JAC-Antimicrobial Resistance最新文献

{"title":"First-in-human study of the benzothiazinone and DprE1 inhibitor BTZ-043, a novel drug candidate for the treatment of Tuberculosis.","authors":"Wandini Lutchmun, Norbert Heinrich, Elin M Svensson, Florian Kloss, Sarah Konsten, Julia Dreisbach, Michael Hoelscher","doi":"10.1093/jacamr/dlaf127","DOIUrl":"10.1093/jacamr/dlaf127","url":null,"abstract":"<p><strong>Objectives: </strong>This first-in-human, single ascending dose study evaluated the safety, tolerability and pharmacokinetics (PK) of the decaprenylphosphoryl-β-D-ribose-2'-epimerase (DprE1) inhibitor BTZ-043.</p><p><strong>Methods: </strong>BTZ-043 was administered as an oral suspension at doses of 125, 250 and 500 mg along with placebo to healthy participants. Safety assessments included evaluation of laboratory parameters, vital signs, physical and neurological examination, and 12-lead ECG. Blood samples for PK assessment in plasma were collected over a 36 h post-dose period. PK parameters were calculated using non-compartmental analysis for parent BTZ-043, metabolites M1 and M2, and BTZ-043_total (sum of BTZ-043 and M2) in plasma.</p><p><strong>Results: </strong>Thirty participants completed the study. All administered BTZ-043 doses were safe and well tolerated. Nervous system disorders (dizziness and headache) and vascular disorders (hypertension and hot flush) were the most frequently reported adverse events (AEs). All AEs were mild or moderate. The parent compound BTZ-043 was rapidly metabolized to metabolite M2 (unknown activity), with median time to maximum concentration in plasma (<i>t</i> _max) of 1.5 h (1-2 h). BTZ-043 and M2 had a short half-life. The second main inactive metabolite M1 showed a median <i>t</i> _max of 7-8.5 h and a geometric mean half-life of 8.4-9.0 h. The increases in AUC and maximum concentration of drug in plasma (<i>C</i> _max) of BTZ-043 were more than dose-proportional, and those of BTZ-043_total were almost dose-proportional. No relevant differences in systemic exposures between males and females were observed.</p><p><strong>Conclusions: </strong>BTZ-043 was safe, well tolerated and underwent rapid absorption, metabolism and elimination, supporting further clinical development.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf127"},"PeriodicalIF":3.3,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial resistance burden landscape in Germany in 2019: a comparative country-level estimation.","authors":"Tomislav Meštrović, Sebastian Haller, Gisela Robles Aguilar, Annika Meinen, Anna Gershberg Hayoon, Christine Geffers, Achim Dörre, Muna Abu Sin, Authia P Gray, Lucien R Swetschinski, Kevin S Ikuta, Erin Chung, Eve E Wool, Chieh Han, Daniel T Araki, Rebecca Hsu, Christiane Dolecek, Tim Eckmanns, Mohsen Naghavi","doi":"10.1093/jacamr/dlaf142","DOIUrl":"10.1093/jacamr/dlaf142","url":null,"abstract":"<p><strong>Objectives: </strong>Our aim was to present the most comprehensive set of pre-COVID-19 antimicrobial resistance (AMR) burden estimates for Germany to date, with a focus on regional variations and hotspots.</p><p><strong>Methods: </strong>The study estimated deaths and disability-adjusted life-years (DALYs) due to AMR for 23 bacterial pathogens and 88 pathogen-drug combinations in Germany in 2019, with the use of two counterfactual scenarios: deaths attributable to AMR (those that would not have occurred if infections were susceptible) and deaths associated with AMR (cases where AMR was present but not necessarily the cause of death). Models were cross-validated for out-of-sample predictive validity, and uncertainty intervals (UIs) calculated. In stratified analyses we compared death estimates and DALYs with previously published estimates.</p><p><strong>Results: </strong>The total burden of mortality and DALYs associated with AMR in Germany were 45 692 (95% UI, 31 281-64 591) deaths and 752 697 (500 313-1 076 187) DALYs, respectively, with the total burden attributable to AMR 9648 (6520-13 918) deaths and 159 032 (105 021-232 459) DALYs, respectively. Bloodstream, respiratory and intra-abdominal infections were the major contributors to the fatal AMR burden. The leading pathogens responsible for AMR-associated deaths were <i>Escherichia coli</i>, <i>Staphylococcus aureus</i>, <i>Enterococcus faecium</i>, <i>Klebsiella pneumoniae</i> and <i>Pseudomonas aeruginosa</i>. <i>E. coli</i> resistant to β-lactam/β-lactamase inhibitors and aminopenicillin were top pathogen-drug combinations causing deaths attributable to and associated with AMR, respectively. The presented estimates align with previous research.