International Journal of Antimicrobial Agents最新文献

{"title":"Unveiling the clonal dynamics and transmission mechanism of carbapenem-resistant klebsiella pneumoniae in the ICU environment","authors":"Xinhong Han ,&nbsp;Meijun Song ,&nbsp;Qing Yu ,&nbsp;Junxin Zhou ,&nbsp;Huangdu Hu ,&nbsp;Yan Jiang ,&nbsp;Qiucheng Shi ,&nbsp;Yongyi Chen ,&nbsp;Qing Yang ,&nbsp;Xiaoxing Du ,&nbsp;Caiping Mao ,&nbsp;Yunsong Yu","doi":"10.1016/j.ijantimicag.2025.107532","DOIUrl":"10.1016/j.ijantimicag.2025.107532","url":null,"abstract":"<div><div>CRKP infections are a significant public health threat due to their high mortality and limited treatment options. This study aimed to investigate CRKP colonization and clonal dissemination mechanism in an ICU. From August 2019 to December 2019, 8668 samples were collected from patients and the ICU environment for CRKP screening. Positive samples underwent antimicrobial susceptibility testing, whole-genome sequencing, and molecular epidemiological analysis. Disinfectant sensitivity and ultraviolet (UV) resistance experiments were conducted to evaluate clonal persistence. The overall CRKP positive rate was 4.85% (420/8668), with higher rates in patients (14.77%, 247/1672) compared to environmental surfaces (2.47%, 173/6996). Intestinal and ventilator-related surfaces were identified as high-risk colonization sites. Molecular analysis revealed six sequence types, with ST11-KL64 (44.05%, 185/420) and ST15-KL112 (24.05%, 101/420) as dominant clones, both exhibiting elevated virulence. Notably, the emerging ST15-KL112 clone demonstrated enhanced resistance to disinfectants including chlorhexidine (MIC 8 mg/L) and benzalkonium chloride (32 mg/L). While most isolates produced KPC-2 (72.86%), OXA-232 prevalence (25.23%) exceeded prior reports. Crucially, ST11 strains survived standard UV disinfection (60-second exposure) at rates 1.3- to 5-fold higher than other clones (p &lt; 0.01). Our findings highlight the critical role of disinfectant resistance in sustaining CRKP transmission. To mitigate outbreaks, we advocate for disinfectant rotation protocols targeting disinfectant-resistant clones and prolonged UV exposure times in ICUs. The persistence of resistant CRKP clones in the ICU environment, particularly their high tolerance to disinfectants, highlights the urgent need for enhanced infection control strategies, including tailored disinfection protocols and surveillance programs.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 3","pages":"Article 107532"},"PeriodicalIF":4.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015030","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":"Genetic framework and evolutionary dynamics of mcr-positive Klebsiella pneumoniae from 2000 to 2023","authors":"Xi-Wei Zhang ,&nbsp;Xi-Yi Huang ,&nbsp;Zhuo-Yang Zhou ,&nbsp;Bo-Lin Li ,&nbsp;Jie-Hong Lu ,&nbsp;Jing-Jie Song ,&nbsp;Xiao-Yan Li","doi":"10.1016/j.ijantimicag.2025.107533","DOIUrl":"10.1016/j.ijantimicag.2025.107533","url":null,"abstract":"<div><h3>Objective</h3><div>The international transmission of the colistin resistance gene <em>mcr</em> in Enterobacteriaceae poses significant public health burdens, while the understanding of the population structure and evolutionary history of <em>mcr</em>-positive <em>Klebsiella pneumoniae</em> worldwide remains unclear.</div></div><div><h3>Methods</h3><div>Here, we conducted a genomic analysis on 463 sequences of <em>K. pneumoniae</em> harbouring <em>mcr</em> genes from public database between 2000 and 2023.</div></div><div><h3>Results</h3><div>A total of 6 <em>mcr</em> variants (<em>mcr-1</em>, -<em>2</em>, -<em>3</em> and -<em>8</em> to -<em>10</em>) were detected, with <em>mcr</em>-<em>9</em> (36.1%), <em>mcr</em>-<em>1</em> (33.7%) and <em>mcr</em>-<em>8</em> (29.2%) genes being the most common. Of total isolates, 43.4% (201/463) carried carbapenemase genes (<em>bla</em>_NDM, <em>bla</em>_KPC, <em>bla</em>_IMP, <em>bla</em>_{OXA-48/181/232}, <em>bla</em>_VIM and <em>bla</em>_GES) and 15.3% of isolates (71/463) contained hypervirulent genes (<em>iucA</em> or <em>iroB</em>). Correlation analysis indicated <em>mcr</em>-<em>1</em>/<em>8</em>/<em>9</em> genes were positively correlated with specific genomic elements that were