Journal of Antimicrobial Chemotherapy最新文献

{"title":"Ivermectin dosing for children under 2 years.","authors":"Wenyu Yang, Andrew Steer, Ben Coghlan, Khampheng Phongluxa, Xiao Zhu, Amanda Gwee","doi":"10.1093/jac/dkaf344","DOIUrl":"https://doi.org/10.1093/jac/dkaf344","url":null,"abstract":"<p><strong>Objectives: </strong>Ivermectin is effective against scabies but not licensed for children weighing <15 kg. We aimed to identify an ivermectin dosing strategy for children aged <2 years.</p><p><strong>Methods: </strong>Doses for three age subgroups under 2 years were simulated by incorporating a maturation function for metabolizing enzymes into a population pharmacokinetic (PopPK) model to achieve median plasma AUC0-∞ between 80% and 125% of that observed in children aged 5-15 years receiving the standard 200 μg/kg dose (AUC0-∞ 976 μg/L h). Patient covariates were sampled from the National Health and Nutrition Examination Survey dataset. Final doses were rounded to feasible fractions of a 3 mg tablet.</p><p><strong>Results: </strong>For infants aged 3-7 months, a 0.75 mg dose (one-fourth tablet) resulted in a median AUC0-∞ of 835 μg/L h [IQR: 632-1017]; for 8-12 months, a 1.5 mg dose (one-half tablet) yielded 848 μg/L h [IQR: 774-934]; and for 13-24 months, a 3 mg dose (one tablet) resulted in 1033 μg/L h [IQR: 943-1173]. All doses achieved median exposures within 80%-125% of the reference AUC in older children.</p><p><strong>Conclusions: </strong>A dosing strategy for ivermectin in children aged 3 months-2 years was developed using a CYP3A4 maturation-based PopPK model. This regimen will be evaluated in an upcoming clinical trial to inform safe and effective scabies treatment in young children.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124953","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":"Possible increased risk of Epstein-Barr virus (EBV) infection and post-transplant lymphoproliferative disease (PTLD) in letermovir-exposed haematopoietic cell transplantation recipients.","authors":"Jose F Camargo, Saanvi S Singireddy, Anthony D Anderson","doi":"10.1093/jac/dkaf348","DOIUrl":"https://doi.org/10.1093/jac/dkaf348","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124881","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 toxin-antitoxin system SavRS contributes to vancomycin resistance in vancomycin-intermediate Staphylococcus aureus by mediating cell wall thickening.","authors":"Weifeng Xu, Ping Yan, Yujie Li, Baolin Sun","doi":"10.1093/jac/dkaf325","DOIUrl":"https://doi.org/10.1093/jac/dkaf325","url":null,"abstract":"<p><strong>Background: </strong>The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) has significantly challenged the treatment of S. aureus infection. Toxin-antitoxin (TA) systems have been reported to mediate bacterial stress adaptation and virulence, but their role in vancomycin resistance remains elusive. This study investigated the vancomycin resistance mechanism regulated by the TA system SavRS in VISA.</p><p><strong>Methods: </strong>savRS mutants in Mu50 and XN108 were generated via homologous recombination. To investigate the regulatory mechanism of vancomycin resistance mediated by savRS in VISA, phenotypic analyses including MICs, growth kinetics and cell wall thickness measurements were performed. Expression of cell wall synthesis-related genes was analysed using quantitative RT-PCR (RT-qPCR) and promoter-lacZ reporter assay. Electrophoretic mobility shift assay (EMSA) was performed to assess the binding of SavRS to the promoters of the cell wall synthesis-related genes. Pull-down assay identified an upstream regulatory element of savRS associated with vancomycin resistance. Quantitative assessment of bacterial burden in murine organ systems following vancomycin administration revealed the critical regulatory role of savRS in mediating vancomycin resistance in vivo.