: 10.1093/jac/dkag381
Ercan Yılmaz, Nezihe Koker Özer, Erdem Topal
{"title":"Comment on: 'External validationof a model informed precision dosing software for cefotaxime for treating critical ill infants and children'.","authors":"Ercan Yılmaz, Nezihe Koker Özer, Erdem Topal","doi":"10.1093/jac/dkag381","DOIUrl":"https://doi.org/10.1093/jac/dkag381","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 12","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149321464","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}
引用次数: 0
Understanding integrase inhibitor resistance in Angola: a comparative analysis of INSTI-naive and INSTI-experienced individuals. 了解整合酶抑制剂在安哥拉的耐药性:对未感染和有感染经验的个体的比较分析。
IF 4.1 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2026-11-03 DOI: 10.1093/jac/dkag355
Bárbara Pocongo, Maria Furtado, Cláudia Bernardi, Lucrécia Jacinto, Aulória José, Jaime Urica, Rosa Torres, Francisco Vunge, Beatriz Almeida, Michael R Jordan, Carlos Jesus, Monick Lindenmeyer Guimarães, Cíntia Mayumi Ahagon, Giselle Lopes, Luís Brígido, Seth Inzaule, Ana B Abecasis, Ricardo Parreira, João Piedade, Victor Pimentel
{"title":"Understanding integrase inhibitor resistance in Angola: a comparative analysis of INSTI-naive and INSTI-experienced individuals.","authors":"Bárbara Pocongo, Maria Furtado, Cláudia Bernardi, Lucrécia Jacinto, Aulória José, Jaime Urica, Rosa Torres, Francisco Vunge, Beatriz Almeida, Michael R Jordan, Carlos Jesus, Monick Lindenmeyer Guimarães, Cíntia Mayumi Ahagon, Giselle Lopes, Luís Brígido, Seth Inzaule, Ana B Abecasis, Ricardo Parreira, João Piedade, Victor Pimentel","doi":"10.1093/jac/dkag355","DOIUrl":"10.1093/jac/dkag355","url":null,"abstract":"<p><strong>Background: </strong>Africa remains a major epicentre of the global HIV epidemic, with Central Africa exhibiting extensive HIV-1 genetic diversity that may influence the emergence and transmission of drug resistance mutations. Following World Health Organization recommendations, Angola initiated the national transition to dolutegravir (DTG)-based antiretroviral therapy (ART) in 2021. This study evaluated the frequency, patterns and temporal trends of HIV-1 drug resistance mutations before and after DTG implementation (2019-23), while also characterizing HIV-1 genetic diversity across Angolan provinces outside Luanda.</p><p><strong>Methods: </strong>A retrospective observational analytical study comparing pre- and post-Integrase strand transfer inhibitor (INSTI) introduction periods was conducted using plasma samples and dried blood spot cards from 17 provinces of Angola.</p><p><strong>Results: </strong>Of the 201 samples analysed, 102 were successfully sequenced for at least one coding region [protease (n = 65); reverse transcriptase (n = 66); integrase (IN) (n = 86)], comprising 48 INSTI-naive people living with HIV and 54 INSTI-experienced people living with HIV samples. Subtype C was the most prevalent (21.6%), followed by unique recombinant forms (20.6%), A1 (15.7%), F1 (13.7%), CRF02_AG (10.8%), G (8.8%) and other subtypes or recombinants (8.8%). Resistance to non-nucleoside reverse transcriptase inhibitors was the most common (68.2%; 95% CI 56.2-78.2), followed by nucleoside reverse transcriptase inhibitors (48.5%; 95% CI 36.8-60.3). Resistance to protease inhibitors (PIs) and INSTIs was lower, observed in 1.5% (95% CI 0.3-8.2) and 3.5% (95% CI 1.2-9.8), respectively.</p><p><strong>Conclusions: </strong>In this analysis, substantial HIV-1 genetic and epidemiological complexity was observed. In the context of the rapid scale-up of DTG-based ART, continued surveillance of INSTI resistance mutations has become increasingly important to inform evidence-based public health strategies aimed at preventing the transmission of drug-resistant HIV strains and optimizing ART regimens at the population level.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 12","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13729367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149321465","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}
