International Journal of Antimicrobial Agents最新文献

{"title":"Enhancing meropenem therapy in critical care: A retrospective study of PK/PD target attainment and therapeutic drug monitoring","authors":"Jingli Liao , Chao Li , Jingxian Liu , Wei Wu , Xiaohui Huang , Yanfei Mao , Lixia Li","doi":"10.1016/j.ijantimicag.2025.107697","DOIUrl":"10.1016/j.ijantimicag.2025.107697","url":null,"abstract":"<div><h3>Background</h3><div>Meropenem is a first-line treatment for severe infections; however, its efficacy is increasingly compromised by drug resistance. This situation underscores the urgent need to optimise dosing strategies and establish precise efficacy evaluation systems.</div></div><div><h3>Objectives</h3><div>This study aimed to evaluate the adequacy of the initial meropenem regimen by analysing factors associated with its clinical efficacy in critically ill patients, as well as to define predictive pharmacokinetic/pharmacodynamic (PK/PD) targets.</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis of 205 critically ill patients treated with meropenem. Logistic regression was employed to analyse factors influencing clinical efficacy and bacterial clearance rates, while Cox regression was utilised to assess factors affecting 30-d mortality. Receiver operating characteristic (ROC) analysis was performed to identify PK/PD targets using the first therapeutic drug monitoring (TDM) serum concentrations, and assessed the predictive performance of trough (C<sub>min</sub>) and peak (C<sub>max</sub>) concentrations concerning clinical efficacy.</div></div><div><h3>Results</h3><div>The clinical effectiveness of meropenem in critically ill patients was found to be 56.6%. Independent risk factors affecting clinical efficacy included C<sub>min</sub> (< 6 mg/L vs. ≥ 6 mg/L), urinary tract infections, tigecycline combination therapy, meropenem-sensitive vs. meropenem-resistant pathogens, sequential organ failure assessment (SOFA) scores (2–5 vs. > 5), and neutrophil counts. Notably, patients receiving prolonged infusion (≥ 2 h) achieved both significantly higher meropenem trough concentrations and better clinical efficacy than those on intermittent infusion. The bacterial clearance rate was 39.0%, which was associated with C<sub>min</sub> (< 8 mg/L vs. ≥ 8 mg/L) and the presence of meropenem-sensitive vs. resistant bacteria. The 30-d mortality rate was 20.0%, linked to age, pulmonary infections, tigecycline combination therapy, surgical history, hospital stay duration, and sequential organ failure assessment (SOFA) scores. Optimal efficacy was achieved with C<sub>min</sub> ≥ 5.3 mg/L and C<sub>max</sub> ≥ 39.4 mg/L, with higher thresholds required for bloodstream infections (C<sub>min</sub> ≥ 7.3 mg/L; C<sub>max</sub> ≥ 49.1 mg/L).</div></div><div><h3>Conclusion</h3><div>Meropenem demonstrates significant efficacy against severe infections caused by sensitive pathogens, particularly in cases of urinary tract infections. We identified that a C<sub>min</sub> of ≥ 5.3 mg/L and a C<sub>max</sub> of ≥ 39.4 mg/L are associated with optimal clinical efficacy. Based on these findings, we propose an initial dosing strategy tailored to renal function and the site of infection. Our results underscore the value of early TDM in identifying patients at risk of suboptimal exposure, which provides a crucial foundation for subsequent do","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107697"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843619","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":"Comments on ‘Acute kidney injury associated with colistin sulphate vs. polymyxin B sulphate therapy: A real-world, retrospective cohort study’","authors":"Genzhu Wang","doi":"10.1016/j.ijantimicag.2025.107702","DOIUrl":"10.1016/j.ijantimicag.2025.107702","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107702"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843534","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":"Clinical outcomes of metronidazole dosing strategies in obese patients with