Journal of Antimicrobial Chemotherapy最新文献

{"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}

{"title":"Multidrug resistance and recurrence in urinary bacteraemia among cancer patients.","authors":"Ignacio Grafia, Alba Moll-Febrer, Solanche Jasmin Santillán, Clara Rodrigo, Eva Lillo, Néstor López, Berta Fidalgo, Verónica Rico-Caballero, Mateu Espasa-Soley, Daniel N Marco, Cristina Pitart, Javier Marco-Hernández, Sara Fernández, Carles Zamora, Joan Padrosa, Marta Garcia de Herreros, Sabina Herrera, Margarita Viladot, Josep Mensa, Lucía Llavata, Albert Tuca, Alex Soriano, Pedro Puerta-Alcalde","doi":"10.1093/jac/dkaf335","DOIUrl":"https://doi.org/10.1093/jac/dkaf335","url":null,"abstract":"<p><strong>Background: </strong>Urinary tract infections (UTI) in oncological patients can lead to bacteraemia (bUTI), increasing morbidity and mortality. This study assessed the characteristics, outcomes and recurrence of bUTI in oncological patients.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted at Hospital Clinic, Barcelona, from 2008 to 2019. All episodes of bUTI in oncological patients were analysed. Multivariable regression models identified independent risk factors for multidrug-resistant (MDR) Gram-negative bacilli (GNB), recurrent bUTI and related mortality.</p><p><strong>Results: </strong>A total of 561 bUTI episodes were identified in 478 oncological patients. Urinary tract involvement due to neoplasm was present in 62.2%, and 59.4% had urinary tract instrumentation. Prior UTI-related admission without bacteraemia was reported in 63.8%. Following bUTI, oncological treatment was delayed in 47% and stopped in 33.6% of cases. GNB caused 87.3% of episodes, with Escherichia coli and Klebsiella spp. being the most common pathogens. Enterococcus spp. and Pseudomonas aeruginosa were frequent, particularly in patients with urinary instrumentation. MDR-GNB caused 19.6% of episodes, and 23.4% of cases received inappropriate empirical antibiotic therapy (IEAT). Recurrent bUTI occurred in 14.0% of patients. A simple predictive score efficiently identified patients at high risk of recurrence. Thirty-day mortality was 15.3%, and bUTI-related mortality was 10.7%, with absence of fever, septic shock and carbapenemase-producing Enterobacterales linked to higher related mortality.</p><p><strong>Conclusion: </strong>bUTI in oncological patients is predominantly caused by GNB, with high rates of MDR isolates and high mortality. IEAT is common, and recurrence is significant, highlighting the need for targeted preventive strategies and optimized empirical therapy.</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":"145091756","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":"Pharmacokinetics of aztreonam/avibactam in a critically ill patient with a class B metallo-β-lactamase producing Enterobacteriaceae and receiving continuous renal replacement therapy.","authors":"Daniel Fresán, Maria Pilar Gracia-Arnillas, Aitor Iriarte Zugasti, Cristina Raich Gual, Carla Comajuán Mendoza, María Acer, Rosana Muñoz-Bermudez, María Milagro Montero, Luisa Sorlí, Sonia Luque","doi":"10.1093/jac/dkaf330","DOIUrl":"https://doi.org/10.1093/jac/dkaf330","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091802","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":"Azithromycin resistance in non-typhoidal Salmonella: a review.","authors":"Zhe Zhu, Xin Hua, Yefang Ke","doi":"10.1093/jac/dkaf341","DOIUrl":"https://doi.org/10.1093/jac/dkaf341","url":null,"abstract":"<p><p>Antibiotics are crucial for controlling severe or invasive non-typhoidal Salmonella (NTS) infections. However, the high resistance or toxicity of traditionally first-line antibiotics calls for alternatives. The excellent membrane permeability, long half-life and safe to use in children render azithromycin a promising candidate. However, azithromycin resistance has been observed in NTS isolates recovered from humans, food, animals and the environment, with particularly high rates in Asia. Although azithromycin resistance remains low in Europe, the USA and Australia, an increasing tendency has been noted in the USA in recent years. Macrolide inactivation by phosphotransferases, methylation of 23S rRNA by methyltransferases, ribosomal protein alteration and efflux pumps are involved in azithromycin resistance in NTS isolates, among which phosphotransferase encoded by the mph (A) gene is the predominate mechanism. Current studies face limitations, such as the lack of a standardized azithromycin breakpoint for NTS isolates, insufficient integrated national surveillance and limited robust clinical evidence for treating NTS infections. Therefore, future studies addressing these issues are highly recommended.