{"title":"Fluctuations in copy number of the class A carbapenemase gene blaFRI appear to confer high-level carbapenem resistance.","authors":"Makiko Noda, Ayako Furuta, Shigeko Yashima, Daizo Yaguchi, Yoshihiko Kameyama, Yuba Inamine, Mari Matsui, Motoyuki Sugai, Satowa Suzuki","doi":"10.1093/jac/dkaf258","DOIUrl":"10.1093/jac/dkaf258","url":null,"abstract":"<p><strong>Objectives: </strong>French imipenemase (FRI) is a carbapenemase that confer a wide range of MICs of carbapenems in blaFRI-harbouring isolates. In some isolates, duplication of the blaFRI-containing region is reported with high carbapenem MICs. A clinical Enterobacter asburiae isolate harbouring blaFRI-9 on plasmid showed high-level carbapenem resistance. This study aimed to prove that this high-level carbapenem resistance is attributed to antimicrobial-induced duplication of blaFRI-9.</p><p><strong>Methods: </strong>Carbapenem-resistant and carbapenem-susceptible revertants derived from the clinical isolate were selected by culturing with and without antimicrobials, respectively. WGS was performed to identify the genetic background of those strains. The number of repeats of the 35 422-bp region surrounding blaFRI-9, designated as the FRI-9-long repeat region (FRI9-LR), was estimated by the ratio of the average sequence depth of FRI9-LR to that of other regions excluding FRI9-LR.</p><p><strong>Results: </strong>Revertants obtained by culturing with and without antimicrobials, resulting in strains with varying carbapenem MICs. WGS revealed correlation between the number of repeats of FRI9-LR and the carbapenem MICs. Exposing the carbapenem-susceptible revertant to ampicillin did not increase the number of FRI9-LR repeats and only minimally increased the carbapenem MICs, possibly due to overexpression of AmpC β-lactamase. However, exposure to meropenem after ampicillin significantly increased both the number of FRI9-LR repeats and the carbapenem MIC, resulting in multidrug resistance.</p><p><strong>Conclusions: </strong>The high-level carbapenem resistance in this clinical isolate was attributed to multiple duplications of FRI9-LR. Furthermore, the flexibility in the duplication of this region resulted in changes in antimicrobial susceptibility, without loss or acquisition of resistance genes.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2503-2512"},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707559","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}
Parul Patel, Ana Milinkovic, Richard Grove, Lindsay Govan, Michael McKenna, Brian Wynne, Cassidy Henegar, Esteban Martinez, Paul Dimondi, Ken Chow, Nassrin Payvandi, Bryn Jones
{"title":"Hypertension and blood pressure changes with dolutegravir or comparator antiretroviral therapy in randomized trials through 96 weeks.","authors":"Parul Patel, Ana Milinkovic, Richard Grove, Lindsay Govan, Michael McKenna, Brian Wynne, Cassidy Henegar, Esteban Martinez, Paul Dimondi, Ken Chow, Nassrin Payvandi, Bryn Jones","doi":"10.1093/jac/dkaf212","DOIUrl":"10.1093/jac/dkaf212","url":null,"abstract":"<p><strong>Background: </strong>To date, there are limited published data from randomized trials evaluating the effects of integrase strand transfer inhibitor-based regimens, including dolutegravir-based antiretroviral therapy (ART), on blood pressure (BP) in people with HIV-1 (PWH).</p><p><strong>Objectives: </strong>This analysis evaluated BP changes from baseline and incident hypertension among ART-naive PWH randomized to dolutegravir-based three-drug ART or alternative comparator ART (cART) across pooled Phase 2/3 studies.</p><p><strong>Methods: </strong>In this post hoc analysis of Phase 2/3 SPRING-1, SPRING-2, SINGLE and FLAMINGO clinical trials, BP was assessed at baseline, Week (W) 48 and W96. In PWH without evidence of hypertension at baseline, incident hypertension was defined as a single systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg measured after a 5 min rest, a hypertension adverse event and/or antihypertensive medication use during follow-up. Baseline factors associated with incident hypertension at W96 were assessed through multivariate analyses. BP changes between dolutegravir and cART were also assessed.