Journal of global antimicrobial resistance最新文献

{"title":"Emergence of blaKPC-71 variant and loss of aerobactin-encoding genes (iucABCD-iutA) in ST11-K64 carbapenem-resistant Klebsiella pneumoniae during ceftazidime–avibactam treatment","authors":"Fang-ling Du ,&nbsp;Dan-dan Wei ,&nbsp;Yong-qing Guo ,&nbsp;Peng Liu ,&nbsp;Yan-fang Mei ,&nbsp;Shan-shan Huang ,&nbsp;Qi-sen Huang ,&nbsp;Lin-Ping Fan ,&nbsp;Yang Liu","doi":"10.1016/j.jgar.2025.11.020","DOIUrl":"10.1016/j.jgar.2025.11.020","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the within-host evolutionary dynamics of resistance and virulence in carbapenem-resistant <em>Klebsiella pneumoniae</em> during ceftazidime-avibactam treatment.</div></div><div><h3>Methods</h3><div>Three <em>K. pneumoniae</em> strains were isolated from the sputum of the same patient. Broth microdilution method, whole-genome sequencing and genetic analysis were employed to clarify the dynamics and mechanisms of antibiotic resistance. <em>Galleria mellonella</em> infection models were used to investigate the changes in virulence.</div></div><div><h3>Results</h3><div>The study described the changes of three strains of ST11-K64 carbapenem-resistant <em>K. pneumoniae</em> associated with pulmonary infection in vivo. The transition from a ceftazidime-avibactam-susceptible but imipenem-resistant isolate (JXZRKP1) to a ceftazidime-avibactam-resistant but imipenem-susceptible isolate (JXZRKP2) was attributed to the transformation of the <em>bla</em>_KPC gene from <em>bla</em>_KPC-2 to <em>bla</em>_KPC-71 and upregulation of <em>bla</em>_KPC gene expression. Notably, the <em>bla</em>_KPC-71 enzyme exhibited a Ser182 duplication compared to the wild-type <em>bla</em>_KPC-2 carbapenemase. The <em>bla</em>_KPC gene of three strains was carried by the IS<em>26</em>-mediated tandem core structure IS<em>Kpn27</em>-<em>bla</em>_KPC-IS<em>1182</em> on an IncFII-type plasmid. Furthermore, in comparison with JXZRKP2, the virulence plasmid of JXZRKP3 lost the aerobactin-encoding genes (<em>iucABCD-iutA</em>), resulting in diminished virulence in <em>G. mellonella</em> infection models, but there was no significant difference(<em>P</em> &gt; .05).</div></div><div><h3>Conclusions</h3><div>We first discovered that the mutation from <em>bla</em>_KPC-2 to <em>bla</em>_KPC-71 leads to resistance to ceftazidime-avibactam, followed by the loss of the aerobactin-encoding gene (<em>iucABCD-iutA</em>) on the virulence plasmid in vivo. This study underscores the complexity of addressing carbapenem-resistant <em>K. pneumoniae</em> infections.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 166-170"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The resistance trends in Mycobacterium kansasii pulmonary isolates and identification of risk factors for drug resistance in Taiwan","authors":"Sheng-Bin Fan ,&nbsp;Hung-Ling Huang ,&nbsp;Hung-Pin Tu ,&nbsp;Benjamin Sobkowiak ,&nbsp;Meng-Hsuan Cheng ,&nbsp;Wei-Chang Huang ,&nbsp;Yi-Wen Huang ,&nbsp;Shang-Yi Lin ,&nbsp;Inn-Wen Chong ,&nbsp;Po-Liang Lu","doi":"10.1016/j.jgar.2025.11.001","DOIUrl":"10.1016/j.jgar.2025.11.001","url":null,"abstract":"<div><h3>Objectives</h3><div><em>Mycobacterium kansasii</em> (<em>M. kansasii</em>) pulmonary disease is an emerging global health concern, and the pathogen's resistance to antimicrobial agents is challenging. Understanding the epidemiology of drug resistance rates and the associated risk factors is useful for guiding antimicrobial agent selection for <em>M. kansasii</em> treatment.</div></div><div><h3>Methods</h3><div>This retrospective cohort study analysed 361 pathogenic <em>M. kansasii</em> isolates collected from patients with <em>M. kansasii</em> pulmonary disease in two tertiary medical centres in Taiwan between 2011 and 2022. Antimicrobial susceptibility testing was performed using Sensititre™ SLOMYCO1 or SLOMYCO2, and MIC breakpoints were according to CLSI 2018. We applied multivariate logistic regression and Cochran–Mantel–Haenszel test to assess the factors associated with drug resistance.