Journal of Antimicrobial Chemotherapy最新文献

{"title":"Correction to: Systematic reviews and the Journal of Antimicrobial Chemotherapy; past, present and future. A systematic reappraisal.","authors":"","doi":"10.1093/jac/dkaf403","DOIUrl":"https://doi.org/10.1093/jac/dkaf403","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355011","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":"Antifungal prophylaxis in patients with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD)-positive acute myeloid leukaemia receiving sorafenib during initial induction and consolidation treatment in ALLG AMLM16 trial.","authors":"Chin Fen Neoh, Michelle K Yong, Leesa Rowley, Andrew W Roberts, Glen A Kennedy, Simon He, Anthony P Schwarer, Ian A Bilmon, Andrew H Wei, Monica A Slavin","doi":"10.1093/jac/dkaf385","DOIUrl":"https://doi.org/10.1093/jac/dkaf385","url":null,"abstract":"<p><strong>Objectives: </strong>To report the rates of proven, probable and possible invasive fungal disease (IFD) in patients receiving antifungal prophylaxis during initial induction and consolidation treatment of acute myeloid leukaemia (AML) plus either sorafenib or placebo.</p><p><strong>Methods: </strong>As part of a randomized, double-blind trial of sorafenib or placebo in combination with intensive chemotherapy for newly diagnosed adult patients with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD)-positive AML (ALLG AMLM16 trial), liposomal amphotericin B (LAMB) prophylaxis was administered at 5 mg/kg twice weekly during induction and consolidation phases in both sorafenib and placebo treatment arms. Alternative prophylaxis was allowed per institutional practice once sorafenib/placebo treatment was completed. IFD episodes, reported as either a serious adverse event or an adverse event, were adjudicated.</p><p><strong>Results: </strong>Of the 94 patients included for analysis of IFD, four IFD episodes (one proven and three possible) were reported during the induction treatment phase. The overall rate of proven/probable/possible IFD was 4.3% (4/94), with rates of 3.1% (2/64) and 6.7% (2/30) in the sorafenib and placebo groups, respectively. Seven patients had infusion-related reactions, and four were reported to be associated with LAMB administration.</p><p><strong>Conclusions: </strong>LAMB with or without subsequent azole prophylaxis could be an alternative option for fungal prophylaxis for patients with AML in whom azoles are contraindicated or not tolerated. Sorafenib does not appear to be associated with an increased risk of IFD.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A prospective assessment of the efficacy and durability of long-acting cabotegravir and rilpivirine in individuals with HIV in Spain (RELATIVITY study).","authors":"Luis Buzón-Martín, Maria Luisa Montes, Roberto Pedrero, María José Galindo, Mireia Santacreu-Guerrero, María Remedios Alemán, Miguel Torralba, Alberto Díaz de Santiago, Fran Fanjul, Adrián Rodríguez, Alfonso Cabello, María José Crusells, María Del Carmen Navarro, María Aguilera, Carmen Hidalgo-Tenorio, Luis Emilio Morano-Amado, David Vinuesa, Carlos De Andres, Enrique Bernal-Morell, Rosa María Martínez-Álvarez, Noemí Cabello-Clotet, Juan Tiraboschi, María Del Carmen Montero, María Jesús Vivancos-Gallego, Cristina Díez, Ruth Calderón, Miguel Alberto De Zárraga, Laura Gisbert, Alberto Romero-Palacios, Rebeca Cabo, Josefa Francisca Soler, María Antonia Sepúlveda, Antonio Jesús Sánchez-Guirao, Cristina Escrich, Francisco Arnaiz De Las Revillas, Eva Ferreira, Beatriz Valentín, Ana Lérida, Jara Llenas-García, Albert Gómez, Juan Emilio Losa, Bárbara Alonso, José Sanz, Mar Masiá, Hadrian Pernas, Juan José Corte, María Ángeles Garcinuño, Juan Carlos Gainzarain, Miriam Estébanez, María Del Mar García-Navarro, Patricia Barragán, Noemí Ramos, Marta Clavero, Marta Millán, Míkel Del Álamo, Miguel Egido, Beatriz De La Calle, Oscar Luis Ferrero, Jesús Troya","doi":"10.1093/jac/dkaf389","DOIUrl":"https://doi.org/10.1093/jac/dkaf389","url":null,"abstract":"<p><strong>Background: </strong>Daily oral antiretroviral therapy (ART) has transformed HIV into a chronic, manageable condition, but it still poses psychological, logistical, and biological challenges. Long-acting injectable (LAI) cabotegravir plus rilpivirine provides an alternative for virologically suppressed individuals, reducing treatment fatigue, stigma, and daily dosing. While clinical trials have demonstrated efficacy and safety, real-world data remain limited. We assessed the effectiveness and safety of LAI cabotegravir plus rilpivirine in Spain.