Journal of Antimicrobial Chemotherapy最新文献

{"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}

{"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}

{"title":"Phylogenetic diversification of the PoxtA ribosomal protection determinant.","authors":"Lara M Almeida, Felipe M Zorzi, Kawany M Araujo, Joas L Silva, Andrea M Moreno, Paulo Bispo, Michael S Gilmore","doi":"10.1093/jac/dkag339","DOIUrl":"https://doi.org/10.1093/jac/dkag339","url":null,"abstract":"<p><strong>Objectives: </strong>Three ATP-binding cassette subfamily F (ABC-F) PoxtA protein sequences are currently represented in NCBI's Pathogen Detection Reference Gene Catalog (WP_002415638.1, WP_209691075.1, and WP_094899500.1), while the number of publicly available sequences has steadily increased. We therefore conducted a curated survey of PoxtA homologue diversity, distribution, amino acid variability, and dissemination-associated genetic contexts.</p><p><strong>Methods: </strong>WP accessions were retrieved using BLASTp nr and a corresponding data package was obtained from NCBI Datasets v18.0.1. Proteins were aligned with MAFFT v7.525, clustered with CD-HIT v4.8.1, and maximum likelihood trees inferred in IQ-TREE v2.4.0. Gene occurrence derived from GCF assemblies containing host or source metadata. Genetic contexts were then investigated through sequence alignments of genomic regions extracted from these datasets.</p><p><strong>Results: </strong>Among 83 non-redundant PoxtA-related WP accessions retrieved, 21 homologues clustered with canonical RefSeq PoxtA proteins, while the remaining proteins were more distantly related to ABC-F. Predominantly associated with Bacillota, homologues exhibited broad distribution across clinical, agricultural, food-associated, and environmental sources. Substitutions potentially affecting their ribosome interactions were identified mainly within the Arm subdomain and the antibiotic-resistance domain. Genomes encoding homologues exhibited diverse genetic contexts, including partial conservation of Tn6657, intact Tn6246 and Tn8026 structures, and atypical contexts carrying additional resistance genes.</p><p><strong>Conclusions: </strong>Homologue diversification suggests ongoing adaptation and highlights an expanding repertoire of amino acid substitutions with yet unresolved structural and functional impacts. Genetic contexts likely underlie intra- and interspecies horizontal dissemination of homologue genes by promoting co-selection under antimicrobial selective pressures.</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":"149166569","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":"Beyond susceptibility: pharmacokinetic and pharmacodynamic constraints of existing oral antibiotics in extensively drug-resistant typhoid fever.","authors":"Yamuna Devi Bakthavatchalam, Priscilla Rupali, Jacob John, Kamini Walia, Vasant Nagvekar, Balaji Veeraraghavan","doi":"10.1093/jac/dkag332","DOIUrl":"https://doi.org/10.1093/jac/dkag332","url":null,"abstract":"<p><p>Salmonella Typhi is an invasive pathogen with sustained bacteraemia and intracellular persistence, requiring therapy that achieves systemic exposure and intracellular penetration. Clinical efficacy should remain central to therapeutic decision-making, while pharmacokinetic/pharmacodynamic (PK/PD) analyses provide complementary insights into dose optimization and the pharmacological limitations of candidate therapies. Oral therapy remains central to typhoid fever management, particularly in South and Southeast Asia, where most patients are managed in the outpatient setting. However, the emergence of MDR and extensively drug-resistant (XDR) S. Typhi has substantially narrowed the available oral treatment options. Azithromycin remains the only widely available oral agent with established clinical efficacy, but emerging resistance threatens its continued utility. Several alternative oral agents, including mecillinam, faropenem, tebipenem, fosfomycin and β-lactam/β-lactamase inhibitor combinations, demonstrate favourable in vitro activity against S. Typhi. However, robust clinical efficacy and contemporary PK/PD data are lacking to support their use against MDR and XDR S. Typhi. Addressing these evidence gaps through integrated PK/PD investigations and prospective clinical trials will be essential to expand the oral therapeutic armamentarium for typhoid fever.</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":"149127540","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":"Genomic determinants of penicillin G susceptibility and cefazolin inoculum effect in methicillin-susceptible Staphylococcus aureus bloodstream isolates.","authors":"Samantha Poloni, Adeline Gagnon, Benoit Valot, Alexandre Meunier, Didier Hocquet, Xavier Bertrand, Adrien Biguenet, Kevin Bouiller","doi":"10.1093/jac/dkag328","DOIUrl":"https://doi.org/10.1093/jac/dkag328","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to describe penicillin G susceptibility, blaZ diversity, and genetic determinants of the cefazolin inoculum effect (CfzIE) among MSSA bloodstream isolates.