rarely described, including <em>mcr</em>-<em>1</em> with <em>iucABC</em> and <em>iutA; mcr</em>-<em>8</em> with <em>oqxB; mcr-9</em> with <em>dfrA19</em>; and IS<em>Esa</em> and repA (R absolute value &gt; 0.3; <em>p</em> &lt; 0.01). The population of <em>K. pneumoniae</em> can be classified into 6 clusters, some isolates co-harbouring <em>mcr</em> and carbapenemase genes exhibited high level of genetic similarity and dispersed in several countries, indicating the possibility of clonal transmission. <em>mcr</em>-<em>9</em> gene was introduced into <em>K. pneumoniae</em> in 1978 before the time of <em>mcr</em>-<em>1</em> gene in 1988 and <em>mcr</em>-<em>8</em> gene in 1993. We found <em>mcr</em>-<em>1</em>/<em>8</em>/<em>9</em> genes in <em>K. pneumoniae</em> evolved high-risk lineages in specific geographical location (China, Thailand and the United Kingdom) that most isolates typically contained <em>iucA, bla</em>_NDM or <em>bla</em>_KPC.</div></div><div><h3>Conclusions</h3><div>This study highlighted that continuous surveillance for the evolution of <em>mcr</em>-positive <em>K. pneumoniae</em> harbouring <em>iucA</em> or carbapenemase genes is essential.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 3","pages":"Article 107533"},"PeriodicalIF":4.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965747","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(25)00086-X","DOIUrl":"10.1016/S0924-8579(25)00086-X","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 1","pages":"Article 107529"},"PeriodicalIF":4.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905845","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":"Effects of different resistance mechanisms on bacterial response to meropenem, ciprofloxacin, and their combination described by next-generation mechanism-based modelling","authors":"Alice E. Terrill ,&nbsp;Jessica R. Tait ,&nbsp;Kate E. Rogers ,&nbsp;Wee L. Lee ,&nbsp;Carla López-Causapé ,&nbsp;Xiaoyu Wang ,&nbsp;Jiangning Song ,&nbsp;Roger L. Nation ,&nbsp;Antonio Oliver ,&nbsp;Cornelia B. Landersdorfer","doi":"10.1016/j.ijantimicag.2025.107528","DOIUrl":"10.1016/j.ijantimicag.2025.107528","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the effects of different bacterial resistance mechanisms on the response of isogenic strains of <em>Pseudomonas aeruginosa</em> to meropenem and ciprofloxacin, in monotherapy and combination.</div></div><div><h3>Methods</h3><div>Seven isogenic <em>P. aeruginosa</em> strains were used: the PAO1 wild-type reference parent strain, PAΔAD (AmpC overexpression), PAOD1 (OprD porin loss), PAΔmexR (MexAB-OprM overexpression), and strains with two of these mutations (PAΔDMxR, PAOD1MxR, PAOD1ΔD). Each strain was exposed to constant meropenem and/or ciprofloxacin concentrations over 72 h. Pharmacokinetic/pharmacodynamic indices, i.e. the percentage of time the free meropenem concentration exceeded the MIC of the pathogen (%<em>f</em>T_˃MIC) and the ratio of the area under the free ciprofloxacin concentration-time curve over 24 h to MIC (<em>f</em>AUC/MIC), were calculated. A novel mechanism-based mathematical model was developed to describe the bacterial count profiles over time.</div></div><div><h3>Results</h3><div>The antibiotic exposures in monotherapy required to suppress regrowth varied between isogenic strains, even when strains had the same MIC; highlighting limitations of relying solely on MIC to inform dosing. Combination therapies, which cannot be predicted by pharmacokinetic/pharmacodynamic indices, were both synergistic and bactericidal at 72 h in five of the seven strains. All viable counts across all strains with monotherapies, combinations, and controls (<em>n</em> = 292 curves) were simultaneously modelled. The model accounted for different resistance mechanisms present across strains, while keeping all drug effect parameters the same between strains. The responses of strains with two resistance mutations were well described by the model developed from strains with a single mutation.</div></div><div><h3>Conclusions</h3><div>Overall, the mechanism-based mathematical model was predictive for &gt;96% of treatments.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 3","pages":"Article 107528"},"PeriodicalIF":4.