International Journal of Antimicrobial Agents最新文献

{"title":"Investigation of PhoP response regulator inhibition to overcome resistance in Gram-negative clinical bacteria","authors":"Chaimae Majdi , Valentin Duvauchelle , Mohamed Seghir , David Bénimélis , Catherine Dunyach-Remy , Jean Dessolin , Patrick Meffre , Zohra Benfodda","doi":"10.1016/j.ijantimicag.2024.107298","DOIUrl":"10.1016/j.ijantimicag.2024.107298","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 4","pages":"Article 107298"},"PeriodicalIF":4.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912535","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":"Beware of resistance to 2nd-generation integrase inhibitors: A systematic meta-analysis of HIV-1 integrase inhibitors resistance and drug resistance mutations","authors":"Shanshan Liu ,&nbsp;Defu Yuan ,&nbsp;Ying Zhou ,&nbsp;Bei Wang ,&nbsp;Haiyang Hu","doi":"10.1016/j.ijantimicag.2024.107294","DOIUrl":"10.1016/j.ijantimicag.2024.107294","url":null,"abstract":"<div><h3>Objective</h3><p>Assessing the prevalence of resistance and drug resistance mutations (DRMs) in HIV/AIDS patients towards integrase strand transfer inhibitors (INSTIs), particularly the 2nd-generation INSTIs, provides evidence for rational clinical drug use.</p></div><div><h3>Methods</h3><p>A systematic search was conducted on five databases to identify relevant literature reporting original data on INSTIs resistance. Meta-analyses, cumulative meta-analyses, subgroup analyses and meta-regression analyses were performed using selected models based on the results of heterogeneity tests.</p></div><div><h3>Results</h3><p>A total of 81 studies were included in this analysis. The prevalence of pre-treatment drug resistance (PDR) to 1st-generation INSTIs and 2nd-generation INSTIs were 0.41% (95% CI: 0.19%–0.70%) and 0.04% (95% CI: 0.00%–0.13%), respectively; and the prevalence of acquired drug resistance (ADR) were 7.60% (95% CI: 3.54%–12.92%) and 4.93% (95% CI: 1.78%–9.36%), respectively, and ADR showed an increasing and then decreasing time trend. The results of subgroup analyses showed differences in ADR to 2nd-generation INSTIs between regions and economic levels, with the highest ADR of 12.83% (95% CI: 3.24%–27.17%) in the European region. DRMs varied among HIV patients and reduced drug sensitivity to varying degrees.</p></div><div><h3>Conclusion</h3><p>The prevalence of PDR and DRMs in 2nd-generation INSTIs is currently low, but as the use of DTG-based ART expands, population-level drug resistance monitoring and individual-level genetic testing should be strengthened in order to maximise treatment efficacy. Additionally, attention should be paid to ADR to INSTIs to provide personalised treatments for HIV-infected patients.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 3","pages":"Article 107294"},"PeriodicalIF":4.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889092","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":"Immunomodulator AS101 restores colistin susceptibility of clinical colistin-resistant Escherichia coli and Klebsiella pneumoniae in vitro and in vivo","authors":"Haifeng Liu ,&nbsp;Ying Zhang ,&nbsp;Zeyong Zhong ,&nbsp;Yanchun Gong ,&nbsp;Pingting Yu ,&nbsp;Yuhan Yang ,&nbsp;Yichi Zhang ,&nbsp;Tieli Zhou ,&nbsp;Lijiang Chen","doi":"10.1016/j.ijantimicag.2024.107285","DOIUrl":"10.1016/j.ijantimicag.2024.107285","url":null,"abstract":"<div><h3>Objectives</h3><p>Colistin (COL) was once considered to be the last line of defence against multidrug-resistant bacteria belonging to the family <em>Enterobacteriaceae</em>. Due to the misuse of COL, COL-resistant (COL-R) <em>Enterobacteriaceae</em> have emerged. To address this clinical issue and combat COL resistance, novel approaches are urgently needed.</p></div><div><h3>Methods</h3><p>In this study, the in vitro and in vivo antimicrobial and antibiofilm effects of the immunomodulator AS101 were investigated in combination with COL against COL-R <em>Escherichia coli</em> (<em>E. coli</em>) and <em>Klebsiella pneumoniae</em> (<em>K. pneumoniae</em>).