</p><p><strong>Results: </strong>Among 2345 randomized participants, 1815 (77%) had no evidence of hypertension at baseline; 927 received dolutegravir-based ART and 888 received cART. Through W96, incident hypertension did not differ between groups [dolutegravir, 23% (n = 180/779); cART, 21% (n = 139/665); adjusted OR, 1.02; 95% CI, 0.79-1.33]; ∼1% of participants initiated antihypertensive medication through W96 (dolutegravir, n = 3; cART, n = 1). At W96, no significant BP changes from baseline were observed (systolic BP, P = 0.741; diastolic BP, P = 0.683).</p><p><strong>Conclusions: </strong>Relative to non-dolutegravir-containing cART, dolutegravir-containing three-drug ART did not show any impact on incident hypertension in ART-naive PWH without evidence of hypertension at baseline through W96.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2375-2383"},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comment on: Isavuconazole therapeutic drug monitoring and association with adverse events.","authors":"Mi Zhou, Chunhong Zhang, Xuben Yu","doi":"10.1093/jac/dkaf236","DOIUrl":"10.1093/jac/dkaf236","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2561-2562"},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731095","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":"Comment on: Outcomes of ceftriaxone 2 g versus 1 g daily in hospitalised patients with pneumonia: a nationwide retrospective cohort study.","authors":"Satoru Mitsuboshi","doi":"10.1093/jac/dkaf256","DOIUrl":"10.1093/jac/dkaf256","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2563"},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690300","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}
Rebecka Papaioannu Borjesson, Sara Diotallevi, Riccardo Lolatto, Giovanni Cenderello, Laura Comi, Antonio Cascio, Annalisa Saracino, Tommaso Clemente, Maria Mazzitelli, Sergio Lo Caputo, Daniele Armenia, Maria Mercedes Santoro, Antonella Castagna, Vincenzo Spagnuolo
{"title":"Persistence of CXCR4-tropic virus in people living with four-class drug-resistant HIV and its clinical impact in the modern antiretroviral era.","authors":"Rebecka Papaioannu Borjesson, Sara Diotallevi, Riccardo Lolatto, Giovanni Cenderello, Laura Comi, Antonio Cascio, Annalisa Saracino, Tommaso Clemente, Maria Mazzitelli, Sergio Lo Caputo, Daniele Armenia, Maria Mercedes Santoro, Antonella Castagna, Vincenzo Spagnuolo","doi":"10.1093/jac/dkaf211","DOIUrl":"10.1093/jac/dkaf211","url":null,"abstract":"<p><strong>Background: </strong>CXCR4-tropic HIV seems to be associated with more clinical events than CCR5-tropic virus.</p><p><strong>Objectives: </strong>This study aims to describe the effect of the persistence of CXCR4-tropic virus on the occurrence of clinical events in people with four-class drug-resistant HIV.</p><p><strong>Methods: </strong>This is a retrospective study on people with four-class drug-resistant HIV from the PRESTIGIO Registry, with at least two HIV-tropism determinations during follow-up. Follow-up accrued from the date of the first four-class drug resistance evidence (baseline) until death, loss to follow-up or freezing date (31 December 2023). Univariable Poisson regression was used to estimate and compare incidence rates of clinical events. Predictors of clinical events were assessed by multivariable Poisson regression.</p><p><strong>Results: </strong>A total of 144 people with four-class drug-resistant HIV [47 (33%) with persistent CXCR4-tropism, 39 (27%) with persistent CCR5-tropism and 58 (40%) with a tropism switch during follow-up] were included with a median follow-up of 7.80 years (IQR = 5.80-10.6). Overall, 117 (81.3%) 4DR-PLWH experienced at least one clinical event during follow-up [incidence rate = 32.5 (95% CI = 29.3-35.9)]. The persistence of CXCR4-tropic virus was associated with an increased risk of HIV-related events among people living with four-class drug-resistant HIV, even in modern ART era. After adjusting for age, sex at birth and CD4+/CD8+ at baseline, standardized viremia copy-years [adjusted-incidence rate ratio = 1.66 (95% CI = 1.24-2.26), P < 0.001] and persistent CXCR4-tropism [adjusted-incidence rate ratio: 2.01 (95% CI = 1.04-3.91), P = 0.037] were associated with the occurrence of HIV-related events.</p><p><strong>Conclusions: </strong>Our findings confirm CXCR4-tropism as a marker of HIV progression also in the four-class drug-resistant population, suggesting the need of further prioritization of viro-immunological control and studies of pathogenic mechanisms in presence of CXCR4-tropic multidrug-resistant viral strains.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2369-2374"},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690354","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}