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993142","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":"Antimicrobial suppressive therapy in prosthetic valve endocarditis rejected from surgery despite indication","authors":"Jérémie Tillement ,&nbsp;Nahema Issa ,&nbsp;Julien Ternacle ,&nbsp;Victor Hémar ,&nbsp;Antoine Beurton ,&nbsp;Olivier Busuttil ,&nbsp;Hélène Chaussade ,&nbsp;Marina Dijos ,&nbsp;Carine Greib ,&nbsp;Louis Labrousse ,&nbsp;Julien Peltan ,&nbsp;Olivia Peuchant ,&nbsp;Gaetane Wirth ,&nbsp;Claire Roubaud-Baudron ,&nbsp;Fabrice Camou ,&nbsp;Romain Boulestreau","doi":"10.1016/j.ijantimicag.2025.107526","DOIUrl":"10.1016/j.ijantimicag.2025.107526","url":null,"abstract":"<div><h3>Background</h3><div>Prosthetic valve endocarditis (PVE) incidence is rising in older patients, often rejected for surgery, leading them to a poor prognosis. Optimal antibiotic management is unknown for these patients. We compared the efficacy and safety of suppressive (SAT) versus conventional antimicrobial therapy (CAT) in this setting.</div></div><div><h3>Methods</h3><div>We conducted a prospective, multicentric, cohort study in southwest France including patients with PVE rejected from surgery despite indication, and surviving the initial 6 weeks of intravenous therapy. Beyond this period, patients could or not receive SAT, according to endocarditis team decision. Primary outcome was a composite endpoint of one-year all-cause mortality and PVE-related hospitalization. Secondary outcome was the incidence and nature of SAT-related adverse events.</div></div><div><h3>Results</h3><div>Between 2012 and 2022, 88 patients were included in the study, 42 receiving SAT and 46 CAT. Mean age was 69.4 ± 16.4 years and patients were highly comorbid (mean Charlson Comorbidity Index 5.6 ± 2.7). Main organisms included <em>Streptococcus</em> spp. (26/88, 29.5%) and <em>Staphylococcus aureus</em> (25/88, 28.4%). The primary composite outcome occurred in 7/42 (16.7%) patients in the SAT group, and 16/46 (34.8%) in the CAT group. Using a Cox model, SAT was significantly and independently associated with a lower incidence of one-year primary outcome (Hazard ratio 0.23, 95% CI 0.08–0.67, <em>P = 0.</em>007). Adverse effects in the SAT group were reported for 6/42 patients (14.3%). These effects were limited, causing only one treatment discontinuation.</div></div><div><h3>Conclusion</h3><div>In patients with PVE rejected from surgery despite indication, SAT may be safe and associated with better outcomes than CAT.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 3","pages":"Article 107526"},"PeriodicalIF":4.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985285","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":"A review of recently discovered mechanisms of cephalosporin resistance in Pseudomonas aeruginosa","authors":"Madeleine T. Hardie Boys,&nbsp;Daniel Pletzer","doi":"10.1016/j.ijantimicag.2025.107527","DOIUrl":"10.1016/j.ijantimicag.2025.107527","url":null,"abstract":"<div><div><em>Pseudomonas aeruginosa</em> frequently causes respiratory tract infections in immunocompromised patients as well as bloodstream, urinary tract, skin, and soft tissue infections. The increasing prevalence of multidrug-resistant <em>P. aeruginosa</em> strains poses a significant clinical challenge. Cephalosporin antibiotics from the β-lactam class are commonly prescribed to treat infections owing to their broad spectrum of activity and generally low host toxicity. <em>P. aeruginosa</em> utilizes β-lactamase enzymes, efflux pumps, and mutations in outer membrane porins/transporters and target proteins, all of which confer resistance to cephalosporin antibiotics.</div><div>This review categorizes resistance mechanisms into (i) well-characterized pathways, such as AmpC β-lactamase and Mex efflux pumps, (ii) recently described mutations linked to cephalosporin resistance (e.g., <em>ygfB, sltB1, pbp3, galU, pmrAB, fusA1</em>, and <em>gyrA</em>), and (iii) hypothetical β-lactamases and other mechanisms requiring further validation.</div><div>A variety of β-lactamase inhibitors have been developed to overcome β-lactamase-mediated resistance, but resistance has already been observed toward inhibitors via the accumulation of mutations within the targeted β-lactamase enzyme or increased activity of efflux pumps.