</p><p><strong>Conclusions: </strong>The high resistance levels and significant health burden highlight AMR as a serious public health challenge in Germany, emphasizing the need to further strengthen targeted prevention and control measures against key pathogen-drug combinations.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf142"},"PeriodicalIF":3.3,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of oral fluoroquinolones in France between 2014 and 2023: a nationwide drug utilization study.","authors":"Daniele Saade, Marie-Joelle Jabagi, Marion Bertrand, Karima Hider-Mlynarz, Lamiae Grimaldi, Mahmoud Zureik","doi":"10.1093/jacamr/dlaf145","DOIUrl":"10.1093/jacamr/dlaf145","url":null,"abstract":"<p><strong>Objectives: </strong>This study describes fluoroquinolone (FQ) use and trends in France from 2014 to 2023, amid efforts to curb resistance and adverse effects.</p><p><strong>Methods: </strong>A nationwide observational study was conducted using data from the French National Health Insurance Database. All individuals with at least one reimbursed outpatient prescription for oral FQs between 2014 and 2023 were included. Annual cross-sectional data described prescriptions, user demographics and prescriber specialties. Trends and variations in FQ use were assessed by percent changes and compound annual growth rates. Age- and sex-standardized incidence rates (IRs) of FQ use were calculated.</p><p><strong>Results: </strong>FQ use declined by 50% from 2014 to 2023, with users dropping from 3.5 to 1.7 million and prescriptions from 4.8 to 2.2 million. Users mean age increased from 54.8 to 58.2 years, and the female proportion fell from 68% to 51%. FQ use dropped by 40% in those aged 60+  and 60% in younger individuals. Standardized IRs dropped from 54.9 to 25.6 per 1000 person-years. From 2014 to 2023, ofloxacin, ciprofloxacin, levofloxacin and moxifloxacin use decreased by 40%, 22%, 5% and 72%, respectively. Norfloxacin and lomefloxacin use dropped by 86% and 79% from 2014 to 2019, the year their reimbursement ended. General practitioners were the primary prescribers, accounting for 82.9% of prescriptions in 2023, followed by urologists-nephrologists (6.1%), ophthalmologists (1.6%), otolaryngologists (1.2%) and gynaecologists (1.1%).</p><p><strong>Conclusions: </strong>FQ use in France has declined significantly over the past decade, driven by awareness efforts and guideline changes, but remains high compared with other European countries, highlighting the need for ongoing stewardship.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf145"},"PeriodicalIF":3.3,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Penicillin allergy de-labelling implementation intervention in a UK hospital: a process evaluation, the patient experience.","authors":"Neil Powell, Mathew Upton, Bridie Kent, Jonathan A T Sandoe, Sarah Tonkin-Crine","doi":"10.1093/jacamr/dlaf144","DOIUrl":"10.1093/jacamr/dlaf144","url":null,"abstract":"<p><strong>Background: </strong>Penicillin allergy (penA) records are common, but true penA is rare. PenA records are associated with broad spectrum antibiotic prescribing and negative patient outcomes. We developed a behavioural intervention package to support inpatient penicillin allergy de-labelling (PADL) delivered by a multi-profession non-allergist workforce to remove incorrect penA records from medical and surgical adult inpatients in a UK hospital.</p><p><strong>Aims: </strong>To explore the experiences, beliefs and concerns of patients who had been offered PADL.</p><p><strong>Methods: </strong>Semi-structured interviews to explore the views of patients admitted to a medical or surgical ward with a penA record and offered PADL between June 2024 and October 2024. Inductive reflexive thematic analysis was used to analyse the data.</p><p><strong>Results: </strong>Twenty patients were interviewed. Patients that believed their penA to be incorrect and those that described their index reaction as mild were more likely to agree to testing. Patients considered hospital a safe place to be tested. Some patients thought being acutely unwell was not a barrier to testing, whereas others preferred an outpatient setting once discharged from hospital. De-labelled patients described having a good explanation of the risks and benefits of PADL, were grateful for the opportunity and trusted the healthcare worker and the PADL process.