Bacteroides bloodstream infections","authors":"Sunish Shah , Rachel V. Marini , Dayna McManus , Ryan K. Shields , Jeffrey E. Topal , Tyler Tate","doi":"10.1016/j.ijantimicag.2025.107701","DOIUrl":"10.1016/j.ijantimicag.2025.107701","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107701"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846608","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":"Risk of infective endocarditis in oncohaematological patients undergoing active treatment with Enterococcus faecalis bloodstream infection: A retrospective multicentre study","authors":"Miguel Ángel Consuegra Pérez ,&nbsp;Sara Grillo ,&nbsp;Alexander Rombauts ,&nbsp;María Alba Rivera Martínez ,&nbsp;Anna Falcó-Roget ,&nbsp;Adaia Albasanz-Puig ,&nbsp;Belén Viñado-Pérez ,&nbsp;Nuria Fernández-Hidalgo ,&nbsp;Laura Camps-Relats ,&nbsp;Alba Bergas ,&nbsp;Julia Laporte-Amargos ,&nbsp;Joaquín López-Contreras ,&nbsp;Laura Escolà-Vergé","doi":"10.1016/j.ijantimicag.2025.107706","DOIUrl":"10.1016/j.ijantimicag.2025.107706","url":null,"abstract":"<div><h3>Objectives</h3><div><em>Enterococcus faecalis</em> bloodstream infections (EF-BSIs) are a common cause of infective endocarditis (IE). Recent guidelines consider <em>E. faecalis</em> bacteraemia a major criterion for IE and recommend systematic echocardiographic screening. The objective of this study was to describe the risk of IE in patients with an EF-BSI and an active oncohaematological malignancy.</div></div><div><h3>Methods</h3><div>We conducted a retrospective multicentre cohort study across three cancer centres in Barcelona, Spain, including all consecutive adults with EF-BSI and active oncohaematological malignancy who had received oncologic treatment within the previous 3 months from January 2014 to December 2023. Patients were identified via microbiology databases. The primary outcome was a diagnosis of definite IE based on European Society of Cardiology criteria. Secondary outcomes included 30-d mortality, 6-month relapse, and cumulative mortality.</div></div><div><h3>Results</h3><div>A total of 148 patients were included (median age 64.5 y [IQR 57–72]; 53% male). Eighty (54%) patients had a haematological malignancy, and 68 (46%) a solid tumour. Prosthetic heart valves were present in 4 (3%) patients. Most common BSI sources were primary (39, 26%), urinary tract (36, 24%), abdominal or biliary tract (36, 24%), and central venous catheter-related infections (33, 22%). Echocardiography was performed in 22 patients (15%), with only 2 (1%) diagnosed with definite IE: one had a prosthetic valve, and both had persistent bacteraemia. The 30-d mortality rate was 29% and the 6-month cumulative mortality was 55%. Six patients (7%) experienced relapse, with no new IE diagnoses.</div></div><div><h3>Conclusions</h3><div>Systematic IE screening may not be warranted in this population and should instead be individualised on the basis of clinical risk factors.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107706"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850087","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":"Ceftazidime/avibactam and ceftolozane/tazobactam for severe paediatric infections: A systematic review, meta-analysis, and evidence map","authors":"Paula Pimenta-de-Souza ,&nbsp;Alice Ramos-Silva ,&nbsp;Valcieny Sandes ,&nbsp;Patrícia Portella ,&nbsp;Thaís Gouvêa ,&nbsp;Fernando Fernandez-Llimos ,&nbsp;Elisangela Costa Lima","doi":"10.1016/j.ijantimicag.2025.107710","DOIUrl":"10.1016/j.ijantimicag.2025.107710","url":null,"abstract":"<div><h3>Background</h3><div>The growing prevalence of multidrug-resistant Gram-negative bacilli poses major challenges to the management of severe paediatric infections. Ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T) are newer β-lactam/β-lactamase inhibitor combinations with established efficacy in adults.</div></div><div><h3>Objective</h3><div>To synthesize current evidence on the efficacy, effectiveness, and safety of CZA and C/T in hospitalized children with severe infections.