</p><p><strong>Methods: </strong>The first three non-duplicate MSSA isolates recovered each month from blood cultures at our French university hospital between January 2010 and December 2023 were selected. Whole-genome sequencing was performed using the Illumina NextSeq platform to characterize blaZ and its genetic context. Susceptibility to penicillin G and the CfzIE were assessed using phenotypic methods.</p><p><strong>Results: </strong>Among 488 MSSA isolates, 373 (76.5%) carried blaZ, of which 119 (31.9%) exhibited CfzIE. Thirty BlaZ allotypes were identified overall; 26 were included in the genetic determinant analysis after exclusion of isolates with multiple or truncated blaZ. In multivariable analysis, BlaZA3 was strongly associated with CfzIE (aOR, 15.72; 95% CI, 3.33-74.24; P < 0.001), as was CC7 (aOR, 5.48; 95% CI, 1.45-20.69; P = 0.011). Among BlaZA3 isolates, CfzIE was mainly observed with complete blaR1. Among 122 isolates with a penicillin G inhibition zone ≥26 mm, seven carried blaZ, including six with sharp zone edges and truncated blaZ sequences.</p><p><strong>Conclusion: </strong>CfzIE was mainly associated with a BlaZA3-related genetic background, particularly in the presence of complete blaR1, rather than with blaZ type alone. Approximately one-quarter of MSSA bloodstream isolates were susceptible to penicillin G, and rare phenotype-genotype discrepancies were associated with truncated blaZ sequences.</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":"149110015","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":"Direct measurement of eravacycline effluent concentrations during continuous venovenous haemodiafiltration: negligible clearance in a critically ill patient.","authors":"Guanghui Chen, Qiang Qu, Yanyan Zhou, Dongshan Zhang, Jian Qu","doi":"10.1093/jac/dkag345","DOIUrl":"https://doi.org/10.1093/jac/dkag345","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":"149172328","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":"Comment on: Determinants of levofloxacin prophylaxis failure in high-risk haematology patients: a prospective study integrating resistant colonization and pharmacokinetic/pharmacodynamic target attainment.","authors":"Basavaraj Poojar","doi":"10.1093/jac/dkag341","DOIUrl":"https://doi.org/10.1093/jac/dkag341","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":"149136347","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 and safety of switching to once-daily oral doravirine plus raltegravir in virologically suppressed people with HIV-1: a randomized, open-label, multicentre phase 2 study (DORAL).","authors":"Romain Palich, Minh P Lê, Antonella Castagna, Clotilde Allavena, Andrea Antinori, Diana Canetti, Juan Tiraboschi, Claudine Duvivier, Esteban Martinez, Pere Domingo, Salima Barkat, Yasmine Dudoit, Lydie Béniguel, Gilles Peytavin, Anne-Geneviève Marcelin, Cathia Soulié, Lambert Assoumou, Christine Katlama","doi":"10.1093/jac/dkag336","DOIUrl":"10.1093/jac/dkag336","url":null,"abstract":"<p><strong>Background: </strong>We evaluated the efficacy and safety of a once-daily oral two-drug regimen (2DR) combining doravirine and raltegravir in virologically suppressed people with HIV (PWH).</p><p><strong>Methods: </strong>DORAL is a multicentre, open-label, randomized phase II trial conducted in France, Italy, and Spain. Virologically suppressed adults receiving stable antiretroviral therapy (ART), naïve to doravirine and without raltegravir resistance, were randomized (2:1) either to switch immediately to doravirine (100 mg) plus raltegravir (1200 mg) or to continue baseline ART until week 48 before switching to doravirine plus raltegravir. The primary endpoint was virological failure (VF; confirmed plasma HIV-1-RNA ≥50 copies/mL) at week 48. Secondary endpoints included maintenance of virological suppression through W96, immunological outcomes, safety, and pharmacokinetics in a genital sub-study.</p><p><strong>Results: </strong>Among 114 participants (median age, 57 years; median CD4 count, 700 cells/mm3; median duration of virological suppression, 10 years), one VF occurred by week 48 in the immediate-switch group (1.3%; 95% CI, 0.0-6.9); none occurred in the delayed-switch group. No additional VF was observed through week 96. Immunological parameters remained stable during follow-up. Three adverse events considered related to doravirine and raltegravir led to treatment discontinuation. One grade 3 adverse event (anxiety), considered related to study treatment, was reported. In the genital sub-study, drug concentrations exceeded inhibitory thresholds in most samples, with infrequent detection of low-level seminal HIV-1-RNA.</p><p><strong>Conclusions: </strong>This proof-of-concept phase II switch trial supports the feasibility of a once-daily doravirine plus raltegravir 2DR in selected PWH, particularly when minimizing drug-drug interactions or avoiding NRTI exposure is a priority.