引用次数: 0
No clinically relevant QTc prolongation with ceftibuten or ledaborbactam etzadroxil: concentration-QTc analyses from two phase I studies. 头孢布酮或利来博巴坦依扎罗西没有临床相关的QTc延长:来自两个I期研究的浓度-QTc分析。
IF 4.1 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2026-10-06 DOI: 10.1093/jac/dkag365
Borje Darpo, Hongqi Xue, Kamal A Hamed, Karine Litherland, Marc Engelhardt, Kathryn Lowe, Paul C McGovern
{"title":"No clinically relevant QTc prolongation with ceftibuten or ledaborbactam etzadroxil: concentration-QTc analyses from two phase I studies.","authors":"Borje Darpo, Hongqi Xue, Kamal A Hamed, Karine Litherland, Marc Engelhardt, Kathryn Lowe, Paul C McGovern","doi":"10.1093/jac/dkag365","DOIUrl":"10.1093/jac/dkag365","url":null,"abstract":"<p><strong>Objective: </strong>Ceftibuten and ledaborbactam etzadroxil are being developed as an oral fixed-dose combination for the treatment of complicated urinary tract infections caused by multidrug-resistant Enterobacterales. This study evaluated their effects on cardiac repolarization using concentration-QTc analyses.</p><p><strong>Methods: </strong>ECG and pharmacokinetic data from two randomized, single-centre, double-blind, placebo-controlled, phase I, dose-escalation studies in healthy adults (ClinicalTrials.gov: NCT04314206 and NCT04243863) were analysed using concentration-QTc modelling. Thirty-six participants were randomized to the ceftibuten study (27 active, nine placebo) and 48 to the ledaborbactam etzadroxil study (36 active, 12 placebo). Linear mixed-effects models characterized the relationship between plasma concentrations and placebo-corrected change from baseline in Fridericia-corrected QT interval (ΔΔQTcF). Model-based predictions estimated QTc effects across observed and clinically relevant plasma concentrations.</p><p><strong>Results: </strong>Neither agent produced clinically relevant changes in ECG parameters. Concentration-QTc analyses demonstrated no statistically or clinically meaningful relationship between plasma concentrations and ΔΔQTcF. An effect on ΔΔQTcF exceeding the regulatory threshold of 10 ms could be excluded at plasma concentrations up to 44 µg/mL for cis-ceftibuten (the predominant and more potent isomer), 2.2 µg/mL for trans-ceftibuten, 30.3 µg/mL for ledaborbactam (active drug), and 2.6 µg/mL for ledaborbactam etzadroxil (prodrug). A small, transient, not clinically relevant increase in heart rate was observed with ceftibuten, whereas ledaborbactam etzadroxil had no clinically meaningful effect on heart rate.</p><p><strong>Conclusions: </strong>Ceftibuten and ledaborbactam etzadroxil demonstrated no clinically relevant effects on cardiac repolarization or ECG parameters. Concentration-QTc analyses excluded clinically meaningful QTc effects at and above anticipated therapeutic plasma concentrations, supporting the cardiac safety profile of this oral fixed-dose combination.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 11","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13691604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244855","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}
引用次数: 0
Updated UK good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT): ensuring quality of care and antimicrobial stewardship in an evolving healthcare landscape. 更新的英国门诊肠外抗菌治疗(OPAT)良好实践建议:在不断发展的医疗保健环境中确保护理质量和抗菌管理。
IF 4.1 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2026-10-06 DOI: 10.1093/jac/dkag327
Ann L Noble, Sanjay Patel, Mark Gilchrist, R Andrew Seaton
