International Journal of Antimicrobial Agents最新文献

{"title":"Effect of probiotic strain, duration, and dose on preventing ICU-acquired infection: A scoping review","authors":"Aqdar Mufareh Al-Aklabi ,&nbsp;Sara Muteb Alotaishan ,&nbsp;Yasmin Youssuf Al-Gindan ,&nbsp;Rabie Yousif Khattab","doi":"10.1016/j.ijantimicag.2026.107714","DOIUrl":"10.1016/j.ijantimicag.2026.107714","url":null,"abstract":"<div><h3>Background</h3><div>Intensive care unit-acquired infections (ICU-AIs) are prevalent among critically ill patients due to multiple invasive procedures. Probiotics have emerged as a potential preventive strategy to lower infection rates in ICU settings. However, studies assessing probiotic effectiveness have reported inconsistent results, suggesting that these discrepancies are due to variations in probiotic strain, intervention duration, and dosage. Despite the growing interest and the existence of several reviews, the optimal probiotic strain, duration, and dosage for ICU patients remain uncertain.</div></div><div><h3>Objectives</h3><div>This review aims to assess the impact of strain specificity, intervention duration, and dosage on the effectiveness of probiotic supplementation in preventing ICU-AIs.</div></div><div><h3>Methods</h3><div>This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A comprehensive search was conducted in electronic databases for English-language interventional and observational studies published between January 2014 and August 2024. Eligible studies were those that evaluated the efficacy of probiotics in reducing ICU-AIs. Data were extracted using a standardized form that included details on strain designation, intervention duration, and dosage. Findings were synthesized descriptively using narrative text, tables, and figures.</div></div><div><h3>Results</h3><div>Eighteen different probiotic strains were identified. <em>Lactobacillus acidophilus</em> LA-5, particularly in multi-strain formulations, was commonly associated with positive outcomes. Probiotic regimens with intervention durations of 14 days or more and dosages of at least 5 × 10⁹ CFU/day demonstrated greater effectiveness in reducing ICU-AIs.</div></div><div><h3>Conclusions</h3><div>Strain-specificity, intervention duration, and dosage are important factors influencing probiotic effectiveness in ICU-AI prevention. Further studies are needed to confirm the efficacy of promising strains and explore the potential of new ones.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 3","pages":"Article 107714"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951798","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":"Risk factors for bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii in ICU patients with any site colonisation: A prospective observational study","authors":"Giusy Tiseo ,&nbsp;Valentina Galfo ,&nbsp;Aurelio Lepore ,&nbsp;Manuela Pogliaghi ,&nbsp;Lorenzo Roberto Suardi ,&nbsp;Cesira Giordano ,&nbsp;Alessandro Leonildi ,&nbsp;Simona Barnini ,&nbsp;Marco Falcone","doi":"10.1016/j.ijantimicag.2026.107717","DOIUrl":"10.1016/j.ijantimicag.2026.107717","url":null,"abstract":"<div><h3>Objectives</h3><div>The aim of this study was to develop and validate a risk score to predict the occurrence of bloodstream infections (BSI) caused by carbapenem-resistant <em>Acinetobacter baumannii</em> (CRAB) among colonised intensive care unit (ICU) patients, in order to support early clinical decision-making and antimicrobial stewardship.</div></div><div><h3>Methods</h3><div>Prospective observational study including adult patients admitted to ICU with CRAB colonisation at any site at the University Hospital of Pisa, Italy (June 2020-June 2023). The primary outcome measure was BSI caused by CRAB. A multivariable regression analysis was performed to identify factors independently associated with CRAB-BSI. Regression coefficients were used to develop a risk score for CRAB-BSI. Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC-ROC).