International Journal of Antimicrobial Agents最新文献

{"title":"Comparison of ceftazidime-avibactam with other appropriate antimicrobial therapy for the treatment of OXA-48- or KPC-producing Enterobacterales infections in Türkiye: A multi-centre retrospective matched-cohort study","authors":"Abdullah Tarık Aslan ,&nbsp;Elif Seren Tanriverdi ,&nbsp;Sibel Yıldız Kaya ,&nbsp;Gozde Dalgan ,&nbsp;Neşe Saltoğlu ,&nbsp;Ezgi Yılmaz ,&nbsp;Yeliz Çiçek ,&nbsp;Mesut Yılmaz ,&nbsp;Çiğdem Erol ,&nbsp;Özlem Kurt Azap ,&nbsp;Gülşen Hazırolan ,&nbsp;Osman Dağ ,&nbsp;Zeynep Türe Yüce ,&nbsp;Pinar Sagiroglu ,&nbsp;Damla Boztaş ,&nbsp;Muhammed Cihan Işık ,&nbsp;Bariş Otlu ,&nbsp;Patrick N.A. Harris ,&nbsp;David L. Paterson ,&nbsp;Murat Akova","doi":"10.1016/j.ijantimicag.2025.107650","DOIUrl":"10.1016/j.ijantimicag.2025.107650","url":null,"abstract":"<div><h3>Objective</h3><div>Due to underrepresentation of carbapenemase-producing <em>Enterobacterales</em> infections in randomized controlled trials with ceftazidime-avibactam (CZA) and high cost of CZA therapy, other appropriate antimicrobial therapies (OAAT) are still being used for OXA-48- or KPC-producing <em>Enterobacterales</em> infections in Türkiye.</div></div><div><h3>Methods</h3><div>We conducted a multicentre retrospective 1:1 matched cohort study of patients who received ≥48 h of CZA or OAAT for documented OXA-48- or KPC-producing <em>Enterobacterales</em> infections. Patients were matched based on (1) the number of days (± 1 d) from the infection onset to the initiation of therapy, (2) INCREMENT-CPE score (± 1), (3) source of infection, (4) year of infectious episode, and (5) type of causative microorganism.</div></div><div><h3>Results</h3><div>From 5 Turkish university hospitals, 180 patients were enrolled. Baseline characteristics were all similar between treatment groups. At the time of treatment initiation, 63.9% of patients were in the intensive care unit, 35.6% had septic shock and 41.1% required mechanical ventilation support. Thirty-day mortality occurred in 35.6% (32/90) of patients treated with CZA and in 56.7% (51/90) of those receiving OAAT regimens (<em>P</em> = 0.004). Twenty-one-day clinical response was seen in 50% (45/90) and 26.7% (24/90) of patients receiving CZA and OAAT, respectively (<em>P</em> = 0.002). In multivariable logistic regression analyses, CZA treatment was associated with less likelihood of mortality (aOR = 0.37; 95% CI: 0.19–0.71; <em>P</em> = 0.003) and higher likelihood of 21-d clinical response (aOR = 3.32; 95% CI: 1.68–6.53; <em>P</em> &lt; 0·001).</div></div><div><h3>Conclusions</h3><div>Treatment with CZA is associated with more favourable clinical outcomes in treatment of OXA-48- or KPC-producing <em>Enterobacterales</em> infections. A randomized controlled trial is needed to confirm these results.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107650"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400641","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":"Impact of antimicrobial resistance measures and the emergence of COVID-19 on antimicrobial use throughout the Japanese population: A retrospective cohort study using a national claims database","authors":"Ryuji Koizumi ,&nbsp;Shinya Tsuzuki ,&nbsp;Yusuke Asai ,&nbsp;Kensuke Aoyagi ,&nbsp;Norio Ohmagari","doi":"10.1016/j.ijantimicag.2025.107667","DOIUrl":"10.1016/j.ijantimicag.2025.107667","url":null,"abstract":"<div><h3>Objective</h3><div>This study examined the impact of Japan’s National Action Plan on Antimicrobial Resistance (NAP) and the COVID-19 pandemic on national trends in antimicrobial consumption (AMC) for major infectious diseases.</div></div><div><h3>Methods</h3><div>This retrospective cohort study analysed claims data for the Japanese population from 2013 to 2020. AMC was expressed as defined daily doses per 1000 inhabitants per day. The target diseases included upper respiratory infection (URI), otitis media, pneumonia, diarrhoea, urinary tract infection, skin and soft tissue infection, and sexually transmitted infection. Seasonally adjusted interrupted time-series analyses were conducted to assess the impact of NAP publication in 2016 and the COVID-19 outbreak in 2020 on the numbers of medically attended cases and antimicrobial prescription rates.