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091722","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":"Molecular insights into carbapenemase-producing Enterobacterales from Senegal.","authors":"Ousmane Sow, Saoussen Oueslati, Issa Ndiaye, Océane Vanparis, Adja Bousso Gueye, Imene Mehidi, Elhadj Aly Niang, Abdoulaye Cisse, Babacar Ndiaye, Abdou Diop, Alexis Proust, Bissoume Sambe, Delphine Girlich, Laurent Dortet, Rémy A Bonnin, Abdoulaye Seck, Thierry Naas","doi":"10.1093/jac/dkaf328","DOIUrl":"https://doi.org/10.1093/jac/dkaf328","url":null,"abstract":"<p><strong>Background: </strong>Carbapenemase-producing Enterobacterales (CPE) are an urgent global health threat, especially in resource-limited countries. Here we determined the prevalence and the molecular characteristics of CPE isolated from infections in Dakar, Senegal.</p><p><strong>Method: </strong>From January 2019 to December 2020, Enterobacterales with reduced susceptibility to ertapenem (diameter < 25 mm) from infections were collected at the Pasteur Institute of Dakar. Carbapenemases were detected using biochemical and immunochromatographical assays. WGS was used to determine resistome, MLST, plasmids, virulence genes and genetic relatedness.</p><p><strong>Results: </strong>Of the 1045 Enterobacterales collected during the study period, 86 had a diameter around ertapenem of <25 mm (8%) and 19 were confirmed as CPE (2%). These included Escherichia coli (n = 6) [ST410 (n = 3), ST405 (n = 2) and ST2083], Enterobacter spp. (n = 6) [ST231 (n = 3), ST245, ST760 and ST960] and Klebsiella spp. (n = 5) (ST22, ST25, ST231, ST1535, ST4843), Citrobacter freundii ST22 (n = 1) and Citrobacter koseri with unknown ST (n = 1). blaOXA-48 (n = 7; 35%), blaOXA-181 (n = 7; 35%) and blaNDM-5 (n = 6; 30%) genes were identified. C. freundii ST22 harboured blaNDM-5, blaOXA-48 and blaCTX-M-15 genes. Some E. coli isolates belonging to the high-risk clone ST410 were closely related (<20 SNPs) to isolates recovered in France from patients returning from Senegal, suggesting transnational spread. In addition, 5/6 carbapenemase-producing E. coli isolates possessed a four amino acid insertion in PBP3, conferring reduced susceptibility to aztreonam/avibactam and cefiderocol.</p><p><strong>Conclusions: </strong>This study highlights the spread of NDM-5 and OXA-181 in Senegal, and reports the first co-occurrence of NDM-5 and OXA-48 in sub-Saharan Africa. The spread of CPE, especially in high-risk clones, underscores the urgent need for continued surveillance and targeted interventions.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro evolution provides insights into mechanisms of Mycoplasma genitalium resistance to moxifloxacin.","authors":"Teck-Phui Chua, Jose L Huaman, Jennifer Danielewski, Catriona S Bradshaw, Dorothy A Machalek, Michael J McDonald, Suzanne M Garland, Gerald L Murray","doi":"10.1093/jac/dkaf324","DOIUrl":"https://doi.org/10.1093/jac/dkaf324","url":null,"abstract":"<p><strong>Background: </strong>Current knowledge of Mycoplasma genitalium fluoroquinolone resistance is based on sequence analyses of clinical samples, an approach with limited scope. Many potential resistance mutations have been described but their impact on moxifloxacin efficacy is unclear.</p><p><strong>Objective: </strong>To investigate the impact of individual mutations on fluoroquinolone resistance through selection of moxifloxacin-resistant mutants in vitro.</p><p><strong>Methods: </strong>M. genitalium G37 was passaged sequentially in sub-inhibitory concentrations of moxifloxacin. MIC values were determined for moxifloxacin, sitafloxacin, levofloxacin and ciprofloxacin. Bacterial populations were profiled using amplicon sequencing.</p><p><strong>Results: </strong>Across three independent experiments, four moxifloxacin mutants were isolated, with mutations encoding the following protein sequence variations: (i) GyrA D99Y/ParE E468K, (ii) ParC S83I/GyrA D99Y/ParE E468K, (iii) ParC D87V/GyrB P462S and (iv) GyrA M95I/ParE E468dup. Moxifloxacin MICs were elevated 16- to 32-fold for mutants with a single GyrA or ParC variation, and 128-fold for the dual GyrA/ParC mutant. Sitafloxacin MICs were elevated but remained lower than moxifloxacin MICs. Mutations did not have a substantial impact on in vitro growth dynamics. Population analysis showed that multiple mutations attained detectable population-wide frequencies, with evidence of clonal interference dynamics, with a minority becoming fixed in the population.</p><p><strong>Conclusion: </strong>Mutations in multiple genes conferring fluoroquinolone resistance appeared with regularity in vitro. Findings of an additive effect for ParC/GyrA changes, and greater effectiveness of sitafloxacin against resistant bacteria compared with moxifloxacin, are both consistent with clinical data. Improved understanding of fluoroquinolone resistance will inform the development of diagnostic assays predicting fluoroquinolone susceptibility.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091728","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}