</div></div><div><h3>Methods</h3><div>We conducted a systematic review, meta-analysis, and evidence map (PROSPERO CRD420251025715). Searches were performed in PubMed, Scopus, CENTRAL, Epistemonikos, LILACS, SciELO, and Web of Science. Eligible designs included randomized controlled trials (RCTs), cohort studies, case series, and case reports evaluating CZA or C/T for complicated intra-abdominal infections, complicated urinary tract infections (cUTI), pneumonia, or bacteraemia in patients aged 0–18 y. The primary outcome was 30-d mortality; secondary outcomes were clinical and microbiological cure and adverse events.</div></div><div><h3>Results</h3><div>Nineteen studies (4 RCTs, 9 case series, 6 case reports) involving 472 patients were included. Sixteen studies evaluated CZA and three evaluated C/T. All RCTs were phase II, industry-sponsored, and excluded critically ill children and carbapenem-resistant infections. According to the updated RoB 2 assessment, two trials had overall low risk of bias, and two presented some concerns, mainly related to missing outcome data. No deaths occurred in RCTs, whereas observational studies reported 8% mortality. Clinical and microbiological cure exceeded 80% across study designs. Adverse events were generally infrequent; neonatal events clustered in case series, but evidence was insufficient for statistical comparison across age groups. Certainty of evidence ranged from moderate (cUTI with susceptible pathogens) to very low (pneumonia and resistant infections).</div></div><div><h3>Conclusions</h3><div>CZA and C/T appear promising for paediatric cUTI and complicated intra-abdominal infections, but the evidence base remains narrow and largely dependent on small, industry-funded trials. Independent RCTs including critically ill children and resistant infections are urgently needed.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107710"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905589","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":"Title Page & Editorial Board","authors":"","doi":"10.1016/S0924-8579(26)00016-6","DOIUrl":"10.1016/S0924-8579(26)00016-6","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107727"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189071","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":"Vancomycin clearance compared to creatinine clearance by timed urine collection in the intensive care unit","authors":"Andrew Chantha Hean ,&nbsp;Rinoj Mathew ,&nbsp;Frank Chu ,&nbsp;Linda Awdishu","doi":"10.1016/j.ijantimicag.2025.107704","DOIUrl":"10.1016/j.ijantimicag.2025.107704","url":null,"abstract":"<div><h3>Objective</h3><div>Prior literature elucidating the ratio of vancomycin clearance by the kidneys to creatinine clearance is conflicting. Further studies are warranted evaluating vancomycin clearance, especially in the critically ill population.</div></div><div><h3>Methods</h3><div>This retrospective exploratory analysis includes data from a decade of pulmonary/medical or cardiac ICU admissions where a serum creatinine, vancomycin concentration, and 24-hour timed urine collection were obtained within a 72-hour period. Patients with dialysis prior to, or 48 hours after, urine collection were excluded. The primary outcome was the ratio of vancomycin clearance (CLv) to creatinine clearance measured by timed urine collection (mCLcr). Exploratory outcomes also included (1) P30 accuracy and bias of CLv, BSA adjusted 2021 CKD-Epidemiology Collaboration (EPI) creatinine eGFR, Jelliffe creatinine clearance, and Cockcroft-Gault creatinine clearance equations when compared to mCLcr; (2) the correlations of clearances to mCLcr; and (3) the number of patients with augmented renal clearance for each kidney function estimating equation.</div></div><div><h3>Results</h3><div>A total of 56 eligible subjects were analysed. The ratio of CLv to mCLcr was 0.64. Although CLv showed the lowest P30 accuracy, it was the most correlated with mCLcr along with the 2021 CKD-EPI creatinine eGFR to mCLcr.