Journal of Antimicrobial Chemotherapy最新文献

{"title":"A multicentre real-life prospective cohort study on effectiveness, durability and safety of long-acting injectable cabotegravir and rilpivirine in northern Italy: the LONGITUDE study.","authors":"Maria Mazzitelli, Claudia Cozzolino, Dina Yaacoub, Angela Pieri, Elke Erne, Cinzia Puzzolante, Beatrice Fontana, Maddalena Giglia, Claudio Rigamonti, Maddalena Cordioli, Chiara Zanchi, Giada Fasani, Emanuela Lattuada, Giuliana Battagin, Stefano Nicolè, Marina Malena, Maria Cristina Rossi, Daniela Piacentini, Francesca Raumer, Vincenzo Scaglione, Massimiliano Lanzafame, Leonardo Calza, Cristina Mussini, Annamaria Cattelan","doi":"10.1093/jac/dkaf281","DOIUrl":"10.1093/jac/dkaf281","url":null,"abstract":"<p><strong>Objectives: </strong>We herein present a prospective multicentre experience of long-acting injectable (LAI) cabotegravir/rilpivirine from 11 different HIV clinics in northern Italy, focusing on the regimen's effectiveness, durability and safety in a real-life setting.</p><p><strong>Methods: </strong>We included all people who received at least one dose of LAI cabotegravir/rilpivirine, recording clinical data, and assessing factors associated with treatment discontinuation (TD) for any cause. Kaplan-Meier curves were used to estimate the probability of TD, and Cox regression models identified significant predictors of TD. A sub-analysis was conducted focusing on TD due to virological failure (VF, defined as two consecutive HIV-RNA values >200 copies/mL or a single value over 200 copies/mL leading to treatment withdrawal).</p><p><strong>Results: </strong>We included 483 participants (81.6% males) with a median age of 49 (IQR: 40-58) years. In 74.1% of participants, the LA regimen was started by choice, with 51.8% coming from a dual oral antiretroviral regimen. During a median follow-up time of 22 (IQR: 13-26) months, 54 (11.1%) participants had TD (incidence = 0.627 per 100 person-months of follow-up), mostly due to side effects (31, 6.4%) but with 7 (1.4%) due to VF [with people reporting major integrase strand transfer inhibitor (INSTI) and NNRTI resistance mutations in 71.4% cases]. When multivariable analysis was performed, age, years with HIV, CD4/CD8 ratio and BMI were significantly associated with TD. Also, we detected that the number of previous antiretroviral regimens was significantly associated with VF.</p><p><strong>Conclusions: </strong>Despite the overall effectiveness, TD was observed in a specific subset of people, primarily due to side effects, with a smaller proportion experiencing VF. Factors associated with both TD and VF underscore the importance of personalized selection to optimize LAI cabotegravir/rilpivirine outcomes and to improve regimen persistence.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2732-2741"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835181","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":"Horizontal transmission of a multidrug-resistant IncM1 plasmid harbouring blaOXA-48 and blaCTX-M-14b among patient microbiotas.","authors":"Roberto Sierra, Mélanie Roch, Julien Prados, Aude Nguyen, Abdessalam Cherkaoui, Gesuele Renzi, Jacques Schrenzel, Stephan Harbarth, Nicolas Vuilleumier, Diego O Andrey","doi":"10.1093/jac/dkaf228","DOIUrl":"10.1093/jac/dkaf228","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2876-2879"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659241","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":"From TRIO to one: simplification to bictegravir/emtricitabine/tenofovir alafenamide in highly treatment-experienced people living with MDR HIV.","authors":"José L Casado, José L Blanco, Isabel Izuzquiza, Ana Moreno, Pilar Vizcarra, Alejandro Vallejo","doi":"10.1093/jac/dkaf357","DOIUrl":"https://doi.org/10.1093/jac/dkaf357","url":null,"abstract":"<p><strong>Background: </strong>We evaluated the maintenance of virological suppression in people living with multidrug resistance (MDR) HIV (PLWH), who simplified to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF).</p><p><strong>Methods: </strong>We conducted a prospective, observational study of 62 PLWH with MDR who switched therapy because of drug-drug interactions (DDIs), non-adherence or toxicity. Survival analysis was used to assess the probability of virological failure (VF). Cumulative genotypic susceptibility score to BIC/FTC/TAF (cGSS; maximum 3 points) was evaluated.