</div><div>Understanding the regulation and pathways that lead to resistance is crucial in developing effective strategies to combat <em>P. aeruginosa</em> infections and extending the therapeutic lifespan of cephalosporin antibiotics.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107527"},"PeriodicalIF":4.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009501","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":"International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page","authors":"","doi":"10.1016/j.ijantimicag.2025.107525","DOIUrl":"10.1016/j.ijantimicag.2025.107525","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 1","pages":"Article 107525"},"PeriodicalIF":4.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877438","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":"Association of antibiotics with Stevens–Johnson syndrome and toxic epidermal necrolysis: A real-world pharmacovigilance study","authors":"Xin Yan ,&nbsp;Junlong Ma ,&nbsp;Chengxian Guo ,&nbsp;Guoping Yang","doi":"10.1016/j.ijantimicag.2025.107524","DOIUrl":"10.1016/j.ijantimicag.2025.107524","url":null,"abstract":"<div><h3>Background</h3><div>Recent reports suggest antibiotics may cause severe allergic reactions, such as Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), exacerbating concerns about antibiotic safety.</div></div><div><h3>Objective</h3><div>Given the limited real-world evidence, this study aims to analyse the FDA Adverse Event Reporting System to investigate the association between various antibiotics and SJS/TEN risk.</div></div><div><h3>Methods</h3><div>Reports from infected patients (Q1 2014–Q4 2023) were extracted from the FDA Adverse Event Reporting System. Disproportionality analysis using information component identified risk signals of antibiotics associated with SJS/TEN. Subgroup analyses investigated the impact of age and gender on antibiotic-associated SJS/TEN. Also, a time of onset analysis was performed.</div></div><div><h3>Results</h3><div>Among 78 593 infected patients, 1221 cases of SJS/TEN were identified from 30 369 antibiotic administrations. The median age of patients with SJS was 63 y, and with TEN was 60 y. Eleven positive signal drugs were detected through disproportionality analysis. Amoxicillin, piperacillin, ceftriaxone, cefuroxime, cefotaxime, azithromycin, sulfamethoxazole, trimethoprim, vancomycin, doxycycline, and gentamicin exhibited significant risk associations with SJS/TEN. Sulfamethoxazole had the highest risk. Patients with pneumonia, urinary tract infections, and sepsis had higher risks than those with respiratory tract infections. Male patients using specific antibiotics may have a higher risk than females, with no significant age difference.</div></div><div><h3>Conclusions</h3><div>Antibiotics including penicillins, cephalosporins, azithromycin, sulfamethoxazole, trimethoprim, vancomycin, doxycycline, and gentamicin are associated with an increased risk of SJS/TEN, with sulfamethoxazole presenting the highest risk. Patients with pneumonia, urinary tract infections, and sepsis are particularly vulnerable. These findings highlight the need for personalized antibiotic regimens based on infection site and patient gender.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107524"},"PeriodicalIF":4.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947694","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":"High-level ceftazidime-avibactam resistance by in-host evolution of blaKPC genes: Emergence of a novel blaKPC-102 variant and increase of blaKPC-33 copy number in Klebsiella pneumoniae strains from a lung transplantation recipient","authors":"Yulin Zhang ,&nbsp;Ziyao Li ,&nbsp;Huihui Shi ,&nbsp;Zichen Lei ,&nbsp;Dongya Pu ,&nbsp;Qi Liu ,&nbsp;Feilong Zhang ,&nbsp;Jiankang Zhao ,&nbsp;Xinmeng Liu ,&nbsp;Binghuai Lu ,&nbsp;Bin Cao","doi":"10.1016/j.ijantimicag.2025.107521","DOIUrl":"10.1016/j.ijantimicag.2025.107521","url":null,"abstract":"<div><h3>Objective</h3><div>KPC-producing <em>Klebsiella pneumoniae</em> (Kp) infections have become one of the major threats to public health in China. Recently, the emergence of ceftazidime-avibactam (CZA) resistance due to the <em>bla</em>_KPC mutations has been increasingly reported.