</p><p><strong>Methods: </strong>RELATIVITY is a 5-year, multicentre, ambispective, non-controlled cohort study. The primary endpoint was treatment effectiveness, defined as the proportion of patients discontinuing LAI therapy for any reason, including loss of virological suppression (HIV-RNA >50 copies/mL) during follow-up, regardless of formal failure criteria.</p><p><strong>Results: </strong>This interim analysis (cut-off: March 1, 2025) included 3203 patients from 58 Spanish hospitals; 57 were excluded due to detectable viral load at switch, leaving 3146 participants. Most were men (84.6%), with a median age of 45 years. Median time on ART before switching was 9.0 (5.0-15.0) years, and duration of viral suppression was 84.0 (36.0-132.0) months. Prior integrase inhibitor-based regimens were reported in 77.1%. Virological suppression was maintained in ≥96% through 23 months of follow-up. Overall, 6.4% (n = 199) discontinued, most frequently for injection-site reactions (n = 45), systemic adverse events (n = 29), or virological failure (n = 20).</p><p><strong>Conclusions: </strong>Interim results from the RELATIVITY cohort confirm high effectiveness and safety of LAI cabotegravir plus rilpivirine in Spanish clinical practice, consistent with randomized trial outcomes and real-world data. An extended follow-up will provide further insights.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345339","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":"Real-life use of isavuconazole in Spanish children and adolescents.","authors":"Natalia Mendoza-Palomar, Silvia Simó Nebot, Laura Roig-Soria, Laura Alonso García, Clara Izquierdo Anto, Marta Taida García Ascaso, David Díaz Pérez, Carlos Grasa Lozano, Cristina Jiménez Núñez, Elena María Rincón López, Maria Luisa Navarro Gómez, Begoña Carazo Gallego, Beatriz Álvarez Vallejo, Jose Tomás Ramos Amador, Ángela Manzanares, Beatriz Jiménez Montero, Antoni Noguera Julian, Pere Soler-Palacin","doi":"10.1093/jac/dkaf394","DOIUrl":"https://doi.org/10.1093/jac/dkaf394","url":null,"abstract":"<p><strong>Background and objectives: </strong>Isavuconazole (ISA) has been recently approved for the treatment of invasive aspergillosis and mucormycosis in patients aged >1 year. Prior to this approval, it was used in paediatric patients under compassionate use. The objective of this study is to describe the experience with ISA use in children.</p><p><strong>Patients and methods: </strong>A descriptive, retrospective, multicentre study conducted in nine Spanish hospitals, including patients aged ≤18 years who received ≥7 days of ISA between 2018 and 2023. Therapeutic drug monitoring (TDM) was performed with pre-dose [trough concentration (Ctrough)] levels measured according to local protocols. A therapeutic range of 2.5-5 mg/L was used for analysis.</p><p><strong>Results: </strong>A total of 107 patients (median age: 11 years, 56% male) were included. ISA was used as a treatment (95 patients), mostly as second-line therapy (64 patients, 67%), due to toxicity from previous antifungals (27 patients, 42%). Of 53 patients with proven/probable invasive fungal disease (IFD), 32 (60%) showed a favourable response and 21 (40%) died, 13 due to IFD. Twelve patients received ISA as prophylaxis and none developed breakthrough IFD. Overall, 27/107 (25%) patients experienced adverse effects, the most common being hepatotoxicity, with 10 requiring discontinuation. TDM was performed in 76/95 patients (80%), revealing 59% of Ctrough values outside the therapeutic range.</p><p><strong>Conclusions: </strong>ISA appears to be a safe and effective option for treating IFD in children, especially when first-line agents have failed or caused excessive toxicity. Although no correlation between Ctrough and clinical outcomes was observed, the significant proportion of patients with out-of-range Ctrough emphasizes the need for TDM in paediatrics.