</p><p><strong>Results: </strong>Before the switch, PLWH were virologically suppressed for a median of 7.95 years (interquartile range, IQR, 2.5-9.7), 60% and 37% had resistance to two and three classes of antiretrovirals respectively (median cGSS = 2), and the mutation M184V/I was observed in 34 cases (68%). The main reason for switching was DDIs (61%). At Week 48, there were no VFs, three patients (5%) discontinued early due to mild neuropsychiatric events, and two showed transient detectable HIV RNA levels (1.8 and 1.85 log copies/mL). Thus, the efficacy was 91% (95% CI, 81%-99%, intention-to-treat analysis) and 94% (95% CI, 87%-100%, on-treatment). Total cholesterol and LDL cholesterol decreased significantly after the switch, and estimated glomerular filtration rate and tubular parameters remained stabilized. Excluding two diabetic PLWH with progressive renal deterioration, there were no VFs or additional discontinuations for 32.5 months (IQR, 14.1-48.5; follow-up, 199 person-years). By survival analysis, the probability of remaining on BIC/FTC/TAF was 91% at 5 years.</p><p><strong>Conclusions: </strong>In highly treatment-experienced PLWH harbouring MDR strains, who were virologically suppressed, switching to BIC/FTC/TAF was well tolerated with maintenance of virological control.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212304","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 activity of temocillin on ceftriaxone-resistant and ceftriaxone-susceptible isolates of Neisseria gonorrhoeae.","authors":"Julie Brousseau, François Caméléna, Fabienne Meunier, Anders Boyd, Thibault Chiarabini, Laure Surgers, Béatrice Berçot","doi":"10.1093/jac/dkaf235","DOIUrl":"10.1093/jac/dkaf235","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2879-2881"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753440","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":"Phenotypic and genotypic profiles of clinical isolates of various Nocardia species to carbapenems and fluoroquinolones.","authors":"Jing Yang, Tingfei Jiang, Mingrui Zhang, Jiaoyu Xue, Dongyan Shi","doi":"10.1093/jac/dkaf312","DOIUrl":"10.1093/jac/dkaf312","url":null,"abstract":"<p><strong>Objectives: </strong>To establish patterns of the antimicrobial susceptibility of Nocardia species to carbapenems and fluoroquinolones and analysis of phenotypic-genotypic correlations.</p><p><strong>Methods: </strong>Isolates were identified to the species using 16S rRNA, secA1, or rpoB gene sequencing analysis. The antimicrobial susceptibility testing was performed using the broth microdilution method, and WGS was employed to analyse the presence of resistance genes and/or mutations of Nocardia species against carbapenems and fluoroquinolones.</p><p><strong>Results: </strong>Among 143 Nocardia isolates, N. farcinica (27.27%, 39/143) and N. cyriacigeorgica (25.17%, 36/143) were the most common species, followed by N. abscessus Complex (18.88%, 27/143). The MIC90s of the seven carbapenems were 8 mg/L for doripenem, 8 mg/L for meropenem, 16 mg/L for ertapenem, 16 mg/L for biapenem, 64 mg/L for imipenem, 64 mg/L for faropenem and 128 mg/L for tebipenem, respectively. The susceptibility rates to imipenem were 76.9% and 88.9% for N. farcinica and N. cyriacigeorgica, respectively, but only 14.3% and 0% for N. otitidiscavarium and N. brasiliensis, respectively. Further, 90% of N. brasiliensis and 50% of N. otitidiscaviarum isolates were susceptible and intermediate to meropenem. WGS identified blaFAR-1 gene in N. farcinica and blaAST-1 gene in N. cyriacigeorgica, respectively. The MIC90s of the four fluoroquinolones were 1 mg/L for sitafloxacin, 4 mg/L for nemonoxacin, 4 mg/L for moxifloxacin and 16 mg/L for ciprofloxacin, respectively. The susceptibility rate of Nocardia species to ciprofloxacin was low except for N. farcinica. The resistance to fluoroquinolones arise from mutations in the gyrA gene.</p><p><strong>Conclusions: </strong>Nocardia spp. exhibited varying patterns of susceptibility to carbapenems and fluoroquinolones respectively. Importantly, different Nocardia spp. exhibited different patterns of susceptibility to carbapenems and fluoroquinolones, respectively.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2862-2872"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955061","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":"Population pharmacokinetics of bictegravir in real-world people with HIV.","authors":"Pierre Ekobena, Myriam Briki, Kim Dao, Catia Marzolini, Pascal Andre, Thierry Buclin, Matthias Cavassini, Monia Guidi, Paul Thoueille","doi":"10.1093/jac/dkaf297","DOIUrl":"10.1093/jac/dkaf297","url":null,"abstract":"<p><strong>Objectives: </strong>Bictegravir is an integrase strand transfer inhibitor widely prescribed due to its good efficacy and safety profile. Its pharmacokinetic (PK) profile has not been described in real-world settings yet. This study aimed to characterize bictegravir population PK in people with HIV (PWH) and to identify covariates affecting its disposition.