</p><p><strong>Conclusion: </strong>PADL was well accepted by patients who described receiving a good explanation of the PADL process. Index reactions perceived as low severity (e.g. non-severe rashes) and/or doubtful of their penA (e.g. unaware they had a penA record) were more likely to accept PADL. Some who declined inpatient PADL would consider outpatient testing once recovered from their acute illness.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf144"},"PeriodicalIF":3.3,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144846533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of Frailty Index Laboratory in predicting clinical outcomes in patients with <i>Clostridioides difficile</i> infections: a 2020-24 single-centre retrospective study.","authors":"Giulia Patti, Nicola Veronese, Nicolò De Gennaro, Elda De Vita, Roberta Papagni, Carmen Pellegrino, Angela Amendolara, Vittorio Guerra, Alessandra Vigna, Vito Spada, Mariangela Cormio, Domenica Cassano, Giuliana Metrangolo, Luigi Ronga, Maria Chironna, Stefania Stolfa, Francesco Di Gennaro, Annalisa Saracino","doi":"10.1093/jacamr/dlaf143","DOIUrl":"10.1093/jacamr/dlaf143","url":null,"abstract":"<p><strong>Background: </strong><i>Clostridioides difficile</i> infection (CDI) is considered one of the most significant healthcare-associated infections with significant morbidity and mortality. Frailty, characterized by diminished physiological reserves, has emerged as a critical determinant of poor outcomes. The Frailty Index based on Laboratory tests (FI-Lab), derived from routine laboratory parameters, offers an objective tool for assessing frailty. The primary aim of this study was to assess the efficacy of FI-Lab in predicting mortality and recurrence in CDI hospitalized patients.</p><p><strong>Methods: </strong>This retrospective study analysed data from 280 patients diagnosed with CDI, hospitalized at the Policlinic of Bari between 2020 and 2024. Frailty was assessed using FI-Lab, based on 35 routine laboratory tests. Primary outcomes included 14- and 28-day mortality, recurrence during hospitalization and recurrence post-discharge. Associations between FI-Lab and outcomes were evaluated.</p><p><strong>Results: </strong>Of the 280 patients included, 213 survived and 67 died during hospitalization or within 28 days post-infection. Non-survivors had significantly higher FI-Lab scores compared to survivors (0.70 ± 0.15 versus 0.25 ± 0.12, <i>P</i> < 0.0001). FI-Lab demonstrated excellent discrimination for mortality at 14 and 28 days, with each 0.10-point increase in FI-Lab associated with elevated mortality risk. Predictive accuracy for recurrence was moderate (AUC = 0.73 for recurrence within 60 days post-discharge). Fidaxomicin use did not significantly reduce mortality or recurrence after adjustment for FI-Lab and comorbidities.</p><p><strong>Conclusions: </strong>FI-Lab is a predictor of mortality in CDI patients and a valuable tool for early risk stratification. Its utility in predicting recurrences is limited. Prospective studies are warranted to validate these findings and refine therapeutic approaches for high-risk patients.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf143"},"PeriodicalIF":3.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why antimicrobial resistance messaging fails: qualitative insights interpreted through the elaboration likelihood model.","authors":"Eva M Krockow, David R Jenkins, Samkele Mkumbuzi, Stephen J Flusberg, Carolyn Tarrant","doi":"10.1093/jacamr/dlaf148","DOIUrl":"10.1093/jacamr/dlaf148","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial resistance (AMR) is a global threat, yet public awareness remains low. This study examined perceptions of current AMR communications to improve knowledge, extending previous research through qualitative data analysed using the Elaboration Likelihood Model (ELM).</p><p><strong>Methods: </strong>We held 3 focus groups (<i>n</i> = 15) with UK patients with recent experience of AMR and 4 (<i>n</i> = 14) with hospital doctors experienced in AMR treatment and communication. Semi-structured questions explored perceptions of public AMR messaging. Data were analysed using reflexive thematic analysis.