Yongseop Lee, Jaeeun Seong, Jung Ah Lee, Jin Young Ahn, Su Jin Jeong, Nam Su Ku, Jun Yong Choi, Joon-Sup Yeom, Jung Ho Kim
{"title":"Comparing the mortality of patients with sepsis using empirical piperacillin/tazobactam and cefepime: analysis of the MIMIC-IV database.","authors":"Yongseop Lee, Jaeeun Seong, Jung Ah Lee, Jin Young Ahn, Su Jin Jeong, Nam Su Ku, Jun Yong Choi, Joon-Sup Yeom, Jung Ho Kim","doi":"10.1093/jac/dkaf254","DOIUrl":"10.1093/jac/dkaf254","url":null,"abstract":"<p><strong>Objectives: </strong>We compared the effectiveness of piperacillin/tazobactam and cefepime as empirical antibiotics for sepsis.</p><p><strong>Patients and methods: </strong>This retrospective cohort study included adult patients diagnosed with sepsis, receiving either piperacillin/tazobactam or cefepime as empirical treatment. Relevant data were extracted from the Medical Information Mart for Intensive Care IV database. Stabilized inverse probability of treatment weighting was used to adjust for the imbalance in covariates between both groups. The primary outcome was 90-day mortality, and Clostridium difficile infection and vancomycin-resistant enterococci colonization rates were the secondary outcomes.</p><p><strong>Results: </strong>Among 2485 eligible patients, 1161 received piperacillin/tazobactam and 1324 received cefepime as empirical treatment for sepsis. After stabilized inverse probability of treatment weighting, 90-day mortality did not significantly differ between the groups. The Kaplan-Meier curve showed no difference in 90-day mortality between the two groups (log-rank test, P = 0.947). Similarly, the rate of C. difficile infection and vancomycin-resistant enterococci colonization did not significantly differ.</p><p><strong>Conclusions: </strong>No significant difference was observed in the risk of mortality in the empirical use of either antibiotic, suggesting comparable efficacy in sepsis. Therefore, individual patient characteristics should be considered when treating sepsis rather than systematically recommending antibiotics.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2487-2495"},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Del Monte, S Kaleci, J Chester, V Zerbato, M Remitti, A Tili, A Dessilani, I Baldisserotto, S Esperti, M D Di Trapani, G Orlando, S Casolari, A Catania, A Bedini, E Franceschini, M Sarti, C Venturelli, I Venturelli, L Rofrano, E Ricchizzi, S Di Bella, C Mussini, M Meschiari
{"title":"Impact of vancomycin resistance on attributable mortality among Enterococcus faecium bloodstream infections: propensity score analysis of a large, multicentre retrospective study.","authors":"M Del Monte, S Kaleci, J Chester, V Zerbato, M Remitti, A Tili, A Dessilani, I Baldisserotto, S Esperti, M D Di Trapani, G Orlando, S Casolari, A Catania, A Bedini, E Franceschini, M Sarti, C Venturelli, I Venturelli, L Rofrano, E Ricchizzi, S Di Bella, C Mussini, M Meschiari","doi":"10.1093/jac/dkaf242","DOIUrl":"10.1093/jac/dkaf242","url":null,"abstract":"<p><strong>Background: </strong>Conflicting results exist about mortality risk of infections caused by vancomycin-susceptible Enterococcus faecium (VSEfm) and vancomycin-resistant Enterococcus faecium (VREfm). Our aim was to compare risk factors and clinical outcomes among patients with VSEfm and VREfm bloodstream infections (BSIs).</p><p><strong>Methods: </strong>A retrospective, multicentre, cohort study enrolled consecutive adult patients with VSEfm and VREfm BSI diagnosis between 2018-2022. Primary outcomes were 30-day-attributable and 30-day-overall mortality. Multivariable analysis propensity-weighted adjusted for timing to active therapy, Pitt Bacteremia Score (PBS) and Charlson Comorbidity Index (CCI) were performed to identify variables independently associated with 30-day mortality.