</p></div><div><h3>Results</h3><p>Checkerboard assay, time-kill assay, and scanning electron microscopy confirmed the in vitro antimicrobial phenotype, whereas, crystal violet staining and multidimensional confocal laser scanning microscopy with live/dead staining confirmed the antibiofilm capability of the combination therapy. Moreover, the <em>Galleria mellonella</em> infection model and the mouse infection model indicated the high in vivo efficacy of the combination therapy. Additionally, cytotoxicity experiments performed using human kidney-derived HK-2 cells and haemolysis assays performed using human erythrocytes collectively demonstrated safety at effective combination concentrations. Furthermore, quantification of the expression of inflammatory cytokines via enzyme-linked immunosorbent assay confirmed the anti-inflammatory advantage of combination therapy. At the mechanistic level, changes in outer and inner membrane permeability and accumulation of ROS levels, which might be potential mechanisms for synergistic antimicrobial effects.</p></div><div><h3>Conclusions</h3><p>This study found that AS101 can restore COL susceptibility in clinical COL-R <em>E. coli</em> and <em>K. pneumoniae</em> and also has synergistic antibiofilm and anti-inflammatory capabilities. This study provided a novel strategy to combat clinical infections caused by COL-R <em>E. coli</em> and <em>K. pneumoniae</em>.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 4","pages":"Article 107285"},"PeriodicalIF":4.9,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901684","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":"Is There Evidence on the Optimal Duration of Aminoglycoside Therapy in β-Lactam/Aminoglycoside Combination Regimens Used for the Treatment of Gram-Negative Bacterial Infections? A Systematic Review","authors":"Yalew M. Wale ,&nbsp;Jason A. Roberts ,&nbsp;Zenaw T. Wolie ,&nbsp;Fekade B. Sime","doi":"10.1016/j.ijantimicag.2024.107297","DOIUrl":"10.1016/j.ijantimicag.2024.107297","url":null,"abstract":"<div><h3>Background</h3><p>The optimal duration of therapy of aminoglycosides in combination regimens is expected to be different from that of monotherapy regimens, and shorter durations could help minimize toxicity without compromising efficacy. The aim of this review was to assess the evidence for the optimal duration of aminoglycosides in β-lactam/aminoglycoside combinations used for the treatment of Gram-negative bacterial infections.</p></div><div><h3>Materials and Methods</h3><p>PubMed, Cochrane, Embase, Scopus, Web of Science, and CINHAL databases were searched. Covidence software was used for article screening and management. Studies were included if they clearly reported the duration of therapy of aminoglycosides in β-lactam/aminoglycoside combinations used against Gram-negative bacteria. The protocol is registered with PROSPERO (CRD42023392709).</p></div><div><h3>Results</h3><p>A total of 45 β-lactam/aminoglycoside combination courses from 32 articles were evaluated. The duration of therapy of aminoglycosides in combinations regimens ranged from 1 to 14 days, varying with the type of infection treated. In half (51.1%; (23/45) of the combinations, aminoglycosides were administered for a duration ranging from 6 to 9 days. In 26.7% (12/45) of the combinations, the duration of aminoglycoside therapy was ≤ 5 days. In the remaining 22.2% (10/45) of these combinations, the aminoglycosides were administered for a duration of ≥ 10 days. Aminoglycosides were administered for a longer duration of 7-14 days in 12 (75%) of the 16 combination courses that induced toxicity.</p></div><div><h3>Conclusions</h3><p>Long duration of aminoglycoside use is associated with increased risk of toxicity. However, there is a lack of evidence on defining an optimal duration of aminoglycoside therapy in β-lactam/aminoglycoside combination regimens that ensures clinical efficacy outcomes whilst minimizing toxicity outcomes.