</div></div><div><h3>Results</h3><div>Total AMC declined from 2016 to 2019, and decreased further in 2020. There was a significant decrease in medically attended cases in 2020 when compared to the counterfactual scenario in which COVID-19 did not occur. AMC was positively correlated with the number of medically attended cases. Total antimicrobial prescription rates decreased after NAP publication and the COVID-19 outbreak. Among the diseases, prescription rates for URI, otitis media, and pneumonia significantly decreased after both events. However, the prescription rate for diarrhoea decreased after NAP publication but increased after COVID-19. No significant trends were detected for other diseases.</div></div><div><h3>Conclusions</h3><div>Antimicrobial prescriptions for respiratory infections steadily decreased after NAP publication, which may indicate the effects of antimicrobial stewardship activities. Continued monitoring is needed to clarify the long-term effects of the COVID-19 pandemic on antimicrobial use.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107667"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530588","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":"Consumption and expenditure on fidaxomicin and oral vancomycin for Clostridioides difficile infection: A 12-year longitudinal study of 43 countries and regions","authors":"Yin Zhang ,&nbsp;Xue Li ,&nbsp;Angel Y.S. Wong ,&nbsp;Vincent K.C. Yan ,&nbsp;Joseph E. Blais ,&nbsp;Jiaqi Wong ,&nbsp;Esther W. Chan ,&nbsp;Wai K. Leung","doi":"10.1016/j.ijantimicag.2025.107664","DOIUrl":"10.1016/j.ijantimicag.2025.107664","url":null,"abstract":"<div><h3>Background</h3><div>Current treatment guidelines recommend fidaxomicin and oral vancomycin as first-line treatments for <em>Clostridioides difficile</em> infection (CDI). Disparities in the prevalence of CDI and the availability of novel treatments necessitate understanding the contemporary trends in their consumption at the global level.</div></div><div><h3>Methods</h3><div>This longitudinal study used global pharmaceutical sales from IQVIA-MIDAS for fidaxomicin and oral vancomycin in 43 countries from 2012 to 2023. We measured defined daily doses per 100,000 inhabitants per year (DDD/100K) and manufacture-level prices, calculating changes using compound annual growth rates (CAGR). We conducted interrupted time-series analyses to assess the impact of guideline updates by Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America (IDSA/SHEA) on quarterly consumption.</div></div><div><h3>Results</h3><div>Overall fidaxomicin consumption increased from 21.68 DDD/100K in 2012 to 126.86 DDD/100K in 2023 (CAGR = 17.42%) and similar increases in expenditure (0.07–0.34 USD/capita; CAGR = 14.96%). Oral vancomycin consumption increased from 71.61 to 120.82 DDD/100K (CAGR = 4.87%), although with a decreasing trend in expenditure (0.20–0.03 USD/capita; CAGR = −15.16%). The earliest adoption of fidaxomicin in middle-income economies occurred five years later than in high-income economies. Despite higher CAGRs, consumption of fidaxomicin and oral vancomycin in middle-income economies was only 1.9% and 2.3%, respectively, of that in high-income economies in 2023. Following the IDSA/SHEA guideline updates, fidaxomicin consumption in Northern America increased immediately.</div></div><div><h3>Conclusion</h3><div>Consumption of fidaxomicin and oral vancomycin continues to increase globally; however, significant economic and geographical disparities in utilization highlight inequitable access to first-line CDI treatments.