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345341","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":"Posaconazole enteral tube administration in adults: pharmacokinetic target attainment of oral suspension compared with crushed delayed-release tablet.","authors":"Nirjan Bhattarai, Ryan W Stevens, Patrick M Wieruszewski, Dan Ilges, John C Robinson, Kristin C Cole, Casey R O'Connell, Tanner M Johnson","doi":"10.1093/jac/dkaf396","DOIUrl":"https://doi.org/10.1093/jac/dkaf396","url":null,"abstract":"<p><strong>Background: </strong>Posaconazole immediate release (IR) suspension is the standard product for enteral feeding tube (EFT) administration but has erratic pharmacokinetic behaviour, often resulting in subtherapeutic concentrations. Limited evidence suggests that posaconazole oral delayed-release (DR) tablets may be crushed.</p><p><strong>Methods: </strong>This was a retrospective cohort study of hospitalized adults who received EFT administration of posaconazole IR suspension or crushed DR tablets between 2018 and 2024. Patients were eligible if they had at least one serum drug concentration drawn ≥5 days after posaconazole initiation. The primary outcome was attainment of therapeutic drug concentrations. Secondary outcomes included time to therapeutic serum concentration, adverse drug events, and frequency of occluded EFT.</p><p><strong>Results: </strong>Of the included patients, 48 received IR suspension and 100 received DR tablets. Baseline characteristics and severity of illnesses were well balanced. Among IR suspension and crushed DR tablet recipients, 39% and 80% achieved therapeutic concentrations, respectively (P = 0.002). After adjusting for age, sex, BMI, drug interactions, posaconazole indication and malabsorptive conditions, crushed DR tablets were significantly more likely than IR suspension to achieve therapeutic posaconazole concentrations within 30 days (HR 5.22, 95% CI 2.35-11.61). Occluded EFTs were more frequent among crushed DR tablet recipients (27% versus 10%, P = 0.022), while no differences were observed in the occurrence of hepatotoxicity or hypokalaemia.</p><p><strong>Conclusions: </strong>With EFT administration, crushed posaconazole DR tablets were associated with a greater likelihood of achieving therapeutic concentrations compared with IR suspension. The optimal technique for administering crushed DR tablets to prevent EFT complications warrants investigation.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345340","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":"Retrospective analysis of pharmacological therapeutic monitoring of caspofungin in patients undergoing continuous renal replacement therapy using polyacrylonitrile membranes.","authors":"Antoine Hérault, Jonathan Nicolas, Zoé Demailly, Fabienne Tamion, Dominique Vodovar","doi":"10.1093/jac/dkaf390","DOIUrl":"https://doi.org/10.1093/jac/dkaf390","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345342","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":"The Achilles' heel of the Trojan Horse? A systematic evaluation of cefiderocol susceptibility testing.","authors":"Deny Tsakri, Stefanos Ferous, Ioannis Baltas, Louis Grandjean, Cleo Anastassopoulou, Athanasios Tsakris","doi":"10.1093/jac/dkaf391","DOIUrl":"https://doi.org/10.1093/jac/dkaf391","url":null,"abstract":"<p><p>Cefiderocol, an innovative siderophore cephalosporin, presents a novel therapeutic option against a spectrum of multidrug-resistant (MDR) Gram-negative pathogens. Nevertheless, resistance remains a formidable challenge, particularly among metallo-beta-lactamase (MBL)-producing organisms. Accurate antimicrobial susceptibility testing (AST) for cefiderocol is complex due to the labour-intensive broth microdilution (BMD) reference method requiring iron-depleted media, lacking reproducibility. In response, commercial AST methods, including BMD panels, disc diffusion (DD), and gradient diffusion test, have been developed. Commercial BMD panels, such as ComASP® and UMIC®, demonstrate potential, with the latter reaching categorical agreement (CA) above 90%. Yet, essential agreement (EA) remains between 75% and 85%, below the 90% desired threshold, with very major errors (VMEs) occurring frequently (∼15%). Disc diffusion (DD) methods, while practical, often overcall resistance, leading to major errors (MEs) with a median across studies of 29%. Among disc manufacturers, MASTDISCS® performed best, with