</div></div><div><h3>Results</h3><div>Among 283 colonised patients, 103/283 (36.4%) developed a BSI caused by CRAB. Median (IQR) time from colonisation to BSI was 4 days (1–8 days). On multivariable analysis, burns (OR: 8.219, 95% CI: 3.591–18.812, <em>P</em> &lt; 0.001), number of colonised sites (per-site: OR: 2.197, 95% CI: 1.363–3.541, <em>P</em> = 0.001), respiratory tract colonisation (OR: 4.285, 95% CI: 2.179–8.426, <em>P</em> &lt; 0.001), and cardiovascular disease (OR: 1.940, 95% CI: 1.068–3.524, <em>P</em> = 0.029) were independently associated with increased risk of BSI. The score ranged from 1 to 9 points. The AUC of the model was 0.817 (95% CI: 0.764–0.869, <em>P</em> &lt; 0.001). The negative predictive value (NPV) was 97.8% in patients without septic shock and 72.2% in those who developed septic shock.</div></div><div><h3>Conclusions</h3><div>The rate of CRAB-BSI among colonised patients is considerable. The proposed score may be useful, after external validation, for a rational empirical use of new antibiotics.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 3","pages":"Article 107717"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984749","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":"Resistance to sulbactam/durlobactam in carbapenem-resistant Acinetobacter baumannii in treatment-naive setting: In vitro data and genomic insights from Italian bloodstream isolates","authors":"Gabriele Bianco ,&nbsp;Gherard Batisti Biffignandi ,&nbsp;Matteo Boattini ,&nbsp;Sara Comini ,&nbsp;Cristina Costa ,&nbsp;Michela Vumbaca ,&nbsp;Paolo Gaibani","doi":"10.1016/j.ijantimicag.2026.107718","DOIUrl":"10.1016/j.ijantimicag.2026.107718","url":null,"abstract":"<div><h3>Objective</h3><div>This study evaluated the <em>in vitro</em> activity of sulbactam/durlobactam and comparators against carbapenem-resistant <em>Acinetobacter baumannii</em> (CRAB) bloodstream isolates from Italy and investigated genomic mechanisms underlying resistance.</div></div><div><h3>Methods</h3><div>A total of 110 consecutive CRAB isolates (2021–2023) were tested for susceptibility to sulbactam/durlobactam, cefiderocol, colistin, and comparators. Whole-genome sequencing (WGS) was performed on sulbactam/durlobactam-resistant isolates to characterise β-lactamase genes, outbreak dynamics, and mutations in penicillin-binding proteins (PBPs).</div></div><div><h3>Results</h3><div>Sulbactam/durlobactam inhibited 87.3% of isolates (MIC₅₀ = 2 mg/L; MIC₉₀ &gt; 64 mg/L), while 12.7% were resistant. Cefiderocol and colistin showed 91.8% and 96.4% susceptibility rates, respectively. All resistant isolates carried bla_OXA-23, and three also harbored <em>bla</em>_NDM-1. WGS revealed close clonal relationships (average nucleotide identity &gt; 99%) among <em>bla</em>_NDM-1 positive isolates (ST231) and among OXA-23-only isolates (ST837/ST369), indicating local outbreak dynamics. Comparative PBP analysis identified recurrent substitutions P112S and G137R (PBP1b), N392T and A515V (PBP3), and S329N (PBP5). Structural correlation suggests these mutations reduce β-lactam binding and may contribute to resistance, particularly when combined with NDM-1.</div></div><div><h3>Conclusions</h3><div>This study provides early evidence of sulbactam/durlobactam resistance in treatment-naïve CRAB from Italy, driven by NDM-1 co-production and PBP alterations. The coexistence of epidemic ST231 and ST837/ST369 clones highlights the need for continuous genomic surveillance and prudent antibiotic stewardship to prevent dissemination of resistant <em>A. baumannii</em> lineages.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 3","pages":"Article 107718"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998059","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-world daptomycin use with a focus on muscle toxicity: A multicentric retrospective study","authors":"C. Airaud ,&nbsp;E. Demay ,&nbsp;V. Dias Meireles ,&nbsp;David Luque Paz ,&nbsp;Pierre Tattevin ,&nbsp;P. Lazaro ,&nbsp;M. Lahouati ,&nbsp;A. Bacle","doi":"10.1016/j.ijantimicag.2026.107721","DOIUrl":"10.1016/j.ijantimicag.2026.107721","url":null,"abstract":"<div><h3>Background</h3><div>Daptomycin is increasingly used to treat Gram-positive infections, but carries a risk of muscle toxicity. Despite guideline recommendations, real-world adherence to safety monitoring remains poorly documented.