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107664"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471014","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":"NucS Thr74Ile confers mutator phenotype in a globally disseminated clinical Mycobacterium abscessus subsp. abscessus clone","authors":"Juan Li ,&nbsp;Junsheng Fan ,&nbsp;Zhili Tan ,&nbsp;Anqi Li ,&nbsp;Siyuan He ,&nbsp;Yani Lin ,&nbsp;Bing Li ,&nbsp;Haiqing Chu","doi":"10.1016/j.ijantimicag.2025.107677","DOIUrl":"10.1016/j.ijantimicag.2025.107677","url":null,"abstract":"<div><h3>Objective</h3><div>The emergence of mutations conferring resistance to first-line drugs, macrolides and amikacin, is a major cause of treatment failure in <em>Mycobacterium abscessus</em> complex (MABC) infections; however, mutator strains predisposed to developing drug-resistance mutations remain uncharacterized. NucS, a key DNA mismatch repair protein, maintains mycobacterial genomic stability. This study investigated whether naturally occurring NucS polymorphisms contribute to mutator phenotypes in clinical MABC strains.</div></div><div><h3>Methods</h3><div>The whole genome data of clinical MABC isolates obtained from public databases were analysed to identify naturally occurring NucS polymorphisms. Phylogenetic analysis was performed to elucidate the relationship between the common NucS Thr74Ile polymorphism and drug resistance mutations. The effects of polymorphisms on NucS activity were analysed by checking their impact on mutation rates of drug resistance using a <em>M. abscessus</em> subsp. <em>abscessus</em> (Mabs) homologous system.</div></div><div><h3>Results</h3><div>Seven NucS polymorphisms were identified. Notably, the Mabs (the most prevalent MABC subspecies) <em>nucS</em> C221T/<em>erm</em>(41) T28C isolates belong to a globally disseminated clone. These drug-sensitive strains exhibit heightened potential for acquired resistance to macrolides and amikacin conferred by <em>rrl</em> and <em>rrs</em> mutations, respectively, and some restore inducible macrolide-resistance by reverting to wild-type <em>erm</em>(41) T28 through evolutionary descent. The NucS Thr74Ile (c.C221T) polymorphism was identified as a key driver of this process in the Mabs homologous system.</div></div><div><h3>Conclusions</h3><div>These findings highlight the existence of globally disseminated clinical Mabs mutator clone with a potential increase in drug-resistance mutations affected by NucS Thr74Ile polymorphism, indicating an urgent need for novel therapies and enhanced community surveillance.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107677"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145633106","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":"SU3327: A multi-target compound targeting bacterial menaquinone and DNA","authors":"Shuge Wang ,&nbsp;Ke Zhao ,&nbsp;Ziqi Chen ,&nbsp;Chengtao Sun ,&nbsp;Hongliang Chen ,&nbsp;Yang Wang ,&nbsp;Congming Wu ,&nbsp;Dejun Liu","doi":"10.1016/j.ijantimicag.2025.107679","DOIUrl":"10.1016/j.ijantimicag.2025.107679","url":null,"abstract":"<div><h3>Objectives</h3><div>The rapid emergence of antibiotic resistance (AMR) threatens global health by rendering existing antibiotics ineffective, demanding novel antimicrobial agents with unique mechanisms of action. SU3327 (also known as Halicin), identified through deep learning-based drug screening, has demonstrated broad-spectrum antibacterial activity and high safety in vivo. However, its precise mechanism of action remains unclear. This study aimed to elucidate the antibacterial mechanism of SU3327 and to explore its potential as a multi-target therapeutic.</div></div><div><h3>Methods</h3><div>We employed microbiological, biochemical/biophysical, mass spectrometry, electrochemical, and transcriptomic analyses to study SU3327′s effects. We examined its impact on proton motive force (PMF), intracellular ATP synthesis, and electron transport chain (ETC) function, including Complex I inhibition and menaquinone interaction. We also evaluated nitroreductase bioactivation, identified the hydroxylamine metabolite, and quantified resulting oxidative DNA damage.