</p><p><strong>Results: </strong>Compared with the WT, the savRS mutant exhibited enhanced vancomycin sensitivity, accelerated growth and reduced cell wall thickness. Correspondingly, RT-qPCR revealed marked down-regulation of the cell wall synthesis-related genes (glyS, dltA, scdA, pbp2, ddl). EMSA and promoter-lacZ reporter assay confirmed direct binding of SavRS to a conserved promoter motif, MGHYYTCCTCA. Pull-down assay identified UspA as an upstream regulator of SavRS, demonstrating that UspA directly controls savRS transcription and modulates VISA resistance. Mouse infection experiments showed that savRS promotes VISA to vancomycin resistance in vivo.</p><p><strong>Conclusions: </strong>SavRS critically regulates vancomycin resistance in VISA.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124960","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 first-line lamivudine/dolutegravir antiretroviral therapy in persons with HIV: real-life data from the ICONA Foundation cohort.","authors":"Alessandra Vergori, Alessandro Cozzi-Lepri, Sergio Lo Caputo, Alessandro Tavelli, Valentina Mazzotta, Elisabetta Schiaroli, Giancarlo Orofino, Cristina Mussini, Silvia Nozza, Antonella Cingolani, Andrea Antinori, Antonella d'Arminio Monforte","doi":"10.1093/jac/dkaf345","DOIUrl":"https://doi.org/10.1093/jac/dkaf345","url":null,"abstract":"<p><strong>Objectives: </strong>This analysis aimed to evaluate the rate of failure of first-line lamivudine/dolutegravir in a real-world setting and assess the effectiveness among people with HIV (PWH) at higher risk of suboptimal response.</p><p><strong>Methods: </strong>The study included PWH from the ICONA cohort who started first-line lamivudine/dolutegravir between 2016 and 2024. The primary endpoint was time to treatment failure (TF), defined as virological failure (VF, two consecutive HIV-RNA of >50 copies/mL >6 months after treatment initiation) or discontinuation due to toxicity/lack virological control/non-adherence or death for any cause. Secondary endpoints were time to treatment discontinuation for any reason (TD) and pure VF. Main exposures of interest were baseline CD4 and HIV-RNA, age, sex at birth and nation of birth. Standard survival analysis and Cox regression models were used.</p><p><strong>Results: </strong>Among 446 participants, after a median follow-up of 22 months, 4.3% (n = 19) experienced TF, the 3 year cumulative probability was 5.8% (95% CI: 2.9%-8.7%). Baseline CD4 count was associated with a 3-fold higher risk of TF, which decreased after adjustments. Higher viral loads (>100 000 copies/mL), age >50 years and foreign-born status were also associated with an increased risk of TF. No differences in TF according to sex at birth were found. By 3 years the probabilities of TD and VF were 13.4% (95% CI: 9.1%-17.6%) and 2.3% (95% CI: 0.19%-4.4%), respectively.</p><p><strong>Conclusions: </strong>In our real-world setting, the TF probability for first-line lamivudine/dolutegravir was below 6% at 3 years, lower than in randomized trials. Our data suggest that, as shown with other regimens, PWH starting lamivudine/dolutegravir with CD4 count of ≤200 cells/mm3, HIV-RNA of >100 000 copies/mL, older age or foreign-born status may be at higher risk of TF, though larger studies are needed to qualify the magnitude of the effect.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124934","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":"Phenotype-genotype discordance in antimicrobial resistance profiles of Gram-negative uropathogens recovered from catheter-associated urinary tract infections in Egypt.","authors":"Mohamed Eladawy, Nathan Heslop, David Negus, Jonathan C Thomas, Lesley Hoyles","doi":"10.1093/jac/dkaf352","DOIUrl":"https://doi.org/10.1093/jac/dkaf352","url":null,"abstract":"<p><strong>Objectives: </strong>Catheter-associated urinary tract infections (CAUTIs) are among the most common healthcare-associated infections in low- and middle-income countries (LMICs), but there are few resistome data available for relevant uropathogens. The goal of this study was to characterize the antimicrobial resistance (AMR) phenotypes and genotypes of a large collection of Gram-negative bacteria recovered from CAUTIs in a hospital in Mansoura, Egypt.