a pooled CA of 93.2%, 5.4% ME and 6.3% VME. Overall, discs recorded a CA of 79.4%, MEs of 29.0% and VMEs of 13.9%. Gradient diffusion tests performed least favourably among all methods, exhibiting a notably high VME rate of 41.1%, and their use should be limited. Cefiderocol AST is further complicated by disparities between European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI)/Food and Drug Administration (FDA) breakpoints, contributing to inconsistencies in susceptibility categorization across laboratories. Additional challenges, such as trailing endpoints and microcolonies within inhibition zones, further confound readings, especially in DD assays. Consequently, the standardization and rigorous validation of the best performing cefiderocol AST methodologies are imperative to ensure reliable susceptibility outcomes and optimized outcomes for patients with MDR infections.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337024","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":"Decrease in colistin resistance among young bovine and pig productions in France: relationship with colistin usage and stewardship measures.","authors":"Claire Chauvin, Eric Jouy, Anne Chevance, Corinne Jaureguy, Xavier Sauzea, Nathalie Jarrige, Géraldine Cazeau, Agnès Perrin-Guyomard, Magdéléna Chanteperdrix, Anne Hemonic, Alexandre Poissonnet, Delphine Urban","doi":"10.1093/jac/dkaf322","DOIUrl":"https://doi.org/10.1093/jac/dkaf322","url":null,"abstract":"<p><strong>Background: </strong>Colistin is a last-line antibiotic used to treat multiresistant human infections. The emergence of resistance in animal productions led to recommendations to reduce the veterinary use of colistin over the last decade. A long-term evaluation of policies on colistin usage is now deemed necessary.</p><p><strong>Objectives: </strong>This study aims to identify the stewardship measures regarding colistin usage in pig and bovine productions in France and characterize their long-term effects on colistin use and resistance.</p><p><strong>Methods: </strong>Measures contributing to colistin stewardship were inventoried from regulators, stakeholders and professionals. Data were collected from antimicrobial usage monitoring systems (i.e. national sales and on-farm usage) and two resistance surveillance programmes (one dedicated to clinical isolates and the other to commensal ones). Two time series-one of animal exposure to colistin and the other showing corresponding Escherichia coli resistance-and their relationships were analysed for the 2008-23 period.</p><p><strong>Results: </strong>Numerous different stewardship measures were progressively implemented in France during the study period. Colistin exposure significantly decreased in both bovine and pig productions, reaching a plateau in recent years. Colistin resistance concomitantly and markedly decreased, both time series being significantly associated.</p><p><strong>Conclusions: </strong>The long-term data available in France on colistin use and colistin resistance enabled analysis of the long-term impact of stewardship measures on the exposure of pigs and cattle, together with bacterial resistance to colistin. Both have significantly decreased towards a plateau, reflecting the effectiveness of the measures adopted to preserve colistin's usefulness in animal and human health.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312957","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":"The synergistic activity of tigecycline-based combinations against multidrug-resistant Acinetobacter baumannii-caused bloodstream infections.","authors":"Huan Zhang, Beibei Liang, Zhaoyi Tan, Rui Wang, Yun Cai","doi":"10.1093/jac/dkaf386","DOIUrl":"https://doi.org/10.1093/jac/dkaf386","url":null,"abstract":"<p><strong>Objectives: </strong>Bloodstream infections (BSIs) caused by MDR Acinetobacter baumannii (MDRAB) have become a serious threat. Tigecycline is one of the last-resort agents for MDRAB, but its monotherapy in BSIs is limited by insufficient serum exposure. Certain combination strategies can enhance anti-infection ability via a synergistic effect, thus achieving acceptable antimicrobial efficacy at a relatively lower concentration. Therefore, this study was conducted to explore tigecycline-based combinations with synergistic activity against MDRAB BSIs.