</p><p><strong>Results: </strong>Most participants found public AMR information difficult to access, overly technical, and unclear. They struggled to find personal and cultural relevance, described the tone as punitive and highlighted contradictory advice (e.g. discouraging antibiotic use while recommending full course completion), undermining argument quality. Some appreciated buzzwords like 'superbugs', but most felt that messages lacked impact and 'punch'. When viewed through the ELM, the problematic tone and lack of personalisation reduced recipients' motivation. The lack of readily available, clear information hindered their ability to engage deeply with messages via 'central route' processing, reducing the likelihood of elaboration and subsequent persuasion. Attitude change from peripheral route information processing was equally questionable given the lack of persuasive message cues.</p><p><strong>Conclusions: </strong>Current AMR messaging is insufficient and communication theory could highlight areas for improvement. Our ELM analysis suggests a need to enhance motivation, capability, and argument quality while adding persuasive, peripheral cues. Personally and culturally tailored messages with a positive, solution-focused tone and simplified, engaging language may boost impact and promote lasting attitude change.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf148"},"PeriodicalIF":3.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic and genotypic analysis of <i>Acinetobacter baumannii</i> isolated from combat wounds in Ukraine during 2022 and 2023.","authors":"V M Kondratiuk, Brendan T Jones, Ting L Luo, N S Fomina, Francois Lebreton, Jason W Bennett, Patrick Mc Gann, V P Kovalchuk","doi":"10.1093/jacamr/dlaf140","DOIUrl":"10.1093/jacamr/dlaf140","url":null,"abstract":"<p><strong>Background: </strong><i>Acinetobacter baumannii</i> is an important nosocomial pathogen worldwide. During the current invasion of Ukraine, reports of infections caused by this organism have proliferated. Here, we provide a phenotypic and genotypic analysis of <i>A. baumannii</i> associated with the conflict.</p><p><strong>Methods: </strong>Between March 2022 and September 2023, 68 <i>A. baumannii</i> strains were cultured from wounded Ukrainian service members in three hospitals in west-central Ukraine. Antibiotic susceptibility and WGS were performed on all isolates.</p><p><strong>Results: </strong>Strains encompassed eight different STs, including the emerging ST78 (and its single locus variant ST1077) and globally distributed ST2 lineages, with ST19 being the most common (25%). Fifty strains carried at least one acquired carbapenemase (<i>bla</i> _OXA-23 or <i>bla</i> _OXA-72), with seven strains carrying both. Overall, susceptibility ranged from 0% (fluoroquinolones) to 100% (SUL/durlobactam) and all strains had CST MICs <1 mg/mL. Notably, all but one ST2 isolates were resistant to FDC, and this correlated with the presence of the <i>bla</i> _PER-1 or <i>bla</i> _PER-7 ESBL genes. In contrast, 8 of 13 ST78 were FDC non-susceptible, but non-susceptibility was correlated with the disruption of the <i>pirA</i> siderophore receptor gene by IS<i>Aba35</i>. Finally, passage in MEM of one strain for 8 days resulted in a mutation of the <i>bla</i> _GES-11 ESBL to the <i>bla</i> _GES-14 carbapenemase.</p><p><strong>Conclusions: </strong>Sampling of <i>A. baumannii</i> strains infecting injured Ukrainian soldiers revealed the predominance of known (ST2) and emerging (ST19, ST78) lineages carrying carbapenemases. Antibiotic resistance was broad, including the recently approved catechol-substituted siderophore cephalosporin, FDC, highlighting the immense treatment challenges faced by medical personnel during this ongoing conflict.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf140"},"PeriodicalIF":3.3,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic characterization of azithromycin-resistant and extended-spectrum β-lactamase-producing <i>Shigella flexneri</i> 2a from two clinical isolates in Japan.","authors":"Yohei Kobayashi, Shuntaro Umeda, Kenichi Takahashi, Shinichiro Shibata, Keigo Shibayama, Masato Suzuki","doi":"10.1093/jacamr/dlaf136","DOIUrl":"10.1093/jacamr/dlaf136","url":null,"abstract":"","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf136"},"PeriodicalIF":3.3,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In vivo</i> evolution of ceftazidime-avibactam resistance in <i>bla</i> _OXA-244-positive <i>E. coli</i> potentially linked to PBP3 insertion and mutations in <i>acrB</i> and PBP2.","authors":"Kaan Kocer, Sébastien Boutin, Guido Hansen, Dennis Nurjadi, Niklas Maximilian Weidner","doi":"10.1093/jacamr/dlaf137","DOIUrl":"10.1093/jacamr/dlaf137","url":null,"abstract":"<p><strong>Background: </strong>Ceftazidime/avibactam has been introduced as a promising treatment option against multidrug-resistant Gram-negative bacteria.