</p><p><strong>Methods: </strong>Phenotypic AMR profiles and whole-genome sequence data were generated for 132 isolates. Resistomes were predicted using ResFinder, CARD and AMRFinder. Similarity of uropathogen genomic data was determined using sourmash (kmer signatures). Escherichia coli genomic data were subject to a pangenome analysis using Panaroo.</p><p><strong>Results: </strong>Sixty-seven E. coli (Phylogroup B2; 53.7%, 36/67), 14 Pseudomonas aeruginosa, 11 Klebsiella pneumoniae, 9 Proteus mirabilis, 8 Providencia spp., 5 Enterobacter hormaechei and 18 rare CAUTI-associated isolates were identified. Several (22/132) isolates were multidrug-resistant, while almost half (62/132) were extensively drug-resistant. Phenotype-genotype discordance was found to be an important consideration in resistome studies in Egypt, with a total concordance of 91% (1115/1225), 85.7% (1273/1485) and 80.5% (1196/1485) for ResFinder, CARD and AMRFinder, respectively. Pseudomonas, at the species level, exhibited the greatest discordance. At the antimicrobial level, meropenem was subject to greatest discordance. New AMR variants were found for Egypt for Pseudomonas (blaOXA-486, blaOXA-488, blaOXA-905, blaIMP-43, blaPDC-35, blaPDC-45, blaPDC-201) and E. coli (blaTEM-176, blaTEM-190).</p><p><strong>Conclusions: </strong>This study shows that there is phenotype-genotype discordance in AMR profiling among CAUTI isolates, highlighting the need for comprehensive approaches in resistome studies. We also show the genomic diversity of Gram-negative uropathogens contributing to disease burden in a little-studied LMIC setting.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124896","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":"Co-existence of the oxazolidinone resistance genes cfr and optrA on a novel multiresistance plasmid from a methicillin-resistant Macrococcoides bohemicum strain.","authors":"Yao Zhu, Susu Du, Stefan Schwarz, Jie Hou, Qiu Xu, Longhua Lin, Jiyun Chai, Caiping Ma, Hongfei Sun, Shuangyu Xie, Yongshan Song, Wanjiang Zhang","doi":"10.1093/jac/dkaf333","DOIUrl":"https://doi.org/10.1093/jac/dkaf333","url":null,"abstract":"<p><strong>Objectives: </strong>To identify and characterize the oxazolidinone resistance genes cfr and optrA from a methicillin-resistant Macrococcoides bohemicum strain of chicken origin.</p><p><strong>Methods: </strong>The presence of mobile oxazolidinone resistance genes was detected by PCR. Antimicrobial susceptibility testing was conducted by broth microdilution. Transfer experiments were carried out to evaluate horizontal transferability of the plasmid. WGS was performed using a combination of Illumina NovaSeq/Oxford Nanopore PromethION platforms.</p><p><strong>Results: </strong>The M. bohemicum strain HLJ23 exhibited an MDR phenotype and was positive for both cfr and optrA genes. WGS revealed that the genes cfr and optrA co-exist on the novel MDR plasmid pHLJ23-71kb. Although conjugation experiments were unsuccessful, plasmid pHLJ23-71kb could be transferred to Staphylococcus aureus RN4220 by electrotransformation. Genetic context analysis showed that the cfr and optrA together with another four antimicrobial resistance genes are located in an MDR region on plasmid pHLJ23-71kb. Sequence analysis suggested that this MDR region possibly originated from Mammaliicoccus or Staphylococcus spp.</p><p><strong>Conclusions: </strong>To the best of our knowledge, this study represents the first report of the oxazolidinone resistance genes cfr and optrA in the genus Macrococcoides. Furthermore, attention should be paid to the exchange of resistance determinants between members of the genera Staphylococcus, Mammaliicoccus and Macrococcoides.