</div></div><div><h3>Objectives</h3><div>To evaluate daptomycin prescribing practices and identify risk factors for muscle toxicity across three French university hospitals.</div></div><div><h3>Methods</h3><div>We conducted a retrospective multicenter study of adults (≥18 y) treated with daptomycin between June 2021 and May 2022. Data included demographics, treatment, monitoring, microbiology, and adverse events. Muscle toxicity was defined as an elevation of creatine kinase (CK) (&gt;5 upper normal value) and/or rhabdomyolysis, identified by explicit documentation in medical records. Logistic regression identified associated factors.</div></div><div><h3>Results</h3><div>We collected data from 1407 patients (65.1% male; mean age 62.4 ± 16.5) treated with daptomycin during the study period, for a mean duration of 7.87 ± 7.05 d. Most patients (93.9%) received high-dose daptomycin, ≥8 mg/kg/d. Combination therapy was frequent (72%), mostly with β-lactams (91.8%). CK monitoring was reported in 34.2% of patients, muscle toxicity was reported in 4.9%, including rhabdomyolysis in 2.7%. Statins were co-prescribed without discontinuation in 15.6% of cases. In multivariate analysis, concomitant use of high-risk comedications, including statins and fibrates (OR [95% CI] = 6.68 [3.28–13.97], <em>P</em> &lt; 0.001) and obesity (OR 2.25 [1.07–4.72], <em>P</em> = 0.03) were independently associated with muscle toxicity.</div></div><div><h3>Conclusion</h3><div>Despite widespread use of high-dose daptomycin, safety monitoring was inconsistent. Systematic CK testing and careful review of myotoxic co-medications are essential to mitigate adverse events in clinical practice.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 3","pages":"Article 107721"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043780","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":"International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page","authors":"","doi":"10.1016/j.ijantimicag.2026.107746","DOIUrl":"10.1016/j.ijantimicag.2026.107746","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 3","pages":"Article 107746"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147400733","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":"Title Page & Editorial Board","authors":"","doi":"10.1016/S0924-8579(26)00042-7","DOIUrl":"10.1016/S0924-8579(26)00042-7","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 3","pages":"Article 107753"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147400735","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":"Pharmacokinetics of ampicillin, sulbactam and combined ampicillin/sulbactam in subcutis, muscle and plasma: A microdialysis trial in healthy volunteers","authors":"Anselm Jorda ,&nbsp;Lena Pracher ,&nbsp;Marlene Prager ,&nbsp;Felix Bergmann ,&nbsp;Amelie Leutzendorff ,&nbsp;Theresa Pecho ,&nbsp;Maria Sanz-Codina ,&nbsp;Lukas Schulz ,&nbsp;Edith Lackner ,&nbsp;Christoph Dorn ,&nbsp;Markus Zeitlinger ,&nbsp;Valentin al Jalali","doi":"10.1016/j.ijantimicag.2026.107716","DOIUrl":"10.1016/j.ijantimicag.2026.107716","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to investigate pharmacokinetic (PK)/pharmacodynamic (PD) target attainment, tissue and plasma PK and PK interactions of ampicillin/sulbactam.</div></div><div><h3>Methods</h3><div>Thirty healthy volunteers received a single intravenous 30-min infusion of ampicillin 2000 mg (<em>n</em> = 10), sulbactam 1000 mg (<em>n</em> = 10) or ampicillin 2000 mg/sulbactam 1000 mg (<em>n</em> = 10). Drug concentrations were determined in the interstitial fluid of subcutis and muscle using microdialysis and in plasma over 8 h. A non-compartmental analysis and an adjustment to the plasma protein binding determined by ultrafiltration were performed to calculate PK parameters and the proportion of participants achieving PK/PD targets. The PK/PD targets selected for ampicillin were <em>f</em>T_&gt;MIC &gt;50% and <em>f</em>T_&gt;MIC &gt;70%, reflecting established efficacy thresholds for β-lactam antibiotics across varying degrees of disease severity.