</div></div><div><h3>Results</h3><div>Most <em>M. kansasii</em> isolates in Taiwan remained susceptible to the first-line agents, including rifampin (92.2%) and clarithromycin (98.6%). High resistance rates were observed in ciprofloxacin (42.7%), doxycycline (56.2%), and trimethoprim/sulfamethoxazole (87.8%). The drug resistance rates of tested antibiotics for <em>M. kansasii</em> increased notably in 2018–2022 compared to those between 2015–2017. <em>M. kansasii</em> isolates from central Taiwan exhibited significantly higher resistance rates in all drugs compared to those in southern Taiwan. Pulmonary fibrocavitary lesion was an independent risk factor for resistance to rifampin and ciprofloxacin.</div></div><div><h3>Conclusions</h3><div>The study reveals increasing resistance to the first- and second-line agents in <em>M. kansasii</em> isolates across Taiwan. Resistance epidemiology differed between regions. Fibrocavitary lung lesion was significantly associated with drug resistance. These findings underscore the importance of region-specific surveillance to undergo individualized treatment strategies for <em>M. kansasii</em> pulmonary disease.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 49-56"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multicentric evaluation of the MTS™ Synergy Application System for reliable antibiotic synergy testing in clinical laboratories","authors":"Edoardo Carretto ,&nbsp;Stefano Andreoni ,&nbsp;Richard Aschbacher ,&nbsp;Daniela Barbarini ,&nbsp;Simone Bramati ,&nbsp;Flavia Brovarone ,&nbsp;Claudio Farina ,&nbsp;Angela Papa ,&nbsp;Andrea Rocchetti ,&nbsp;Giuseppe Russello ,&nbsp;Vittorio Sambri ,&nbsp;Assunta Sartor ,&nbsp;Paolo Gaibani","doi":"10.1016/j.jgar.2025.12.010","DOIUrl":"10.1016/j.jgar.2025.12.010","url":null,"abstract":"<div><h3>Objectives</h3><div>The rise of antimicrobial resistance poses a major challenge for both clinicians and clinical microbiologists. There is an increasing need for user-friendly and reliable methods to assess the activity of antibiotics against multidrug-resistant (MDR) strains. Although synergy testing provides valuable insights, conventional methods such as checkerboard assays and time-kill studies are labour-intensive, technically demanding, and difficult to standardize. This study evaluated the MTS™ SAS (MIC Test Strip – Synergy Application System, Liofilchem, Italy), a commercial gradient diffusion assay developed for antibiotic synergy testing.</div></div><div><h3>Methods</h3><div>The performance of MTS™ SAS was evaluated in comparison with the checkerboard microdilution method, used as the reference standard. Nine antibiotic combinations were tested against ten different bacterial strains across 11 Italian hospitals. Inter-laboratory reproducibility and agreement with the reference method were analysed.</div></div><div><h3>Results</h3><div>The concordance between MIC test strips and the broth microdilution (BMD) method was 98.4%, with 1.6% showing discordant results – all within a 3-dilution range. Among 996 synergy determinations, MTS™ SAS demonstrated high reproducibility across all centers (96.7%), while only 3.3% of tests showed discordant synergy classifications (e.g., synergy vs. indifference). Comparison with the checkerboard method demonstrated an overall concordance of 96.2%, despite the absence of specific operator training at each site.</div></div><div><h3>Conclusion</h3><div>These findings support MTS™ SAS as a practical and reliable alternative to conventional synergy testing methods, particularly suitable for routine clinical settings and laboratories lacking advanced microbiological expertise.