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112836","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":"Eligibility and factors associated with long-acting injectable cabotegravir-rilpivirine initiation in an urban academic HIV clinic.","authors":"Geoffroy Liegeon, Eleanor Friedman, Christopher Kaperak, Paul Djuricich, Alicia Dawdani, Sophie Plotkin, Jessica Schmitt, Aniruddha Hazra, Katerina A Christopoulos, John A Schneider, Moira C McNulty","doi":"10.1093/jac/dkaf346","DOIUrl":"https://doi.org/10.1093/jac/dkaf346","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to assess eligibility for long-acting injectable (LAI) cabotegravir/rilpivirine among people with HIV (PWH), identify factors associated with initiation and examine provider prescribing patterns in an urban academic clinic in the USA.</p><p><strong>Patients and methods: </strong>We conducted a retrospective cohort analysis among PWH at the University of Chicago HIV clinic from 1 January 2021 to 31 May 2023. Eligibility criteria for LAI cabotegravir/rilpivirine included HIV-1 RNA <50 copies/mL for ≥3 months, no active hepatitis B, no resistance to rilpivirine or cabotegravir and no treatment failure history. Logistic regression identified factors associated with initiation among eligible PWH as well as prescribing patterns of providers.</p><p><strong>Results: </strong>Of 657 PWH, 413 (63%) were eligible for LAI cabotegravir/rilpivirine. Median age was 45, 33% were women, 84% Black, 70% had permanent housing, 52% employed, 56% on Medicaid, 9% had active substance use and 26% had psychiatric comorbidities. Among those eligible, 64 PWH (15%) initiated LAI cabotegravir/rilpivirine. In multivariate analysis, younger age was the only factor associated with LAI cabotegravir/rilpivirine initiation [OR 0.96, 95% CI (0.94, 0.99), P = 0.01]. Prescribing patterns varied widely among the 13 providers, with initiation rates ranging from 0% to 33% (P < 0.001). Two providers, covering 40% of eligible patients, were responsible for 70% of initiations.</p><p><strong>Conclusions: </strong>In our urban HIV clinic, 63% of PWH were eligible for LAI cabotegravir/rilpivirine, and 15% initiated it within 2.5 years post-approval. Age and provider patterns significantly influenced LAI cabotegravir/rilpivirine uptake. Understanding factors driving LAI cabotegravir/rilpivirine uptake is key to expanding its reach.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113033","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":"Potential human health risk of carbapenem-non-susceptible Pseudomonas aeruginosa from companion animals.","authors":"Jirachaya Toyting-Hiraishi, Toyotaka Sato, Mana Tohyama, Taro Fujino, Kaho Okada, Kazuyoshi Sasaoka, Nozomu Yokoyama, Kana Torii, Akio Suzuki, Yuzo Tsuyuki, Kensuke Nakamura, Mitsuyoshi Takiguchi, Motohiro Horiuchi","doi":"10.1093/jac/dkaf338","DOIUrl":"https://doi.org/10.1093/jac/dkaf338","url":null,"abstract":"<p><strong>Background and objectives: </strong>The close bond between companion animals and humans may accelerate the spread of antimicrobial-resistant bacteria. Pseudomonas aeruginosa, an opportunistic pathogen in both, poses a public health threat due to antimicrobial resistance (AMR) and diverse virulence factors. However, One Health-based comparison remains limited. This study investigated the current AMR status and molecular characteristics of P. aeruginosa in companion animals in Japan to assess potential human health risks.</p><p><strong>Methods: </strong>We examined 197 P. aeruginosa clinical isolates from companion animals [dogs (n = 99) and cats (n = 98)] across Japan in 2024. Antimicrobial susceptibility to human clinical antibiotics was evaluated. In carbapenem-non-susceptible isolates, multilocus sequence typing and detection of resistance genes and virulence factors were performed.