</div></div><div><h3>Results</h3><div>SU3327 disrupts bacterial energy metabolism by targeting menaquinone (MK) in the ETC. It inhibits Complex I, impeding electron transfer, disrupting the PMF, and impairing ATP synthesis. Additionally, SU3327 enters <em>Escherichia coli</em> ATCC 25922, undergoing nitroreductase bioactivation, forming hydroxylamine compounds (R-NHOH) that react with DNA, generating hydroxyl radicals (•OH) and inducing oxidative DNA damage. These results indicate that SU3327 operates via a dual-target mechanism: disrupting bacterial respiration and causing DNA damage.</div></div><div><h3>Conclusions</h3><div>SU3327 is a first-in-class multi-target antibacterial agent acting via two synergistic mechanisms. Its dual action enhances efficacy and may reduce resistance likelihood by requiring mutations in distinct pathways. This study advances understanding of SU3327 and supports its development as a novel antibiotic for veterinary medicine.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107679"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145633182","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":"Phage therapy for KPC-producing Klebsiella pneumoniae decolonization in high-risk patients: The KIDNAP Study Protocol – A prospective feasibility and proof of concept study in the Brazilian context","authors":"Iris Najjar ,&nbsp;Larissa Simão Gandolpho ,&nbsp;Jôiciglecia Pereira dos Santos ,&nbsp;Camila de Paula Siqueira ,&nbsp;Ikechukwu B. Moses ,&nbsp;Ághata Cardoso da Silva Ribeiro ,&nbsp;Mélanie Roch ,&nbsp;Roberto Sierra ,&nbsp;Diego O. Andrey ,&nbsp;Celso Arrais-Rodrigues ,&nbsp;Ana C. Gales","doi":"10.1016/j.ijantimicag.2025.107673","DOIUrl":"10.1016/j.ijantimicag.2025.107673","url":null,"abstract":"<div><h3>Background</h3><div>There has been renewed interest in phages amidst growing antimicrobial resistance. Their potential for intestinal decolonisation is interesting because of their specificity, minimal side effects, and microbiota preservation. In addition, phage-resistant bacterial mutants that arise during treatment may become more susceptible to antibiotics and less virulent, possibly leading to better clinical outcomes.</div></div><div><h3>Objectives</h3><div>This study’s primary objective is to measure the efficacy of phage-based intestinal decolonisation of <em>Klebsiella pneumoniae</em> carbapenemase (KPC)-producing <em>K. pneumoniae</em> (KPC-Kp) at 14 days post-treatment, as well as its feasibility, which is defined as &gt;80% achieving at least 7 days of treatment. Secondary objectives will include phage safety at 14 days post-treatment, intestinal KPC-Kp load changes over time, characterisation of phage-resistant KPC-Kp mutants, microbiome changes, infection-related outcomes, and general clinical outcomes 3 months after the end of treatment.</div></div><div><h3>Methods</h3><div>This feasibility and proof-of-concept study aims to include 15 high-risk patients recruited from a tertiary hospital in São Paulo who will receive individualised phage combinations for a mean duration of 14 days. Safety data will be reviewed by an independent Safety Monitoring Board. Description of microbiological techniques is provided.</div></div><div><h3>Conclusions</h3><div>To the best of our knowledge, this is the first published protocol that aims to establish a standardised, individualised phage-treatment framework for intestinal decolonisation in a high-endemic setting. It will also explore phage-bacterial interactions and their broader impact on bacterial virulence and susceptibility profiles. It represents a stepping stone towards implementing phage therapy in South America and bringing knowledge and capacities to the countries most impacted by escalating antimicrobial resistance.