</p><p><strong>Methods: </strong>Bictegravir concentrations were obtained from PWH as part of a therapeutic drug monitoring (TDM) follow-up performed at the Lausanne University Hospital, Switzerland, between July 2019 and July 2024. Demographic data, clinical data and co-medications were recorded during the routine Swiss HIV Cohort Study (SHCS) visits. A population PK model was developed using a non-linear mixed-effect approach with Monolix®.</p><p><strong>Results: </strong>A total of 708 steady-state plasma concentrations from 572 PWH were available for the analysis. A one-compartment model with first-order absorption and elimination best characterized bictegravir PK. Age and body weight were found to significantly affect bictegravir clearance, individuals of 51 years weighing 100 kg showing a 13% increase, and those aged 80 years weighing 70 kg a 11% decrease, relative to an individual weighing 70 kg and aged 51 years. These effects are not deemed clinically significant and do not warrant a clinical intervention.</p><p><strong>Conclusions: </strong>Considering the good safety and efficacy profile of bictegravir, routine TDM is of limited value for bictegravir. However, TDM of bictegravir could be beneficial in case of suspected viral resistance or non-adherence, in special subpopulations (i.e. obese individuals and pregnant women), or to monitor drug-drug interactions.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2782-2789"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835168","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":"Synergistic cefiderocol-containing antibiotic combinations active against highly drug-resistant Acinetobacter baumannii patient isolates with diverse resistance mechanisms.","authors":"Justin Halim, Andrew P Keane, Jeannete Bouzo, Tope Aderibigbe, Jessica A Chicola, Katie T Nolan, Keertana Jonnalagadda, Jason X Tran, Valerie J Carabetta","doi":"10.1093/jac/dkaf306","DOIUrl":"10.1093/jac/dkaf306","url":null,"abstract":"<p><strong>Background: </strong>Acinetobacter baumannii is a nosocomial pathogen known for rapidly developing resistance to nearly all antibiotics, including last-line agents. Cefiderocol, a novel siderophore cephalosporin, has shown in vitro activity against A. baumannii and is now used clinically, but resistance is emerging. Data on cefiderocol-based antibiotic combinations are limited.</p><p><strong>Objectives: </strong>To evaluate the in vitro activity of cefiderocol alone and in combination with other antibiotics against XDR and PDR A. baumannii clinical isolates, and to explore resistance mechanisms underlying cefiderocol synergy.</p><p><strong>Methods: </strong>We tested 21 XDR/PDR clinical isolates and one NDM-1-producing strain using broth microdilution and checkerboard assays with cefiderocol and 17 antibiotics, including ceftazidime/avibactam, sulbactam/durlobactam, and amikacin. Synergy was determined through checkerboard assays and calculating fractional inhibitory concentration indices (FICI). WGS was used to identify resistance genes in selected strains.</p><p><strong>Results: </strong>Cefiderocol alone was active against 66.7% of strains and demonstrated synergy with ceftazidime/avibactam and sulbactam/durlobactam in 100% and 95.2% of strains, respectively, and with amikacin, doxycycline and sulbactam in over half of strains. Cefiderocol-based combinations also reduced cefiderocol MICs against an NDM-1-producing strain. WGS revealed β-lactamases and resistance determinants among both susceptible and resistant isolates.</p><p><strong>Conclusions: </strong>Several cefiderocol-containing combinations show strong in vitro synergy against XDR and PDR A. baumannii. These combinations, especially cefiderocol-ceftazidime/avibactam and cefiderocol-sulbactam/durlobactam, may enhance treatment of highly resistant A. baumannii strains and warrant further clinical investigation.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2814-2824"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882865","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":"Distinct population structure and genomic context of NarAB between broiler and human clinical Enterococcus isolates.","authors":"Jayanth Balakuntla, Shabbir Simjee, Shrinivasrao P Mane, George Tice","doi":"10.1093/jac/dkaf296","DOIUrl":"10.1093/jac/dkaf296","url":null,"abstract":"<p><strong>Background: </strong>In recent years, reports have emerged linking the NarAB genes with elevated MICs to non-medically important ionophore coccidiostat class (specifically narasin, salinomycin and maduramycin) and potential co-selection of clinically relevant antibiotic resistance genes in Enterococcus faecalis and Enterococcus faecium.