</div></div><div><h3>Results</h3><div>Fewer than 90% of participants reached the PK/PD target of ampicillin <em>f</em>T_&gt;MIC &gt; 50% at MICs ≥4 mg/L and the target of <em>f</em>T_&gt;MIC &gt; 70% at MICs ≥0.5 mg/L in plasma, muscle and subcutis, assuming three times daily dosing. In the pooled analysis, the mean <em>f</em>AUC_0-8 of ampicillin was 80 (S.D. 25), 84 (S.D. 29) and 80 (S.D. 20) mg/L × h in subcutis, muscle and plasma. The mean <em>f</em>AUC_0-8 of sulbactam was 49 (S.D. 13), 54 (S.D. 15) and 60 (S.D. 17) mg/L × h in subcutis, muscle and plasma. While ampicillin concentrations were similar between the groups, sulbactam showed higher concentrations in the combined group than in the sulbactam alone group, including an increased plasma <em>f</em>AUC_0-8 (68 [S.D. 12] vs. 51 [S.D. 18] mg/L × h, <em>P</em> = 0.027).</div></div><div><h3>Conclusion</h3><div>Although tissue concentrations almost reached plasma levels, the target attainment of ampicillin may be suboptimal when administered three times daily. Sulbactam tissue and plasma levels were slightly higher after combined administration with ampicillin than after administration of sulbactam alone.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 3","pages":"Article 107716"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948743","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":"Pharmacokinetics and pharmacodynamics of bacteriophage therapy: A scoping review","authors":"Andrew T Nguyen ,&nbsp;Nicita Mehta ,&nbsp;KaiLan Mackey ,&nbsp;Thomas Cummiskey ,&nbsp;Edward K. Rodriguez ,&nbsp;Jason Young","doi":"10.1016/j.ijantimicag.2025.107705","DOIUrl":"10.1016/j.ijantimicag.2025.107705","url":null,"abstract":"<div><h3>Objectives</h3><div>The interest in bacteriophage therapy has significantly increased due to the rising prevalence of antibiotic-resistant bacterial infections. However, the pharmacology of bacteriophage therapy has not been systematically reviewed. This scoping review aims to summarize the current state of bacteriophage pharmacokinetics and pharmacodynamics research to identify knowledge gaps and guide future research.</div></div><div><h3>Methods</h3><div>Following PRISMA-ScR guidelines, we conducted a scoping review through December 18th, 2023 of MEDLINE (Ovid), PubMed, Embase (Elsevier), Web of Science Core Collection (Clarivate), and Cochrane Central. We included studies that presented original data on the pharmacokinetics and pharmacodynamics of bacteriophage therapy for in vivo infection treatment.</div></div><div><h3>Results</h3><div>In total, 34 in vivo studies were identified varying in multiple dimensions, including model organisms, target bacteria, delivery vehicles, modes of administration, and phage type. The scoping review maps the current research landscape of in vivo bacteriophage pharmacology.</div></div><div><h3>Conclusions</h3><div>Bacteriophage therapy shows notable promise as a potential alternative or therapeutic adjunct to antibiotics in clinical disease settings. Several studies of phage pharmacokinetics and pharmacodynamics have been conducted; however, these studies differ in multiple dimensions, complicating attempts to develop general principles for standardized phage administration. Further, significant gaps remain in understanding the numerous intrinsic phage and host factors that might affect the pharmacokinetics and pharmacodynamics of phage therapy in vivo.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 3","pages":"Article 107705"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145943514","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":"Beneficial effects of a compound probiotic in Helicobacter pylori-infected patients aged over 40 years: An open-label randomised clinical trial","authors":"Chenghai Yang ,&nbsp;Jie Cheng ,&nbsp;Meng Zhang ,&nbsp;Bingyun Lu ,&nbsp;Lele Wu ,&nbsp;Hui Qiao ,&nbsp;Xiaohui Zhao ,&nbsp;Heping Zhang ,&nbsp;Wenyi Zhang ,&nbsp;Ye Chen","doi":"10.1016/j.ijantimicag.2026.107712","DOIUrl":"10.1016/j.ijantimicag.2026.107712","url":null,"abstract":"<div><h3>Background</h3><div>Bismuth quadruple therapy (BQT) is a recommended first-line regimen for <em>Helicobacter pylori</em> (<em>H. pylori)</em> eradication., but its use is limited by side effects and restricted bismuth availability. Probiotic represents an investigational alternative strategy. This study compared the efficacy and safety of triple therapy plus probiotics (TTP)with BQT.