</p><p><strong>Methods: </strong>Four clinically isolated MDRAB strains were investigated. The FIC index (FICI) of tigecycline in combination with clinical common antibiotics was assessed to screen synergistic combination strategies through chequerboard assays. The synergistic effect was then evaluated by an in vitro pharmacokinetics/pharmacodynamics (PK/PD) model through simulating human drug serum concentration-time profiles. Finally, a lethal BSI murine model was used to verify the synergistic efficacy of selected combination strategies in vivo.</p><p><strong>Results: </strong>Tigecycline combined with meropenem showed the strongest synergistic effect, with an FICI of ≤0.5 for all MDRAB strains, and was consequently selected for subsequent experiments. In the in vitro PK/PD model, high-dose tigecycline combined with meropenem showed excellent synergistic activity against tigecycline-susceptible but not against non-susceptible MDRAB strains. In a lethal BSI murine model induced by tigecycline-susceptible MDRAB, strong synergistic activity was verified in the high-dose tigecycline + meropenem group, with mortality reduced to zero and the bacterial load of blood, liver, lung and kidney significantly decreased (P < 0.05).</p><p><strong>Conclusions: </strong>High-dose tigecycline combined with meropenem displayed an excellent synergistic effect against BSIs caused by tigecycline-susceptible but not non-tigecycline-susceptible MDRAB, therefore providing a promising treatment choice for tigecycline-susceptible MDRAB BSIs in the clinic.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308077","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":"Dual β-lactam synergy in Enterococcus faecalis and its relationship with penicillin-ceftriaxone infective endocarditis treatment outcomes.","authors":"April Gregson, Shakeel Mowlaboccus, Sruthi Mamoottil Sudeep, Sophia Rizzo, Jignasa Purani, Elena Martinez, Geoffrey Coombs, Indy Sandaradura, Genevieve McKew","doi":"10.1093/jac/dkaf377","DOIUrl":"https://doi.org/10.1093/jac/dkaf377","url":null,"abstract":"<p><strong>Objectives: </strong>Benzylpenicillin with ceftriaxone is used for outpatient antimicrobial therapy of Enterococcus faecalis infective endocarditis (EFIE) due to poor stability of aminopenicillins. The aim was to correlate the impact of benzylpenicillin-ceftriaxone synergy on EFIE treated with benzylpenicillin-ceftriaxone, and investigate whether simpler phenotypic methods can predict synergy.</p><p><strong>Methods: </strong>Clinical outcomes of a retrospective cohort of EFIE patients were correlated with treatment and synergy. Isolates were assessed for synergy using the checkerboard method, compared with double disc diffusion (DDD) and layered and crossed gradient diffusion strip (GDS) tests, with sensitivity and specificity of these methods calculated.</p><p><strong>Results: </strong>Thirty-eight episodes of EFIE in 34 patients were included; the majority received benzylpenicillin-ceftriaxone alone (n = 16) or in sequence (n = 12; any benzylpenicillin-ceftriaxone n = 28), and 10 received other regimens. There was no statistical difference between any benzylpenicillin-ceftriaxone versus other therapies on outcomes, nor between benzylpenicillin-ceftriaxone synergy and outcome. GDS was an unreliable predictor of checkerboard synergy; DDD was reasonable. Five isolates lacked benzylpenicillin-ceftriaxone synergy (one also lacking ampicillin-ceftriaxone synergy); these all had high-level ceftriaxone resistance [zone diameter 6 mm, or broth microdilution (BMD) MIC >512 mg/L]. Most isolates from relapse cases developed reduced zone diameters to ceftriaxone. Two isolates lacking synergy had the same mutation near the ceftriaxone response regulator (CroR) binding site in the pbp4 promoter region.</p><p><strong>Conclusions: </strong>Ceftriaxone susceptibility, either MIC <512 mg/L by BMD or disc zone diameter >6 mm, is the best predictor of ampicillin-ceftriaxone and particularly benzylpenicillin-ceftriaxone synergy in E. faecalis. There was no clear relationship between the absence of benzylpenicillin-ceftriaxone synergy and outcome in this highly comorbid cohort.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308137","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}