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 209-213"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation and in vitro evaluation of bacteriophages against Pseudomonas aeruginosa isolated from burn wounds of human patients and hospital environment","authors":"Rabia Kanwar ,&nbsp;Muhammad Aamir Aslam ,&nbsp;Sajjad Ur Rahman ,&nbsp;Muhammad Saqib","doi":"10.1016/j.jgar.2025.10.012","DOIUrl":"10.1016/j.jgar.2025.10.012","url":null,"abstract":"<div><h3>Objective</h3><div>Multidrug resistance <em>Pseudomonas aeruginosa</em> is a global public health issue, and bacteriophages are an effective alternative therapy over antibiotics to combat antibiotic resistance. This study was designed to isolate bacteriophages and determine their antimicrobial potential against <em>P. aeruginosa</em> isolated from burn wounds and the environment of the burn ward.</div></div><div><h3>Methods</h3><div>A total of 100 random swab samples were collected from the burn ward, including 50 from the burn wounds and 50 from the environment and proceeded for further investigations at the University of Agriculture Faisalabad. <em>P. aeruginosa</em> was confirmed by genomic detection of <em>OprL</em> gene. Bacteriophages were isolated from sewage water through the agar overlay method, and their lytic spectrum was determined. Genome sequencing and analysis was performed. Phage stability and synergism between phage and antibiotics were analysed.</div></div><div><h3>Results</h3><div>Overall, 50 samples were positive for <em>P. aeruginosa</em>, in which 35 of 50 were positive from wounds of patients with burns, and 15 of 50 were positive from the hospital environment. <em>OprL</em>-positive strains were selected for bacteriophage isolation. Two phages, PhPa-6 and PhPa-4, with lytic spectra of 88 % and 60 %, respectively, were selected. The genome sizes of PhPa-6 and PhPa-4 were 186.978 kb and 73.3 kb, respectively. A cocktail of these phages has shown an active in vitro synergistic effect with ciprofloxacin (0.125 µg/mL).</div></div><div><h3>Conclusions</h3><div>A cocktail of PhPa-6 and PhPa-4 in combination with ciprofloxacin displayed significant lytic activity under in vitro conditions and a broad host range against <em>P. aeruginosa</em> isolates from patients with burns.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 22-30"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145431105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"in vitro antibacterial activity of nordihydroguaiaretic acid combined with ceftriaxone against carbapenem-resistant Klebsiella pneumoniae","authors":"Chengjiao Luo ,&nbsp;Hua Tan ,&nbsp;Hang Sun ,&nbsp;Xianwei Zhang ,&nbsp;Qian Chen","doi":"10.1016/j.jgar.2025.10.007","DOIUrl":"10.1016/j.jgar.2025.10.007","url":null,"abstract":"<div><h3>Objective</h3><div>This study investigated the interplay between biofilm formation and efflux pumps in carbapenem-resistant <em>Klebsiella pneumoniae</em> (CRKP) and evaluated the biofilm inhibition by nordihydroguaiaretic acid (NDGA) along with the efficacy of its combination with ceftriaxone (CRO) against CRKP, to inform the development of novel therapeutic strategies against multidrug-resistant infections.</div></div><div><h3>Methods</h3><div>Efflux pump genes were detected via PCR. Biofilm formation was quantified by crystal violet staining and categorized by the biofilm formation index (BFI) classification. Strong biofilm producers (BFI &gt; 4 × negative control) were selected for <em>in vitro</em> models. Efflux pump gene expression was compared between biofilm and planktonic states using qRT-PCR. NDGA’s biofilm inhibition and NDGA-CRO synergy were assessed via checkerboard assays.