</div></div><div><h3>Conclusions</h3><div>In critically ill patients who warrant medical, pulmonary, or cardiac ICU admission, the ratio of total vancomycin clearance to mCLcr measured by timed urine collection may differ from other populations. CLv and the 2021 CKD-EPI creatinine equation may be more correlated to mCLcr by timed urine collection. Larger studies are needed to confirm these results.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107704"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850061","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":"EnvZ mutation–driven downregulation of catecholate siderophore receptors and concurrent TonB complex repression confer cefiderocol resistance in a KPC-producing ST11-KL64 hypervirulent Klebsiella pneumoniae","authors":"Danni Pu ,&nbsp;Xianxia Zhuo ,&nbsp;Rongrong Song ,&nbsp;Chunhui Wang ,&nbsp;Jiankang Zhao ,&nbsp;Bin Cao","doi":"10.1016/j.ijantimicag.2025.107693","DOIUrl":"10.1016/j.ijantimicag.2025.107693","url":null,"abstract":"<div><h3>Objectives</h3><div>Cefiderocol is an ultimate antibiotic option for Carbapenem-resistant hypervirulent <em>Klebsiella pneumoniae</em> (CR-hvKP). While resistance often involves metallo-β-lactamases, mechanisms in KPC-producing strains are unclear. This study aimed to elucidate novel cefiderocol resistance mechanisms in a clinical KPC-producing ST11-KL64 CR-hvKP isolate.</div></div><div><h3>Methods</h3><div>Cefiderocol-resistant mutants were generated through <em>in vitro</em> experimental evolution. Resistance-associated mutations were identified by whole-genome sequencing. Transcriptomic and proteomic analyses were performed to characterize global regulatory changes and were validated by qRT-PCR and targeted genetic manipulation. Additional tests examined siderophore production, intracellular iron levels, bacterial fitness, oxidative stress tolerance, and macrophage survival.</div></div><div><h3>Results</h3><div>All high-level cefiderocol-resistant mutants acquired a gain-of-function mutation in the sensor kinase EnvZ (V145G). Integrated transcriptomic and proteomic analyses showed that the <em>envZ</em> mutation drove marked downregulation of catecholate siderophore receptors (<em>cirA</em> and <em>fepA</em>), impairing cefiderocol uptake. In parallel, the TonB–ExbB–ExbD energy transduction complex was independently and stably downregulated, synergistically contributing to resistance. Notably, <em>envZ</em> mutation–associated repression of the enterobactin biosynthesis gene <em>entB</em> paradoxically increased cefiderocol susceptibility, indicating a regulatory trade-off. Resistant mutants exhibited reduced siderophore production, impaired intracellular iron accumulation, and significant fitness costs, including attenuated growth, reduced oxidative stress tolerance, and decreased survival within macrophages.</div></div><div><h3>Conclusions</h3><div>In conclusion, this work uncovers a novel cefiderocol resistance mechanism in KPC-producing ST11-KL64 CR-hvKp, initiated by the <em>envZ</em> mutation, which causes the downregulation of catecholate siderophore receptors. This receptor repression, combined with the stable downregulation of the TonB-ExbB-ExbD energy complex, severely impairs cefiderocol's “Trojan horse” active uptake. This resistance mechanism is accompanied by a fitness trade-off, providing critical insights into the evolution of these superbugs.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107693"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800434","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":"Formation of a novel multiresistance plasmid co-carrying tigecycline, carbapenem, and other resistance genes by recombination during conjugative transfer in Klebsiella pneumoniae","authors":"Runhao Yu ,&nbsp;Zhong Chen ,&nbsp;Stefan Schwarz ,&nbsp;Hong Yao ,&nbsp;Chenglong Li ,&nbsp;Xiang-Dang Du","doi":"10.1016/j.ijantimicag.2025.107683","DOIUrl":"10.1016/j.ijantimicag.2025.107683","url":null,"abstract":"<div><h3>Objective</h3><div><em>Klebsiella pneumoniae</em> is a major global nosocomial pathogen, and strains acquiring extended-spectrum β-lactamase (ESBL) or carbapenemase resistance genes exhibit extensive clinical drug resistance, posing a serious public health threat. This study aimed to characterize the genetic features and transferability of resistance determinants in a clinically isolated multidrug-resistant <em>K. pneumoniae</em> strain.