{"title":"Updated UK good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT): ensuring quality of care and antimicrobial stewardship in an evolving healthcare landscape.","authors":"Ann L Noble, Sanjay Patel, Mark Gilchrist, R Andrew Seaton","doi":"10.1093/jac/dkag327","DOIUrl":"https://doi.org/10.1093/jac/dkag327","url":null,"abstract":"<p><p>Outpatient parenteral antimicrobial therapy (OPAT) offers safe, effective and patient-centred care for patients with infections requiring IV or complex oral antimicrobial therapy. The UK OPAT Good Practice Recommendations (GPRs) have recently been updated through a systematic literature review, expert consensus and consultation. In this article we outline the key changes in the updated GPRs. There are five new recommendations on (i) self-administration, (ii) OPAT in hard-to-reach groups, (iii) patient education, (iv) developing monitoring protocols for patients on complex oral antimicrobials and on new parenteral administration routes and regimes, and (v) equitable provision of care; and two amended recommendations, on (i) thromboprophylaxis, and (ii) early collaboration with vascular access teams. Overall, the literature demonstrates the increasing confidence of OPAT services in managing complex and comorbid patients, and shows evidence of innovation and collaboration. OPAT has the potential to improve clinical care and antimicrobial stewardship in patients with complex infections in an evolving healthcare landscape.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 11","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244815","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}
引用次数: 0
Determinants of levofloxacin prophylaxis failure in high-risk haematology patients: a prospective study integrating resistant colonization and pharmacokinetic/pharmacodynamic target attainment-authors' response. 高危血液病患者左氧氟沙星预防失败的决定因素:一项整合耐药定植和药代动力学/药效学目标实现的前瞻性研究——作者的反应
IF 4.1 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2026-10-06 DOI: 10.1093/jac/dkag342
Cemre Boşnak, Gökhan Metan, Pınar Zarakolu, Elifcan Aladağ Karakulak, Aslı Pınar, Hakan Göker, Jason A Roberts, Maria Patricia Hernandez-Mitre, Murat Akova
{"title":"Determinants of levofloxacin prophylaxis failure in high-risk haematology patients: a prospective study integrating resistant colonization and pharmacokinetic/pharmacodynamic target attainment-authors' response.","authors":"Cemre Boşnak, Gökhan Metan, Pınar Zarakolu, Elifcan Aladağ Karakulak, Aslı Pınar, Hakan Göker, Jason A Roberts, Maria Patricia Hernandez-Mitre, Murat Akova","doi":"10.1093/jac/dkag342","DOIUrl":"https://doi.org/10.1093/jac/dkag342","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 11","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164816","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}
引用次数: 0
MPT64 secretion as a viability-associated immunoassay readout for rapid phenotypic drug susceptibility classification of Mycobacterium tuberculosis: a proof-of-concept study. MPT64分泌作为结核分枝杆菌快速表型药物敏感性分类的活力相关免疫分析读数:一项概念验证研究
IF 4.1 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2026-10-06 DOI: 10.1093/jac/dkag358
Yoshiro Murase, Rikiya Takeuchi, Yoshiharu Ohtaki, Makiko Hosoya, Akio Aono, Kinuyo Chikamatsu, Yuta Morishige, Yuriko Igarashi, Joseph Edwin L Bascuña, Gel Anne Marie V Atienza, Angeline Grace A Sedusta, Catherine Ann P L Sacopon, Ramón P Basilio, Midori Kato-Maeda, Satoshi Mitarai
{"title":"MPT64 secretion as a viability-associated immunoassay readout for rapid phenotypic drug susceptibility classification of Mycobacterium tuberculosis: a proof-of-concept study.","authors":"Yoshiro Murase, Rikiya Takeuchi, Yoshiharu Ohtaki, Makiko Hosoya, Akio Aono, Kinuyo Chikamatsu, Yuta Morishige, Yuriko Igarashi, Joseph Edwin L Bascuña, Gel Anne Marie V Atienza, Angeline Grace A Sedusta, Catherine Ann P L Sacopon, Ramón P Basilio, Midori Kato-Maeda, Satoshi Mitarai","doi":"10.1093/jac/dkag358","DOIUrl":"10.1093/jac/dkag358","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate MPT64 secretion as a viability-associated readout for rapid phenotypic drug susceptibility testing (pDST) of Mycobacterium tuberculosis.