</div></div><div><h3>Results</h3><div>Among the 86 CRKP isolates, 51.16% (44/86) were classified as strong biofilm producers, followed by moderate (17.44%, 15/86), weak (20.93%, 18/86), and negative (10.47%, 9/86) producers. Efflux pump genes (<em>acrA, acrB, tolC, oqxA, oqxB</em>) were detected in 100%, 100%, 100%, 97.7%, and 98.84% of isolates. Gene expression was significantly upregulated in biofilm versus planktonic state (<em>P</em> &lt; 0.05). NDGA (≥16 µg/mL) inhibited biofilm formation, and its combination with CRO exhibited additive (63.64%) and synergistic (36.36%) effects.</div></div><div><h3>Conclusion</h3><div>Efflux pumps and biofilms synergistically enhance CRKP resistance. By inhibiting both efflux-mediated antibiotic extrusion and biofilm formation, NDGA resensitizes CRKP to CRO. This <em>in vitro</em> efficacy supports further development, pending <em>in vivo</em> safety studies in animal models.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 31-37"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145401086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First identification of a multidrug-resistant Pseudomonas kurunegalensis clinical isolate co-carrying blaAFM-1 and blaIMP-1 in China","authors":"Shuwei Fan ,&nbsp;Yuzhuo Gong ,&nbsp;Chunxiao Chen ,&nbsp;Jingchao Shi ,&nbsp;Cong Wu","doi":"10.1016/j.jgar.2025.12.007","DOIUrl":"10.1016/j.jgar.2025.12.007","url":null,"abstract":"<div><h3>Objectives</h3><div>The objective of this study was to elucidate the genetic context and characterize chromosome co-carrying <em>bla</em>_AFM-1 and <em>bla</em>_IMP-1 in a multidrug-resistant <em>Pseudomonas kurunegalensis</em> (<em>P. kurunegalensis</em>) isolate obtained from human urine using whole-genome sequencing.</div></div><div><h3>Methods</h3><div>This <em>P. kurunegalensis</em> isolate JC172 co-harbouring <em>bla</em>_AFM-1 and <em>bla</em>_IMP-1 underwent a comprehensive investigation that included antimicrobial susceptibility testing, conjugation assays, whole-genome sequencing and bioinformatic analyses. To depict the evolutionary dynamics of <em>P. kurunegalensis</em> strains on a global scale, a phylogenetic tree was generated based on single nucleotide polymorphisms of core genomes.</div></div><div><h3>Results</h3><div>JC172 was classified as <em>P. kurunegalensis</em> based on sequencing results and average nucleotide identity (ANI) assessments. This isolate was designated as ST114 and possesses a chromosome with 5 855 340 base pairs, exhibiting a GC content of 61.9%. Several resistance genes, including <em>bla</em>_AFM-1 and <em>bla</em>_IMP-1, <em>bla</em>_OXA-246 and <em>tmexC3D2-toprJ1</em> were identified on the chromosome. Genomic analysis revealed that <em>bla</em>_AFM-1 was situated within a core module of the <em>TnAs3</em>-<em>bla</em>_AFM-1 unit, which is bordered by class 1 integrons. This arrangement implies a significant potential for <em>bla</em>_AFM-1 dissemination.</div></div><div><h3>Conclusions</h3><div>Our study revealed that <em>bla</em>_AFM-1 and <em>bla</em>_IMP-1, <em>bla</em>_OXA-246 and <em>tmexC3D2-toprJ1</em> were harboured by <em>P. kurunegalensis</em>. We suggested that ST114 <em>P. kurunegalensis</em> may serve as a reservoir for resistance genes.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 162-165"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of zoonotic Coxiella burnetii causing chronic Q fever endocarditis in a Chinese geriatric patient by mNGS","authors":"Hui Wang ,&nbsp;Jie Sheng ,&nbsp;Ying Zhang ,&nbsp;Hao Lan ,&nbsp;Xiaofeng Lu ,&nbsp;Xi Li ,&nbsp;Xiaofei Zhao","doi":"10.1016/j.jgar.2025.09.015","DOIUrl":"10.1016/j.jgar.2025.09.015","url":null,"abstract":"<div><h3>Objective</h3><div>Q (query) fever, caused by <em>Coxiella burnetii</em>, is often linked to negative bacterial cultures, with infective endocarditis with negative cultures difficult to diagnose and treat. Our case demonstrates that metagenomic next-generation sequencing (mNGS) is able to provide a rapid and accurate method for pathogenetic diagnosis in infectious diseases.