</p><p><strong>Methods: </strong>We analysed all publicly accessible E. faecalis (n = 7731) and E. faecium (n = 20 594) genomes, focusing specifically on the genomes from broiler-chicken, turkeys, dogs and human clinical infections.</p><p><strong>Results: </strong>The NarAB gene was more prevalent in broiler isolates (26% E. faecalis, 39.2% E. faecium) compared with human clinical isolates (2.8% E. faecalis, 2.0% E. faecium). In addition, genes associated with resistance to medically important antibiotics of clinical importance for E. faecalis and E. faecium infections were not found in the vicinity of the NarAB gene in isolates from broiler-chicken, and this refutes claims of the presence of co-selection between NarAB and medically important antibiotics. In addition, the pattern of genes near NarAB differed between broiler-chicken and human clinical isolates, as did the genomic sequence types isolated from each species.</p><p><strong>Conclusions: </strong>These findings indicate that E. faecalis and E. faecium from broiler-chicken are unlikely to contribute resistance genes to human clinical isolates, and this should continue to inform any policy that might limit poultry farmers' and veterinarians' access to ionophore coccidiostats in broiler-chicken.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2773-2781"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835186","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":"Characterization of blaOXA-542-mediated carbapenem resistance in Acinetobacter baumannii.","authors":"Jingchen Hao, Feng Lu, Ping Chen, Chengjie Ji, Na Li, Yue Xu, Yuehan Chen, Cuicui Liu, Jian Hu, Guocai Li","doi":"10.1093/jac/dkaf311","DOIUrl":"10.1093/jac/dkaf311","url":null,"abstract":"<p><strong>Background: </strong>Carbapenem-resistant Acinetobacter baumannii (CRAB) causes multiple anatomical site infections, representing a significant public health threat.</p><p><strong>Aim: </strong>This study reports the isolation and characterization of a carbapenem-resistant A. baumannii harbouring blaOXA-542, followed by a comprehensive investigation of its antimicrobial resistance mechanisms and genomic characteristics.</p><p><strong>Methods: </strong>Firstly, antimicrobial susceptibility testing was performed using the broth microdilution method. Subsequently, whole-genome sequencing was employed to identify and characterize the resistance and virulence determinants. The functional validation of resistance mechanisms was performed by gene knockdown and construction of expression vectors. The fitness cost of β-lactamase expression was identified by a bacterial growth kinetic test. Molecular docking was utilized to predict potential binding sites of β-lactamase and carbapenems. Finally, the genetic characteristics of the isolates were analysed through comparative genomics analyses and phylogenetic tree construction.</p><p><strong>Results and conclusions: </strong>The results demonstrated that blaOXA-542 confers resistance to carbapenem and penicillin in A. baumannii and Escherichia coli while exhibiting no significant impact on cephalosporins. The ability of blaOXA-542 to hydrolyze meropenem was further confirmed by modified carbapenem inactivation assay (mCIM). Expression of blaOXA-542 in E. coli BL21 showed no significant growth rate alteration. Comparative analysis of the blaOXA-542 genetic environment revealed a close association with Acinetobacter pitti. This study reports the emergence of blaOXA-542-mediated carbapenem and penicillin resistance in a novel A. baumannii lineage (ST2795Pas/ST3464Oxf), highlighting the urgent need for rational antibiotic use against specific pathogens.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2854-2861"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955128","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: Bactericidal activity of antibiotic combinations against clinical isolates of Enterococcus gallinarum and Enterococcus casseliflavus.","authors":"Karl Oldberg, Magnus Rasmussen","doi":"10.1093/jac/dkaf320","DOIUrl":"10.1093/jac/dkaf320","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2882-2883"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955143","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}