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107673"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145581759","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":"Development and validation of machine learning models to predict vancomycin- and teicoplanin-associated acute kidney injury: A retrospective, multicenter study","authors":"Pin-Yi Lo ,&nbsp;Fan-Ying Chan ,&nbsp;Yi-En Ku ,&nbsp;San-Yuan Wang ,&nbsp;Hsiang-Yin Chen","doi":"10.1016/j.ijantimicag.2025.107651","DOIUrl":"10.1016/j.ijantimicag.2025.107651","url":null,"abstract":"<div><h3>Objective</h3><div>Despite the effectiveness of vancomycin and teicoplanin in managing Gram-positive infections, their nephrotoxicity may prolong hospitalization, and increase morbidity, mortality, and healthcare costs. This study aimed to develop and validate clinically applicable prognostic machine learning models for predicting vancomycin-associated acute kidney injury (VA-AKI) and teicoplanin-associated AKI (TA-AKI).</div></div><div><h3>Methods</h3><div>This retrospective study in Taiwan utilized the Taipei Medical University Clinical Research Database. Patients receiving intravenous vancomycin or teicoplanin therapy between February 2010 and December 2020 were included. Features were selected from 198 variables through recursive feature elimination using feature importance (RFECV) and SHapley Additive exPlanations importance (ShapRFECV). Twelve models were constructed using XGBoost and LightGBM. Model performance was assessed by eight evaluation metrics, including the area under the receiver operating characteristic curve (AUROC). The optimal threshold was determined based on the maximum F₁ score, and the SHAP analysis assisted in model interpretation.</div></div><div><h3>Results</h3><div>Among 9342 included patients, 19.70% (1383/7020) of patients in the training set, 18.58% (326/1755) in the internal validation set, and 20.5% (116/567) in the external validation set developed AKI. The XGBoost model, using features selected by ShapRFECV, demonstrated optimal predictive performance in both internal (AUROC 0.798, 95% confidence interval [CI] 0.791–0.804) and external (AUROC 0.779, 95% CI: 0.767–0.791) validation.</div></div><div><h3>Conclusions</h3><div>The XGBoost model, leveraging time-series data, accurately predicts AKI in vancomycin and teicoplanin users, supporting early risk assessment and personalized patient management. Future multicentre prospective external validation is needed to strengthen its real-world applicability and generalizability.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107651"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400702","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":"Structural and functional features of Klebsiella pneumoniae capsular degradation by the phage depolymerase KP32gp38: Implications for vaccination against K. pneumoniae","authors":"Valeria Napolitano ,&nbsp;Mario Privitera ,&nbsp;Zuzanna Drulis-Kawa ,&nbsp;Daniela Marasco ,&nbsp;Silvia Fallarini ,&nbsp;Rita Berisio ,&nbsp;Flavia Squeglia","doi":"10.1016/j.ijantimicag.2025.107596","DOIUrl":"10.1016/j.ijantimicag.2025.107596","url":null,"abstract":"<div><h3>Objective</h3><div><em>Klebsiella pneumoniae Przondovirus</em> KP32 presents a complex capsular degradation machinery comprised of two serotype-specific depolymerases, KP32gp38 and KP32gp37.</div></div><div><h3>Methods</h3><div>In this work, we performed capsular polysaccharide (CPS) degradation assays combined with mass spectrometry approaches to identify the reaction product of K21 serotype CPS degradation by KP32gp38. We determined the crystal structure of the KP32gp38 depolymerase in complex with the identified degradation product, a pyruvated pentasaccharide, called K21-pyr5.</div></div><div><h3>Results</h3><div>The structure showed that K21-pyr5 binds to the inter-chain catalytic site, allowing the identification of important residues for CPS recognition. Importantly, we observed that the production of K21-pyr5 through CPS degradation by KP32gp38 is able to induce the maturation and differentiation of monocyte-derived dendritic cells, which, in turn, induce lymphocyte proliferation and Th polarization. By employing a T7 phage of <em>Escherichia coli</em> analogy, we were able to provide insights into the portal assembly of the <em>Przondovirus</em> K32. Our modeling studies suggest that the KP32 portal, attached to its icosahedral capsid shell, carries 12 depolymerase molecules on a single virion, arranged in 6 branches; in each branch, KP32gp38 depolymerase adheres to KP32gp37, which is directly connected to the phage portal.