</div></div><div><h3>Case presentation</h3><div>A case of infective endocarditis with negative blood cultures is reported in a male patient with a history of sheep farming and previous aortic valve replacement and atrial septal defect atrial septal defect repair. Blood tests showed positive serum immunofluorescent antibodies to <em>Rickettsia</em>, while mNGS of perivalvular abscess tissue suggested <em>C. burnetii</em>. Doxycycline 0.1 g q12h and hydroxychloroquine 0.2 g q12h were used for postoperative antibiotic treatment. The genome of <em>C. burnetii</em> C2245173Z was assembled on the Illumina platform and no known antibiotic resistance genes were detected. Phylogenetic analysis of the <em>C. burnetii</em> genome showed a genetic relationship between animal- and human-derived strains.</div></div><div><h3>Conclusions</h3><div>mNGS could provide a rapid and accurate assay for clinical diagnosis and play a decisive role in the pathogenetic diagnosis of some infectious diseases. Doxycycline plus hydroxychloroquine remains an effective treatment for chronic Q fever endocarditis. In addition, phylogenetic tree analysis indicates that <em>C. burnetii</em> infection may pose a potential risk to humans working with livestock.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 192-195"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncommon pulmonary mycobacterium wolinskyi infection in a hemodialysis patient","authors":"Lin Zheng ,&nbsp;Yanwan Shangguan ,&nbsp;Wanru Guo ,&nbsp;Zhongkang Ji ,&nbsp;Kaijin Xu","doi":"10.1016/j.jgar.2025.09.006","DOIUrl":"10.1016/j.jgar.2025.09.006","url":null,"abstract":"<div><div>In recent years, the detection rate of nontuberculous mycobacteria has increased, drawing attention in clinical settings. Here, we present a case of pulmonary <em>Pseudomonas aeruginosa</em> and <em>Mycobacterium wolinskyi</em> coinfection in a 60-year-old hemodialysis recipient. To the best of our knowledge, this is the first instance of isolating the <em>M. wolinskyi</em> strain from human respiratory samples, including a comprehensive exploration of its susceptibility to clinically available antimicrobials. This discovery deepened our understanding of the infection spectrum of <em>M. wolinskyi</em>, highlighting the need to consider the potential for coinfections with common pathogens and less common atypical pathogens when managing immunocompromised patients. Furthermore, this study also assessed the in vitro antibacterial activity of newly available antibacterial drugs in clinical practice against the <em>M. wolinskyi</em> strain.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 134-137"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population pharmacokinetics of imipenem in solid tumor patients with infections: A real-world study","authors":"Tingting Xu ,&nbsp;Tingting Zou ,&nbsp;Junyan Zhang ,&nbsp;Zhuoran Li ,&nbsp;Fangyu Li ,&nbsp;Juan Du ,&nbsp;Zhiying Hao","doi":"10.1016/j.jgar.2025.09.005","DOIUrl":"10.1016/j.jgar.2025.09.005","url":null,"abstract":"<div><h3>Objectives</h3><div>To characterize the population pharmacokinetics (PPK) of imipenem in critically ill solid tumor patients and to optimize dosing regimens through pharmacodynamic analysis.</div></div><div><h3>Methods</h3><div>A PPK model was developed using nonlinear mixed-effects modeling (Monolix 2023R1) based on 25 critically ill solid tumor patients with infections. Model selection used objective function value (OFV), Akaike/Bayesian information criteria(AIC/BIC), and goodness-of-fit diagnostics. Covariate screening involved a dual-algorithm approach (SAMBA and COSSAC) for validation. Monte Carlo simulations (n=10,000) evaluated the probability of target attainment (PTA) for 100% fT&gt;MIC across different renal function groups.