</div></div><div><h3>Methods</h3><div>A multidrug-resistant <em>K. pneumoniae</em> strain was isolated from clinical samples. Whole-genome sequencing was performed to identify the resistance genes carried by the strain and the transposase sequences within the genetic environment of the target resistance genes. Conjugative transfer experiments were conducted to verify the transferability of the identified resistance genes and their genetic recombination characteristics.</div></div><div><h3>Results</h3><div>The clinical isolate was confirmed to co-carry a <em>tet</em>(A) variant, <em>tmexCD2-toprJ2</em>, and <em>bla</em>_NDM-1 resistance genes. Whole-genome sequencing revealed the presence of IS<em>26</em>, IS<em>3000</em>, and ∆<em>tnpA</em> transposase sequences in the genetic environment of <em>tet</em>(A)v and <em>bla</em>_NDM-1 genes. Conjugative transfer experiments verified the transferability of the different resistance genes, and notably, recombination and co-transfer events of <em>tet</em>(A)v and <em>bla</em>_NDM-1 genes were detected within the conjugative plasmid of the strain.</div></div><div><h3>Conclusions</h3><div>Transposases play a crucial role in the formation of complex multidrug-resistant <em>K. pneumoniae</em> strains. The findings of this study provide a novel perspective and critical evidence for elucidating the antimicrobial resistance mechanisms and dissemination pathways of multidrug-resistant <em>K. pneumoniae</em>.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107683"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654199","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":"ATP-binding cassette transporters mediate and regulate metronidazole resistance in Clostridioides difficile","authors":"Teng Xu ,&nbsp;Ying Zhou ,&nbsp;Qingqing Xu ,&nbsp;Li Wang ,&nbsp;Yu Zhou ,&nbsp;Shi Wu ,&nbsp;Haihui Huang","doi":"10.1016/j.ijantimicag.2025.107709","DOIUrl":"10.1016/j.ijantimicag.2025.107709","url":null,"abstract":"<div><h3>Objective</h3><div>Metronidazole (MTZ) resistance in <em>Clostridioides difficile</em> is associated with decreased efficacy of MTZ. We studied the MTZ-resistant <em>C. difficile</em> strain sh182IR (minimum inhibitory concentration [MIC] = 32 mg/L) to characterize the role of ATP-binding cassette (ABC) family transporters in MTZ resistance in <em>C. difficile</em>. The strain overexpresses ABC multidrug efflux pump components.</div></div><div><h3>Methods</h3><div>In strain sh182IR, ClosTron mutagenesis was applied to disrupt <em>cd17530</em>, a gene encoding the ABC transporter ATP-binding protein, and the effects on efflux capacity and MIC of MTZ were evaluated. The upstream regulatory gene <em>cd17520</em> was also sequenced.</div></div><div><h3>Results</h3><div>Disruption of <em>cd17530</em> reduced the efflux capacity of fluorescent substrates and MIC of MTZ in <em>C. difficile</em> sh182IR. Repair of <em>cd17530</em> successfully restored the MTZ MIC and efflux capacity of the strain. We also confirmed that the upstream TetR/AcrR family transcription factor gene <em>cd17520</em> in sh182IR harbours a frameshift mutation. This mutation resulted in the loss of function of the peptide chain encoded by the gene and upregulation of cd17530-17540-17550.</div></div><div><h3>Conclusions</h3><div>The frameshift mutation in the transcriptional repressor <em>cd17520</em>, which results in the derepression of the cd17530-17540-17550 operon, contributes to ABC transporter-mediated MTZ resistance in <em>C. difficile</em>.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107709"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905677","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}