</p><p><strong>Methods: </strong>We evaluated MPT64-pDST in 130 M. tuberculosis strains: clinical isolates, WHO quality assessment strains and in vitro-selected resistant mutants (for linezolid only). We assessed the diagnostic performance of MPT64-pDST for determining susceptibility to rifampicin, isoniazid and moxifloxacin. As a secondary objective, we explored its performance for linezolid and bedaquiline. MPT64 was quantified by chemiluminescent enzyme immunoassay, and susceptibility was inferred from Log2 fold change relative to drug-free controls. Reference standards were minimum inhibitory concentration testing for rifampicin, isoniazid, linezolid and bedaquiline and MGIT-based DST for moxifloxacin. Performance was evaluated using receiver operating characteristic analysis, full-dataset Youden-optimal candidate cutoffs and 2000-iteration stratified bootstrap out-of-bag (OOB) internal validation.</p><p><strong>Results: </strong>Using drug-specific full-dataset Youden-optimal candidate cutoffs, MPT64-pDST showed high categorical agreement with reference DST, with no false-resistant classifications for rifampicin, isoniazid or moxifloxacin. Resistance-detection sensitivity was 100% for rifampicin, 98% for isoniazid and 90% for moxifloxacin, and out-of-bag bootstrap estimates were comparable to the full-dataset estimates. Exploratory analyses for linezolid demonstrated separation between susceptible and resistant mutants. The single bedaquiline-resistant isolate was clearly distinguishable from 39 bedaquiline-susceptible isolates.</p><p><strong>Conclusions: </strong>These findings provide proof of concept that the immunoassay-based MPT64-pDST can enable rapid phenotypic susceptibility classification for rifampicin, isoniazid and moxifloxacin. Further validation in larger isolate collections, including isolates with borderline phenotypes, is warranted.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 11","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13714544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149286973","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}
引用次数: 0
In vitro activity of cefiderocol against Burkholderia cepacia complex and Burkholderia gladioli clinical isolates from cystic fibrosis patients in the United States. 头孢地罗对美国囊性纤维化患者中产洋葱伯克霍尔德菌复合物和剑兰伯克霍尔德菌临床分离株的体外活性研究
IF 4.1 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2026-10-06 DOI: 10.1093/jac/dkag347
Maria F Mojica, Elise T Zeiser, Scott A Becka, Lindsay J Caverly, John J Lipuma, Robert A Bonomo, Krisztina M Papp-Wallace
{"title":"In vitro activity of cefiderocol against Burkholderia cepacia complex and Burkholderia gladioli clinical isolates from cystic fibrosis patients in the United States.","authors":"Maria F Mojica, Elise T Zeiser, Scott A Becka, Lindsay J Caverly, John J Lipuma, Robert A Bonomo, Krisztina M Papp-Wallace","doi":"10.1093/jac/dkag347","DOIUrl":"10.1093/jac/dkag347","url":null,"abstract":"<p><strong>Background: </strong>Burkholderia cepacia complex (Bcc) and Burkholderia gladioli are intrinsically multidrug-resistant pathogens that cause chronic pulmonary infections in individuals with cystic fibrosis (CF) and severe infections in other vulnerable populations. Therapeutic options remain limited as resistance to commonly used agents continues to emerge.</p><p><strong>Objectives: </strong>To evaluate the in vitro activity of cefiderocol against a collection of Bcc and B. gladioli isolates from individuals with CF in the USA and to compare these findings with historical susceptibility data for 16 other antimicrobial agents.</p><p><strong>Methods: </strong>A total of 150 clinical isolates representing multiple Bcc species and B. gladioli were tested. Cefiderocol MICs were determined using iron-depleted broth microdilution (ID-BMD) and iron-depleted agar dilution (ID-AD). Species-specific MIC distributions were assessed, and cefiderocol activity was compared with historical MIC data for 16 other antimicrobial agents previously tested against the same isolate panel. Mechanistic studies evaluated blaPenA expression and hydrolysis of cefiderocol by purified PenA1.