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 4","pages":"Article 107297"},"PeriodicalIF":4.9,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0924857924002139/pdfft?md5=e4072c48a07c72a55ed158a4454b0d5f&pid=1-s2.0-S0924857924002139-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A metagenomics-based approach to decipher the resistome and mobilome of two seahorse species, Hippocampus barbouri and Hippocampus comes","authors":"Chinee S. Padasas-Adalla ,&nbsp;Rose Chinly Mae H. Ortega-Kindica ,&nbsp;Carlos O. Lomelí-Ortega ,&nbsp;Sharon Rose M. Tabugo ,&nbsp;José Luis Balcázar","doi":"10.1016/j.ijantimicag.2024.107296","DOIUrl":"10.1016/j.ijantimicag.2024.107296","url":null,"abstract":"<div><h3>Objective</h3><p>This study aimed to explore the abundance and diversity of antibiotic resistance genes (ARGs) in seahorses (<em>Hippocampus barbouri</em> and <em>Hippocampus comes</em>) and their surrounding environment.</p></div><div><h3>Methods</h3><p>A combination of shotgun metagenomics and bioinformatics was used to investigate the resistome of both seahorse species.</p></div><div><h3>Results</h3><p>The analyses demonstrated a higher abundance of ARGs in seahorse-associated microbiomes, particularly in skin and gut samples, compared to those from water and sediment. Interestingly, genes conferring multidrug resistance (e.g., <em>acrB, acrF, cpxA, msbA</em>, and <em>oqxB</em>) were highly prevalent in all samples, especially in skin and gut samples. High levels of genes conferring resistance to fluoroquinolones (e.g., <em>mfd</em> and <em>emrB</em>), β-lactam (e.g., <em>bla</em>_CMY-71, <em>bla</em>_OXA-55, and <em>penA</em>), aminocoumarin (e.g., <em>mdtB</em> and <em>mdtC</em>), and peptide antibiotics (<em>arnA, pmrE</em>, and <em>rosA</em>) were also observed in skin and gut samples. An enrichment of mobile genetic elements (MGEs) was also observed in the analysed samples, highlighting their potential role in facilitating the acquisition and spread of ARGs. In fact, the abundance of mobilisation (MOB) relaxases (e.g., MOBF, MOBP, MOBT, and MOBV) in gut and skin samples suggests a high potential for conjugation events.</p></div><div><h3>Conclusions</h3><p>The occurrence of ARGs and MGEs in seahorses and the surrounding environment raises concerns about their transmission to humans, either through direct contact or the consumption of contaminated seafood. To the best of our knowledge, this study represents the first comprehensive analysis of ARGs in seahorse-associated microbiomes, and its results emphasise the need for monitoring and controlling the spread of ARGs in environmental settings.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 3","pages":"Article 107296"},"PeriodicalIF":4.9,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889091","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":"Outcome of intravenous and inhaled polymyxin B treatment in patients with multidrug-resistant gram-negative bacterial pneumonia","authors":"Peili Ding,&nbsp;Hangyang Li,&nbsp;Yuyu Nan,&nbsp;Chengwei Liu,&nbsp;Guobin Wang,&nbsp;Hongliu Cai,&nbsp;Wenqiao Yu","doi":"10.1016/j.ijantimicag.2024.107293","DOIUrl":"10.1016/j.ijantimicag.2024.107293","url":null,"abstract":"<div><h3>Purpose</h3><p>The incidence of pneumonia caused by multidrug-resistant gram-negative bacteria (MDR GNB) is increasing, which imposes significant burden on public health. Inhalation combined with intravenous polymyxins has emerged as a viable treatment option. However, pharmacokinetic studies focusing on intravenous and inhaled polymyxin B (PMB) are limited.</p></div><div><h3>Methods</h3><p>This study included seven patients with MDR GNB-induced pneumonia who were treated with intravenous plus inhaled PMB from March 1 to November 30, 2022, in the intensive care unit of the First Affiliated Hospital of Zhejiang University School of Medicine. Clinical outcomes and therapeutic drug monitoring data of PMB in both plasma and epithelial lining fluid (ELF) were retrospectively reviewed.