</div></div><div><h3>Conclusions</h3><div>Overall, our results suggest that depolymerases act as anti-virulent agents, not only by depleting the bacteria of their CPS but also by producing immunostimulatory CPS degradation products. This indicates the use of CPS degradation products by depolymerases as potential antigens in <em>K. pneumoniae</em> vaccination strategies.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107596"},"PeriodicalIF":4.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953172","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":"Corrigendum to “Disrupting bacterial metabolism by targeting LDH reverses Streptococcus suis aminoglycoside resistance” [International Journal of Antimicrobial Agents 66/6 (2025) 1-16/107599]","authors":"Shuji Gao ,&nbsp;Yingying Quan ,&nbsp;Shenao Song ,&nbsp;Wenjie Jin ,&nbsp;Zhiheng Chang ,&nbsp;Baobao Liu ,&nbsp;Yuxin Wang ,&nbsp;Li Yi ,&nbsp;Yang Wang","doi":"10.1016/j.ijantimicag.2025.107631","DOIUrl":"10.1016/j.ijantimicag.2025.107631","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107631"},"PeriodicalIF":4.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274431","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":"Pharmacodynamic insights to support pneumonia treatment in a patient co-infected with two carbapenem-resistant bacteria","authors":"Brooke N. Curry ,&nbsp;Nidhi Singh ,&nbsp;Alan E. Gross ,&nbsp;Jackson V. Watkins ,&nbsp;Egon A. Ozer ,&nbsp;Arunkumar Karunanidhi ,&nbsp;Kayley Sherwood ,&nbsp;Osayamen Obanor ,&nbsp;Nahed Ismail ,&nbsp;Alan R. Hauser ,&nbsp;Zackery P. Bulman","doi":"10.1016/j.ijantimicag.2025.107633","DOIUrl":"10.1016/j.ijantimicag.2025.107633","url":null,"abstract":"<div><div>Identifying optimal antibiotic therapy for patients infected with extensively resistant bacteria is challenging, particularly when there are multiple organisms at the infection site. Personalized time-kill assays (TKAs) can be used to test the pharmacodynamic activity of clinically relevant antibiotic combinations to help select appropriate therapy for these difficult-to-treat infections. We report a case of ventilator-associated pneumonia due to <em>Pseudomonas aeruginosa</em> and <em>Providencia stuartii</em> that were each carbapenem resistant<em>.</em> Due to the complex resistance phenotypes, the isolates were analysed via TKAs during the patient’s hospitalization to evaluate the activity of relevant antibiotic combinations. Using the patient’s isolates, the TKAs showed that a combination of ceftazidime/avibactam and a polymyxin was synergistic against the <em>P. aeruginosa</em> whereas ceftazidime/avibactam plus aztreonam was slightly more active than ceftazidime/avibactam alone against the <em>P. stuartii.</em> The results of the TKAs helped to validate the patient’s treatment regimen of aztreonam, ceftazidime/avibactam, and colistin (inhaled), which successfully treated the infection. Whole genome sequencing later revealed that the <em>P. stuartii</em> harbored a <em>bla</em>_OXA-48 carbapenemase while the mechanism of carbapenem resistance in the <em>P. aeruginosa</em> was likely due to OprD loss combined with extended-spectrum β-lactamase expression. The putative mechanism of cefiderocol resistance in the <em>P. stuartii</em> isolate was identified as a premature stop codon in the <em>cirA</em>-like gene combined with the presence of β-lactamases. The patient’s carbapenem-resistant coinfection was successfully treated with agents that were validated in real time using personalized TKAs. TKAs may be useful to optimize combination antibiotic therapy for patients infected with extensively resistant bacteria.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107633"},"PeriodicalIF":4.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182151","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}