</p><p><strong>Results: </strong>Cefiderocol MIC50 and MIC90 values were 0.06 and 8 mg/L, and 0.03 and 8 mg/L, respectively, by both ID-BMD and ID-AD. Low MIC90 values were observed for Burkholderia cenocepacia, B. cepacia, B. gladioli, and most 'other Bcc' species, whereas elevated MIC90 values were detected for Burkholderia multivorans and Burkholderia vietnamiensis. Cefiderocol demonstrated the lowest MIC50 values when compared with historical data for 16 other agents; did not induce blaPen expression; and was not hydrolysed by purified PenA1.</p><p><strong>Conclusions: </strong>Cefiderocol demonstrated broad in vitro activity against Bcc and B. gladioli isolates from individuals with CF and showed stability against key β-lactamase-mediated resistance mechanisms.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 11","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13712140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149286991","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}
引用次数: 0
Genomic evidence of clonal and IncX3 plasmid-mediated dissemination of blaNDM-7 in the Klebsiella pneumoniae complex. 克隆和IncX3质粒介导的blaNDM-7在肺炎克雷伯菌复合体中的传播的基因组证据。
IF 4.1 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2026-10-06 DOI: 10.1093/jac/dkag346
Yujing Zhang, Guqi Ren, Jing Wu, Jun Xu, Yan Ji, Guiling Li, Zhenyu Wang, Jing Wang, Xinan Jiao, Lin Sun
{"title":"Genomic evidence of clonal and IncX3 plasmid-mediated dissemination of blaNDM-7 in the Klebsiella pneumoniae complex.","authors":"Yujing Zhang, Guqi Ren, Jing Wu, Jun Xu, Yan Ji, Guiling Li, Zhenyu Wang, Jing Wang, Xinan Jiao, Lin Sun","doi":"10.1093/jac/dkag346","DOIUrl":"https://doi.org/10.1093/jac/dkag346","url":null,"abstract":"<p><strong>Background: </strong>Carbapenem-resistant Enterobacterales (CRE), particularly those carrying New Delhi metallo-β-lactamase (NDM) variants, pose a major global health threat. Among these, NDM-7 has attracted increasing attention due to its enhanced carbapenemase activity and clinical relevance. This study investigated the prevalence, genomic characteristics and dissemination of blaNDM-7-positive Klebsiella pneumoniae complex isolates from clinical and environmental sources in Yangzhou, China.</p><p><strong>Methods: </strong>A total of 401 clinical isolates, 282 hospital surface swabs and 366 wastewater samples collected between 2018 and 2024 were screened for blaNDM. Antimicrobial susceptibility testing and whole-genome sequencing were performed to characterize resistance profiles, genomic features and phylogenetic relationships. Conjugation and serial-passage assays were used to assess plasmid transferability and stability, respectively.</p><p><strong>Results: </strong>Seven blaNDM-7-positive isolates were identified, including one clinical isolate, one hospital environmental isolate and five wastewater isolates. All exhibited multidrug resistance. The blaNDM-7 gene was located on highly conserved ∼46 kb IncX3 plasmids that exhibited high conjugation frequencies (10-5-10-4) and stability (96.0%-98.7% mean retention after approximately 600 generations). Phylogenetic analysis revealed close genomic relatedness among the six ST196 K. quasipneumoniae isolates recovered from different sources, with only 0-7 core-genome SNP differences. All six isolates were recovered within approximately 6 months, consistent with recent common ancestry and possible clonal dissemination across settings.</p><p><strong>Conclusions: </strong>The close genomic relatedness of ST196 isolates from different sources supports possible clonal dissemination, while the high conservation, transferability and stability of IncX3 plasmids highlight their important role in the dissemination of blaNDM-7. These findings underscore the importance of continued genomic surveillance of blaNDM-7 and its associated mobile genetic elements across clinical and environmental settings.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 11","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194009","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}
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