</div></div><div><h3>Results</h3><div>A linear one-compartment model best described imipenem pharmacokinetics. Typical population estimates were clearance (CL) = 2.7 L/h and volume of distribution (Vd) = 10.6L—significantly lower than values reported in general critical care populations. Creatinine clearance (CLCR) and septic shock were identified as significant covariates affecting CL. Severe malnutrition contributed to reduced Vd. Simulations revealed: For MIC ≤2 mg·L⁻¹, 500 mg q6h achieved PTA &gt;90% when CLCR &gt;30 mL/min; for MIC = 4 mg·L⁻¹, 1000 mg q6h was required for patients with CLCR &gt;60 mL/min (PTA = 94.9–100%); no regimen achieved PTA &gt;20% for MIC ≥16 mg·L⁻¹.</div></div><div><h3>Conclusion</h3><div>This study highlights the significant effect of specific pathophysiological changes in solid tumor patients (such as cachexia-induced reduction in volume of distribution) on drug disposition, providing essential evidence for informing personalized imipenem dosing in this vulnerable group to improve efficacy and reduce resistance risks.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 107-114"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"blaNDM-5 is the predominant variant of blaNDM gene in Klebsiella species detected in Mississippi, USA","authors":"Srimadhav Nallani ,&nbsp;Saihou Ceesay ,&nbsp;Abiye Iyo,&nbsp;Lucersia Nichols,&nbsp;Daphne Ware,&nbsp;Beata Karolewicz","doi":"10.1016/j.jgar.2025.10.014","DOIUrl":"10.1016/j.jgar.2025.10.014","url":null,"abstract":"<div><h3>Objectives</h3><div>The Mississippi Public Health Laboratory conducts active surveillance of carbapenem-resistant <em>Enterobacterales</em> (CRE) infections as part of the Antimicrobial Resistance Laboratory Network (ARLN) program implemented by the United States Centers for Disease Control and Prevention (CDC). Here, we describe the prevalence of New Delhi Metallo-β-lactamase (<em>bla</em>_NDM) genes in <em>Klebsiella</em>, a major pathogen of the <em>Enterobacterales</em> order linked to nosocomial infections, between January 2022 and June 2025.</div></div><div><h3>Methods</h3><div>Carbapenemase activity was confirmed using the Modified Carbapenem Inactivation Method (mCIM). PCR was then performed on carbapenemase-positive isolates to detect <em>bla</em>_NDM genes. Whole-genome sequencing (WGS) was performed on 35 <em>bla</em>_NDM-positive isolates to identify <em>bla</em>_NDM gene variants, other antimicrobial resistance (AMR) determinants, virulence factors, and plasmids. Antibiotic susceptibility testing (AST) was determined by the Kirby-Bauer disk diffusion assay.</div></div><div><h3>Results</h3><div>Among the 35 NDM-positive <em>Klebsiella</em> species, the <em>bla</em>_NDM-5 variant was identified in 23 (65.7%) isolates, followed by <em>bla</em>_NDM-1 and <em>bla</em>_NDM-7 genes which were identified in 6/35 (17%) and 6/35 (17%) cases, respectively. A significant proportion of <em>bla</em>_NDM-5 cases also harbored additional β-lactamase genes such as <em>bla</em>_SHV family (18/23; 78%) and <em>bla</em>_TEM-1 (9/23; 39%) indicating multi-drug resistance. All 23 <em>bla</em>_NDM-5-positive isolates were resistant to carbapenems and broad-spectrum cephalosporins, but 13/23 (56.5%) remained susceptible to aztreonam. PlasmidFinder analysis identified IncX3 (20/23) and IncFIB(K) (19/23) as the predominant plasmid replicons among these isolates.</div></div><div><h3>Conclusion</h3><div>The emergence and spread of bacteria carrying <em>bla</em>_NDM-5 gene poses a significant threat to public health in Mississippi. Our dataset warrants further study to investigate the potential role of plasmids in <em>bla</em>_NDM-5 dissemination.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 282-286"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}