</p><p><strong>Objectives: </strong>To investigate the development of ceftazidime/avibactam resistance in a <i>bla</i> _OXA-48-like-carrying <i>Escherichia coli</i> strain with YRIK insertion in penicillin-binding protein 3 (PBP3).</p><p><strong>Methods: </strong>Eight clinical isolates were recovered from a single patient treated with ceftazidime/avibactam. The isolates were analysed using antimicrobial susceptibility testing, and WGS to identify potential resistance mechanisms. <i>In vitro</i> serial passage experiments with increasing ceftazidime/avibactam exposure were performed to model the <i>in vivo</i> resistance development. Quantitative RT-PCR was used to assess <i>acrB</i> mRNA expression.</p><p><strong>Results: </strong>Ceftazidime/avibactam resistance emerged during treatment, accompanied by significant increases in aztreonam/avibactam and avibactam MICs. All isolates, including those susceptible to ceftazidime/avibactam, had a YRIK insertion in PBP3. Additional mutations were identified in the AcrB efflux pump component and, in most cases in its regulatory genes and PBP2 in the resistant isolates. No significant differences in <i>acrB</i> expression levels were found between susceptible and resistant isolates, suggesting that structural changes in AcrB, rather than overexpression, are likely to contribute to resistance. Serial passage experiments confirmed these findings by demonstrating the emergence of mutations in the same genes under increasing ceftazidime/avibactam pressure.</p><p><strong>Conclusions: </strong>This study shows a complex resistance mechanism involving a YRIK insertion in PBP3, combined with mutations in AcrB and PBP2, as drivers of ceftazidime/avibactam resistance. These findings highlight the importance of monitoring <i>E. coli</i> isolates with YRIK insertions during ceftazidime/avibactam treatment and warrant further investigation into efflux pump-mediated resistance in Enterobacterales.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf137"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In vivo</i> pharmacokinetics, therapeutic efficacy and immune response of bacteriophage vB_AbaSt_W16 against carbapenem-resistant <i>Acinetobacter baumannii</i>.","authors":"Yoon-Jung Choi, Md Shamsuzzaman, Jae-Eon Lee, Yong Hyun Jeon, Hyungjin Kim, Young-Ran Yoon, Md Shohel Rana, Joohun Shin, Shukho Kim, Jungmin Kim","doi":"10.1093/jacamr/dlaf121","DOIUrl":"10.1093/jacamr/dlaf121","url":null,"abstract":"<p><strong>Background: </strong>The increasing prevalence of carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) infections necessitates alternative therapeutic strategies. Bacteriophage therapy has emerged as a promising approach, yet its clinical implementation is hindered by limited pharmacokinetic (PK) and pharmacodynamic (PD) data.</p><p><strong>Methods: </strong>The PK and PD properties of <i>Acinetobacter</i> phage vB_AbaSt_W16 were evaluated in a murine model. Systemic distribution, clearance kinetics and efficacy were assessed following oral (PO) and intraperitoneal (IP) administration. Conventional PK/PD analysis and real-time fluorescence imaging were used to examine <i>in vivo</i> phage dynamics.</p><p><strong>Results: </strong>After administration, vB_AbaSt_W16 rapidly disseminated systemically within 1 h, reaching peak concentrations at 8 h. Most tissues cleared the phage within 72 h, though residual amounts persisted in the spleen for up to 92 h. In a murine infection model, vB_AbaSt_W16 demonstrated potent antibacterial activity, reducing CRAB bacterial loads by 4-7 log₁₀ cfu/mL within 24 h. Compared with PO administration, IP administration resulted in higher systemic bioavailability and bacterial clearance. Fluorescence imaging enabled non-invasive, real-time monitoring of phage distribution, demonstrating its utility as a PK assessment tool. Notably, phage treatment did not trigger significant pro-inflammatory cytokine release (TNF-α, IL-6) in healthy mice and effectively reduced CRAB-induced inflammation.</p><p><strong>Conclusions: </strong>These findings highlight the therapeutic potential of vB_AbaSt_W16 and provide critical insights into its PK behaviour. The results support further clinical development of this phage for CRAB infections.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf121"},"PeriodicalIF":3.3,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}