</div></div><div><h3>Methods</h3><div>Two CZA-susceptible Kp strains (Kp36854 carrying <em>bla</em>_KPC-2 and Kp37523 without <em>bla</em>_KPC) and two CZA-resistant Kp strains (Kp38935 carrying double copies of <em>bla</em>_KPC-33 and Kp38097 carrying a newly identified <em>bla</em>_KPC-102 gene) were isolated from a lung-transplanted patient during CZA treatment. This study analyzed the within-host evolutionary dynamics of <em>bla</em>_KPC in KPC-Kp strains.</div></div><div><h3>Results</h3><div>Compared with KPC-2, KPC-33 possessed only a D179Y substitution while KPC-102 harbored both D179Y and Y241D substitutions. We constructed KPC-δ33 with only a Y241D substitution, which means the correction of the first mutation that is also present in KPC-33 (D179Y). Cloning and expression experiments showed that CZA-MIC value of <em>E. coli</em> DH5α/pKPC102 was 512 mg/L, while CZA-MIC values of both <em>E. coli</em> DH5α/pKPC-33 and <em>E. coli</em> DH5α/pKPC-δ33 were 32/4 mg/L. Enzymatic kinetic analysis revealed that KPC-2 demonstrated the highest catalytic efficiency to nitrocefin and meropenem, whereas KPC-33 displayed higher catalytic efficiency against ceftazidime compared to other tested KPC variants. Regarding avibactam, KPC-2 showed the highest sensitivity, while KPC-δ33 and KPC-102 were less sensitive.</div></div><div><h3>Conclusion</h3><div>High-level CZA resistance was mediated by the novel <em>bla</em>_KPC-102 and double copies of <em>bla</em>_KPC-33 gene, respectively, in two porin-deficient Kp strains from one patient. The CZA resistance resulting from <em>bla</em>_KPC mutation could be selected and evolved to be more diverse and heterogeneous within the host after CZA therapy. It is very essential to perform the surveillance of CZA-resistance for clinicians during treatment.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107521"},"PeriodicalIF":4.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935608","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":"Synergistic activity of menadione in combination with colistin against colistin-susceptible and colistin-resistant Gram-negative bacteria","authors":"Jun Yang ,&nbsp;Huiying Yue ,&nbsp;Weifeng Wang ,&nbsp;Caiying Lin ,&nbsp;Chenchen Li ,&nbsp;Jiakuo Chen ,&nbsp;Jian-Hua Liu ,&nbsp;Yi-Yun Liu","doi":"10.1016/j.ijantimicag.2025.107523","DOIUrl":"10.1016/j.ijantimicag.2025.107523","url":null,"abstract":"<div><h3>Objective</h3><div>Antibiotic resistance poses a formidable challenge, especially with the emergence of multidrug-resistant Gram-negative bacteria. Colistin serves as a last-resort antibiotic to combat multidrug-resistance, but it is limited by its nephrotoxicity and rising resistance. This study introduces menadione, a synthetic form of vitamin K, as a potential adjuvant to enhance colistin's efficacy against both susceptible and resistant strains of Gram-negative bacteria.</div></div><div><h3>Methods</h3><div>Through checkerboard dilution assays, we demonstrate that menadione significantly lowers the MICs of colistin, with fractional inhibitory concentration indices ranging from 0.031 to 0.375. Furthermore, synergistic effects were confirmed via time–kill kinetics, indicating effective bacterial growth inhibition. The study also explores the mechanism underlying this synergy, revealing that menadione in combination with colistin disrupts the bacterial outer membrane, reduces the proton motive force and adenosine triphosphate content, and amplify the production of reactive oxygen species, contributing to bacterial cell death.</div></div><div><h3>Results</h3><div>Menadione was shown to prevent the evolution of colistin resistance.</div></div><div><h3>Conclusions</h3><div>This research highlights the potential of using menadione as a colistin adjuvant to combat antibiotic-resistant Gram-negative bacteria, providing a promising approach to extend the utility of existing antibiotics in clinical settings.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107523"},"PeriodicalIF":4.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015028","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}