</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":"149127599","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":"Sitagliptin attenuates urease-associated phenotypes and potentiates meropenem in multidrug-resistant Gram-negative clinical isolates: a preliminary repurposing study.","authors":"Afaf Eladl, Hisham A Abbas, Marwa Ibrahim Abd El-Hamid, Samar S Elbaramawi, Nada A Noureldin, Shaimaa I Nazeih","doi":"10.1093/jac/dkag344","DOIUrl":"https://doi.org/10.1093/jac/dkag344","url":null,"abstract":"<p><strong>Background: </strong>Urease contributes to urinary tract pathogenesis and catheter encrustation, whereas metallo-β-lactamases contribute to carbapenem resistance.</p><p><strong>Objectives: </strong>We investigated whether the dipeptidyl peptidase-4 inhibitor sitagliptin attenuates urease-associated phenotypes and potentiates meropenem against selected multidrug-resistant Gram-negative clinical isolates.</p><p><strong>Methods: </strong>Urease-associated activity was assessed in whole-cell suspensions and crude lysates of Proteus mirabilis. Alkalinization, crystal formation in artificial urine, and catheter-associated total biomass were also examined. Meropenem potentiation was evaluated by combined-disk and chequerboard assays, and meropenem-hydrolyzing activity was measured. Relative transcript abundance was assessed by quantitative reverse-transcription PCR, and docking was used to generate structural hypotheses. Vero-cell metabolic activity was evaluated by the MTT assay.</p><p><strong>Results: </strong>Sitagliptin (2000 µg/mL; one-eighth of its MIC) inhibited urease-associated assay signal by 53.2%-55.2% in whole-cell suspensions and crude lysates, reduced the urease-driven pH increase from 9.21 to 7.34 after 24 h, and reduced crystal-violet-stained catheter-associated biomass by 83.6%. It reduced the apparent meropenem hydrolysis signal in periplasmic extracts by 33%-55% and reduced meropenem MICs by 16- to 64-fold in combination assays, with FICI values of 0.1406-0.1875. In the Vero-cell assay, viability at 2000 µg/mL was 94.4%, and a 50% reduction in viability was not observed within the tested range. Sitagliptin exposure was associated with reduced relative transcript abundance of ureR, ureC, blaNDM, blaIMP, and blaVIM. Docking generated binding poses near catalytic metal centres.</p><p><strong>Conclusions: </strong>In the tested preparations and isolate panel, sitagliptin attenuated urease-associated phenotypes, reduced apparent meropenem-hydrolyzing activity and potentiated meropenem, supporting its further investigation as a potential anti-virulence and antibiotic-adjuvant candidate.</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":"149194073","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":"Intergeneric mobilization of a genomic island mediated by a helper integrative conjugative element from Streptococcus suis to Enterococcus faecalis.","authors":"Kaiwei Nie, Jiaqi Zhao, Cai Yin, Shushu Gu, Hui Ji, Xingyang Dai, Xiaoming Wang, Liping Wang, Jinhu Huang","doi":"10.1093/jac/dkag338","DOIUrl":"https://doi.org/10.1093/jac/dkag338","url":null,"abstract":"<p><strong>Background and objectives: </strong>Mobile genetic elements drive antimicrobial-resistance dissemination in Gram-positive pathogens. In Streptococcus suis we previously identified a genomic island, GISsuJHJ17_rpsI, integrated at the conserved rpsI locus and carrying erm(B) and aadE. Here we investigated the genetic features and helper functions associated with mobilization of this island, including its transfer from S. suis to E. faecalis.</p><p><strong>Methods: </strong>Genetic annotation established that GISsuJHJ17_rpsI lacks a self-encoded conjugation apparatus but harbours an origin of transfer (oriT) sharing ∼85% nucleotide identity with the co-resident integrative and conjugative element (ICE). We performed filter-mating assays to test ICE-mediated mobilization in trans, constructed precise deletions of oriTGISsuJHJ17 and of the ICE relaxase, carried out complementation, and assessed fitness by growth and head-to-head competition of transconjugants.</p><p><strong>Results: </strong>Filter-mating assays showed that mobilization of GISsuJHJ17_rpsI in the S. suis recipient model required the helper-ICE relaxase and the candidate GI oriT region. Deletion of either determinant yielded no verified transconjugants under the assay conditions, whereas relaxase complementation and chromosomal oriT repair restored detectable transfer. These findings support a model in which the helper ICE provides the DNA-processing function required for GI mobilization, using the co-resident ICE transfer apparatus, as inferred from the ICE gene content. Fitness assays revealed no measurable growth defect or competitive disadvantage associated with acquisition of GISsuJHJ17_rpsI, indicating a minimal short-term fitness cost.</p><p><strong>Conclusions: </strong>These findings show that GISsuJHJ17_rpsI can transfer from S. suis to E. faecalis and integrate at an rpsI-associated site. In the S. suis recipient model, mobilization required the helper-ICE relaxase and the GISsuJHJ17_rpsI oriT region, supporting a helper-ICE-dependent mechanism for genomic-island mobilization.</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":"149136410","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}