</p><p><strong>Results: </strong>Ciprofloxacin (20.3%) and piperacillin (10.7%) showed the highest resistance rates, with 5.6% of isolates being multidrug-resistant. Carbapenem resistance rates were 6.1% for imipenem and 1.0% for meropenem. Thirty-five isolates (17.8%) exhibited carbapenem non-susceptibility but remained susceptible to cefepime, ciprofloxacin, or amikacin. Of 27 identified sequence types, 20 (77.1% of carbapenem-non-susceptible isolates) were known in humans, including two high-risk clones (ST233 and ST298; 8.6%) reported for the first time in Japanese companion animals. These isolates carried mutations in efflux pump-related genes and multiple virulence factors. One showed close genetic relatedness to a human isolate, suggesting possible interspecies transmission.</p><p><strong>Conclusions: </strong>Our findings highlight the potential cross-species transmission risk of antimicrobial-resistant P. aeruginosa. Identification of shared high-risk clones with multiple virulence factors emphasizes the need for continuous vigilance and actions within the One Health framework.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091804","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":"Novel multiresistance transposon Tn7731 in bovine Pasteurella multocida from Germany.","authors":"Henrike Krüger-Haker, Dennis Hanke, Stefan Fiedler, Heike Kaspar, Stefan Schwarz","doi":"10.1093/jac/dkaf336","DOIUrl":"https://doi.org/10.1093/jac/dkaf336","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091793","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":"Rapid replacement of blaKPC variant in ST11 carbapenem-resistant and hypervirulent Klebsiella pneumoniae contributed to ceftazidime/avibactam resistance during severe in vivo infection.","authors":"Ping Yang, Chao Liu, Jiajia Zheng, Juan Yi, Zhenchao Wu, Yun Tian, Pengcheng Du, Ming Lu, Ning Shen","doi":"10.1093/jac/dkaf337","DOIUrl":"https://doi.org/10.1093/jac/dkaf337","url":null,"abstract":"<p><strong>Objectives: </strong>Hypervirulent ceftazidime/avibactam (CAZ/AVI)-resistant Klebsiella pneumoniae (Kp) has emerged; however, its dynamic within-host evolution and competitive features are uncharacterized. This study aimed to clarify the systematic microevolution characteristics of the rapid transformation of blaKPC variants during long-term infection.</p><p><strong>Methods: </strong>Thirty-nine Kp strains were isolated from a single patient with severe recurrent osteomyelitis during a 2-year period. Whole-genome sequencing and in vitro evolution assay was performed. Microbiological characteristics were examined through antimicrobial susceptibility testing, plasmid stability, growth curve, in vitro competition and Galleria mellonella larvae lethality assays.</p><p><strong>Results: </strong>Among all the clinical Kp isolates, 37 were carbapenem-resistant Kp (CRKP), including 25 CAZ-/AVI-resistant Kp. All isolates belonged to the ST11-K47. During in vivo evolution, the blaKPC variant and its amplification emerged. Twenty-four isolates (24/39, 61.5%) harboured a novel blaKPC variant, blaKPC-144. All five Kp isolates carried blaKPC-2 in 2021. Surprisingly, 24 blaKPC-144-harbouring isolates (70.6%, 24/34) and 10 blaKPC-2-harboring isolates were identified in 2023, indicating rapid changing of blaKPC. Kp4 carried two copies of blaKPC-2, and Kp10-1 exhibited a 1.94-fold increase in the blaKPC-144 copy number. Similarly, in vitro, the blaKPC copy number increased upon exposure to low CAZ/AVI concentrations. However, at higher concentrations (4/1 mg/L), the blaKPC copy number increased significantly, and blaKPC mutations emerged simultaneously. The competition assay indicated that the blaKPC-144-harboring isolates exhibited a superior competitive capacity.</p><p><strong>Conclusions: </strong>The blaKPC amplification and mutation emerged simultaneously or sequentially during in vivo and in vitro evolution. Kp isolates harbouring blaKPC-144, conferring resistance to CAZ/AVI, exhibited a competitive advantage, promoting the rapid replacement of blaKPC-2.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091751","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}