</p></div><div><h3>Results</h3><p>Median PMB concentrations in the ELF were 7.83 (0.72–66.5), 116.72 (17.37–571.26), 41.1 (3.69–133.78) and 33.82 (0.83–126.68) mg/L at 0, 2, 6 and 12 h, respectively, and were much higher than those detected in the serum. ELF concentrations of PMB at 0, 2, 6 and 12 h were higher than the minimum inhibitory concentrations of pathogens isolated from the patients. Steady-state concentrations of PMB in the plasma were &gt;2 mg/L in most patients. Of the patients, 57.14% were cured and 71.43% showed a favourable microbiological response. The incidence of side effects with PMB was low.</p></div><div><h3>Conclusions</h3><p>Inhaled plus intravenous PMB can achieve high ELF concentrations and favourable clinical outcomes without an increased adverse effect profile. This treatment approach appears promising for the treatment of patients with pneumonia caused by MDR-GNB.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 4","pages":"Article 107293"},"PeriodicalIF":4.9,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0924857924002097/pdfft?md5=f5d40d3bd84d97e2557e0ae2c63c073c&pid=1-s2.0-S0924857924002097-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mediastinitis caused by an NDM-1 Escherichia coli in a child with Dacron Sano shunt after pulmonary atresia with ventricular septal defect surgery treated with combination of aztreonam-avibactam","authors":"Vladimir L. Cousin ,&nbsp;Jordi Miatello ,&nbsp;Roberto Sierra ,&nbsp;Tornike Sologashvili ,&nbsp;Julie Wacker ,&nbsp;Diego O. Andrey ,&nbsp;Arnaud G. L'Huillier","doi":"10.1016/j.ijantimicag.2024.107295","DOIUrl":"10.1016/j.ijantimicag.2024.107295","url":null,"abstract":"<div><p>Carbapenem-resistant Enterobacterales are being reported increasingly and cause nosocomial infections, which may include postoperative mediastinitis. This paper reports a case of postoperative mediastinitis caused by an <em>Escherichia coli</em> NDM-1 carbapenemase producer in a 13-month-old boy with DiGeorge syndrome. The infection was managed with surgical debridement and antibiotherapy with aztreonam, ceftazidime-avibactam and IV fosfomycin for 6 weeks. The evolution was favourable, without relapse over 10 weeks of follow-up.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 4","pages":"Article 107295"},"PeriodicalIF":4.9,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0924857924002115/pdfft?md5=a30a86e041550c57e0c6d9292d6d1bfe&pid=1-s2.0-S0924857924002115-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of outpatient parenteral antimicrobial therapy: A systematic review and meta-analysis of randomized clinical trials","authors":"","doi":"10.1016/j.ijantimicag.2024.107263","DOIUrl":"10.1016/j.ijantimicag.2024.107263","url":null,"abstract":"<div><h3>Background</h3><p>Outpatient parenteral antimicrobial therapy (OPAT) offers an alternative to inpatient (hospital bed-based) treatment of infections that require intravenous administration of antimicrobials. This meta-analysis aimed to summarise the evidence available from randomised controlled trials (RCTs) regarding the efficacy and safety of OPAT compared to inpatient parenteral antimicrobial therapy.</p></div><div><h3>Methods</h3><p>We searched the Cochrane Library, MEDLINE, Embase, PubMed, and Web of Sciences databases for RCTs comparing outpatient versus inpatient parenteral antimicrobial therapy. We included studies without restrictions on language or publication year. Eligibility was reviewed independently by two assessors, and data extraction was cross validated. We evaluated bias risk via the Cochrane tool and determined the evidence certainty using GRADE. Meta-analysis was conducted using a random effects model. The protocol of this review was registered on PROSPERO (CRD42023460389).