</p><p><strong>Results: </strong>Overall, 446 patients were enrolled: 140 (31.4%) VREfm and 306 (68.6%) VSEfm. Comparatively, VREfm patients more frequently received inappropriate antibiotic therapy, had higher sequential organ failure assessment, PBS and BSI relapses. 30-day-attributable and 30-day-overall mortality did not differ significantly between the two groups. Independent risk factors for 30-day attributable mortality were age (HR 1.04, CI95%, 1.00-1.08, P = 0.022), corticosteroid therapy (HR 3.05, CI95%, 1.24-7.47, P = 0.014) and septic shock (HR 9.10, CI95%, 3.80-21.79, P≤0.001), and overall mortality were age (HR 1.04, CI95%, 1.02-1.05, P≤0.001.), chronic liver failure (HR 1.67, CI95%, 1.02-2.75, P = 0.04) and haematological disease (HR 2.25, CI95%, 1.28-3.94, P = 0.005). Vancomycin resistance is not an independent risk factor for mortality when data are adjusted for confounding factors.</p><p><strong>Conclusions: </strong>Adjusted analyses for time to active antibiotic therapy suggest that vancomycin resistance is not an independent risk factor for overall or attributable mortality among patients with Enterococcus faecium BSI. Independent risk factors identified in this study were exclusively comorbidities, severity and corticosteroids use.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2466-2473"},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diana Imoli, John M Maingi, Cecilia Mbae, Susan M Kavai, Celestine Wairimu, Sheilla Mundalo, Georgina Odityo, Mary Wairimu, Zelalem Mekuria, Wondwossen Gebreyes, Samuel Kariuki
{"title":"Genomic characterization of multidrug-resistant extended-spectrum β-lactamase-producing Vibrio cholerae O1 strains from 2022 cholera outbreak in Kenya.","authors":"Diana Imoli, John M Maingi, Cecilia Mbae, Susan M Kavai, Celestine Wairimu, Sheilla Mundalo, Georgina Odityo, Mary Wairimu, Zelalem Mekuria, Wondwossen Gebreyes, Samuel Kariuki","doi":"10.1093/jac/dkaf224","DOIUrl":"10.1093/jac/dkaf224","url":null,"abstract":"<p><strong>Background: </strong>In mid-2021, a global surge in cholera cases was reported. This study characterized Vibrio cholerae O1 isolates obtained from faecal samples of cholera-positive cases during the 2022 cholera outbreak in Kenya.</p><p><strong>Methods: </strong>A total of 202 V. cholerae were confirmed through serogroup and serotype characterization by slide agglutination. Susceptibility testing was done using the Kirby-Bauer disc diffusion method, and ESBL production confirmed using the double-disc synergy test. WGS was performed on Illumina and ONT platforms, followed by bioinformatics analysis.</p><p><strong>Results: </strong>All the isolates were identified as V. cholerae O1 of Ogawa serotype, with 99% classified as MDR and 98.5% positive for ESBL production. Notably, the isolates were resistant to azithromycin, one of the recommended antibiotics for cholera treatment. MDR was linked to the acquisition of an IncC plasmid (pVCMLK181) carrying seven resistance genes, including mph(A), mph(E) and msr(E), which confer resistance to azithromycin, and the blaPER-7 ESBL gene. Resistance to nalidixic acid was associated with mutations in QRDRs of gyrA and parC. The isolates also carried SXT/R391-like ICE, ICEVchInd5 featuring a 10 kb deletion and mapped to the 7PET-AFR13 lineage. Phylogenetic analysis revealed a close relationship to other highly drug-resistant AFR13 strains reported in Tanzania, Comoros and Mayotte.</p><p><strong>Conclusions: </strong>The high prevalence of multidrug resistance in cholera isolates emphasizes the need for continuous surveillance to monitor the evolution of MDR V. cholerae O1 strains and calls for consideration of deployment of alternative management and prevention options including oral cholera vaccines and long-term improvement of water, sanitation and hygiene (WASH) infrastructure and practice.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2399-2407"},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}