</div></div><div><h3>Methods</h3><div>Patients with <em>H. pylori</em> infection were randomised to receive either TTP (probiotics, amoxicillin, clarithromycin and esomeprazole) or BQT (bismuth potassium citrate, amoxicillin, clarithromycin and esomeprazole) for 14 d. The primary endpoint was the eradication rate by ¹³C-urea breath test ≥28 d after treatment completion. Secondary endpoints included adverse events and adherence.</div></div><div><h3>Results</h3><div>The eradication rates for TTP vs. BQT were 76.4% (126/165) and 86.6% (142/164) in the intention-to-treat (ITT) analysis (difference, −10.2%; 95% CI: −18.5% to −1.9%; <em>P</em> = 0.521) and 84.0% (126/150) and 94.7% (142/150) in the protocol (PP) analysis (difference, −10.7%; 95% CI: −17.5% to −3.8%, <em>P</em> = 0.576). Among patients aged ≥40 y, eradication rates were comparable between TTP and BQT in both the ITT and PP analysis (91.9% vs. 84.9% and 97.1% vs. 93.8%, <em>P</em> = 0.015 and <em>P</em> = 0.019 for noninferiority, respectively). The incidence of adverse event was lower in the TTP group (17.8% vs. 28.7%; <em>P</em> = 0.029). Furthermore, TTP preserved gut microbiota stability, whereas BQT induced dysbiosis.</div></div><div><h3>Conclusion</h3><div>While TTP was inferior to BQT in eradication efficacy, it demonstrated better tolerability and protective effects against gut microbiota dysbiosis. In patients aged ≥40 y, TTP achieved non-inferior eradication rates, suggesting this subgroup may warrant further investigation.</div><div>Trial registration number: ChiCTR2200058491</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 3","pages":"Article 107712"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951813","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":"Effect of ibuprofen on the pharmacokinetics of intravenous flucloxacillin in healthy adults","authors":"Alison Boast ,&nbsp;Amy Legg ,&nbsp;James McCarthy ,&nbsp;Jason A Roberts ,&nbsp;Stephen YC Tong ,&nbsp;Stephen Duffull ,&nbsp;Amanda Gwee","doi":"10.1016/j.ijantimicag.2025.107684","DOIUrl":"10.1016/j.ijantimicag.2025.107684","url":null,"abstract":"<div><h3>Objective</h3><div>Ibuprofen is frequently co-administered with antibiotics for its analgesic effect when treating infections. In vitro studies have shown that ibuprofen exhibits concentration-dependent inhibition of organic anion transporters (OAT) 1 and OAT3, and therefore may reduce clearance of β-lactams, including flucloxacillin, in a similar manner to probenecid. We therefore aimed to evaluate the effect of ibuprofen on the pharmacokinetics (PK) of flucloxacillin in healthy volunteers.</div></div><div><h3>Methods</h3><div>A single-site PK study of 10 healthy adult volunteers was carried out. Over a 3-d intervention period, participants received intravenous (IV) flucloxacillin 2000 mg twice daily with oral ibuprofen 400 mg twice daily on days 2 and 3. Total and unbound flucloxacillin plasma concentrations were collected at predefined time points. A population PK model was developed using a non-linear mixed-effects modelling approach, and ibuprofen was assessed as a covariate in the final model.</div></div><div><h3>Results</h3><div>Ten participants with a median age of 24.4 y (range 18.8–54.5 y) and median weight of 68.3 kg (range 50.5–85.7 kg) were included. A median of 51.5 (range 34–52) samples was collected per participant. The final two-compartment model included saturable protein binding and allometric scaling of weight on clearance. Ibuprofen was not found to be a significant covariate on K_d (binding dissociation constant), B_max (maximum binding capacity), or clearance.</div></div><div><h3>Conclusion</h3><div>Orally administered ibuprofen had no measurable effect on plasma flucloxacillin PK in healthy adults. Given the lack of drug–drug interaction, there is no benefit to prescribing ibuprofen alongside flucloxacillin to increase flucloxacillin exposure.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107684"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668231","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}