</p></div><div><h3>Result</h3><p>Thirteen RCTs, involving 1,310 participants were included. We found no difference in mortality (Risk Ratio [RR] 0.54, 95% Confidence Interval [CI] 0.23 to 1.26; <em>P</em> = 0.93), treatment failure (RR 1.0, CI 0.59 to 1.72; <em>P</em> = 0.99), adverse reaction related to antimicrobials (RR 0.89, CI 0.69 to 1.15; <em>P</em> = 0.38), and administration device (RR 0.58, CI 0.17 to 1.98; <em>P</em> = 0.87) between outpatient and inpatient parenteral antimicrobial therapy. The overall body of evidence had a low level of certainty.</p></div><div><h3>Conclusion</h3><p>Existing evidence suggests OPAT is a safe and effective alternative to inpatient treatment. Further RCTs are warranted for a thorough comparison of inpatient and outpatient parenteral antimicrobial therapy with a high level of certainty.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 2","pages":"Article 107263"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0924857924001808/pdfft?md5=3b0e10eacfe13a8a80d4fc9e57ac349f&pid=1-s2.0-S0924857924001808-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In reply to the Letter to the Editor regarding Intrathecal or intraventricular antimicrobial therapy for post-neurosurgical Gram-negative bacillary meningitis or ventriculitis: A systematic review and meta-analysis","authors":"","doi":"10.1016/j.ijantimicag.2024.107217","DOIUrl":"10.1016/j.ijantimicag.2024.107217","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 2","pages":"Article 107217"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141133273","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":"Mechanisms and fitness of ceftazidime/avibactam-resistant Klebsiella pneumoniae clinical strains in Taiwan","authors":"","doi":"10.1016/j.ijantimicag.2024.107244","DOIUrl":"10.1016/j.ijantimicag.2024.107244","url":null,"abstract":"<div><h3>Background</h3><p>Carbapenem-resistant <em>Klebsiella pneumoniae</em> (CRKP) infection is a global public health issue, and ceftazidime/avibactam is recommended by international guidelines as the preferred treatment for KPC- and OXA-48-producing CRKP. Since its introduction in Taiwan in 2019, ceftazidime/avibactam-resistant strains have emerged. Our aim is to investigate the mechanisms of ceftazidime/avibactam resistance in CRKP in Taiwan and study their associated fitness costs.</p></div><div><h3>Methods</h3><p>Ceftazidime/avibactam-resistant CRKP strains with exposure to ceftazidime/avibactam isolated from clinical specimens were consecutively collected at Taipei Veterans General Hospital in 2020. The serial strains exhibiting ceftazidime/avibactam-susceptible and ceftazidime/avibactam-resistant phenotypes isolated from the same patient were characterized using whole-genome sequencing and tested for their growth rates and competitive abilities.</p></div><div><h3>Results</h3><p>A total of 35 ceftazidime/avibactam-resistant CRKP strains were identified, with 20 being metallo-β-lactamase producers. Ten strains harboured KPC variants, exhibiting MIC for ceftazidime/avibactam ranging from 64 to ≥256 mg/L. The 10 strains demonstrating high-level ceftazidime/avibactam resistance possessed mutated KPC variants: KPC-33 (<em>n</em> = 3), KPC-31 (<em>n</em> = 1), KPC-39 (<em>n</em> = 1), KPC-44 (<em>n</em> = 1), KPC-58 (<em>n</em> = 1), KPC-90 (<em>n</em> = 1), and two novel KPC variants. Ceftazidime/avibactam-resistant strains with KPC-33 and KPC-39 showed a significant fitness cost and lower growth rate compared to their parental strains. In contrast, ceftazidime/avibactam-resistant strains with KPC-58 and KPC-58 plus D179Y showed similar growth rates and competitive abilities compared to their parental strains.</p></div><div><h3>Conclusions</h3><p>Mutated KPC variants conferred high-level ceftazidime/avibactam resistance in Taiwan. Significant fitness costs were observed in both the ceftazidime/avibactam-resistant KPC-33 and KPC-39 strains. Despite conferring a similar level of ceftazidime/avibactam resistance, different KPC variants could entail varying degrees of fitness costs.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 2","pages":"Article 107244"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456596","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}