International Journal of Antimicrobial Agents最新文献

{"title":"Long-acting lipoglycopeptides compared to standard-of-care for the treatment of complicated gram-positive infections: A systematic review and meta-analysis.","authors":"Dominick Salvatore, Jaci Moore, Taylor D Steuber","doi":"10.1016/j.ijantimicag.2025.107581","DOIUrl":"10.1016/j.ijantimicag.2025.107581","url":null,"abstract":"<p><strong>Objectives: </strong>Long-acting lipoglycopeptides (LA-LGPs) are being used more frequently for the treatment of complicated Gram-positive infections, including osteomyelitis, prosthetic joint infections, bloodstream infections, and endocarditis. This systematic review and meta-analysis compared the efficacy and safety of LA-LGP to the standard of care (SOC) antibiotics for the treatment of these infections.</p><p><strong>Methods: </strong>A systematic literature search was conducted using PubMed, Medline, Embase, Cochrane, and Clinicaltrials.gov through November 2024. Prospective and retrospective comparative studies evaluating patients being treated for complicated Gram-positive infections were included. Interventions included multi-dose LA-LGP, including dalbavancin and oritavancin, vs. SOC antibiotics. Risk of bias was assessed using Cochrane RoB 2 and ROBINS-I tools. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random effects model. The primary outcome was clinical success.</p><p><strong>Results: </strong>Fourteen studies (n = 1582 patients) were included. Studies included a wide array of indications and dosing schemes. LA-LGP was associated with significantly higher clinical success rates compared to SOC (RR = 1.14, 95% CI = 1.05-1.23, P < 0.01). No significant differences were observed for infection recurrence, mortality, adverse events (AEs), or serious adverse events (SAEs). LA-LGP was associated with fewer hospital readmissions. A subgroup analysis of bone and joint infections showed no significant difference in clinical success between LA-LGP and SOC.</p><p><strong>Conclusions: </strong>LA-LGP for the treatment of complicated Gram-positive infections resulted in similar efficacy and safety to SOC antibiotics and may be a reasonable alternative for such infections. Results should be interpreted with caution given the risk of bias and heterogeneity (PROSPERO Registration ID: CRD42024532465).</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107581"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717893","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":"Enhanced immunogenicity of SARS-CoV-2 antigen with aluminum adjuvant and polysaccharide nucleic acid fraction of Bacillus Calmette Guerin.","authors":"Jia Ji, Miaojin Zhu, Linwei Zhu, Zhiyong Liu, Shengmei Yang, Taoming Tang, Zhigang Wu, Danrong Shi, Jiale Zhang, Xiaodi Zhang, Hangping Yao","doi":"10.1016/j.ijantimicag.2025.107578","DOIUrl":"10.1016/j.ijantimicag.2025.107578","url":null,"abstract":"<p><p>Vaccine immunization strategies are crucial for eliciting vaccine-induced immune responses, particularly in immune compromised populations and older adults. In clinical practice in China, the polysaccharide nucleic acid fraction of Bacillus Calmette-Guérin (BCG-PSN) is extensively used as an immune modulatory agent. Herein, we describe a new immunization strategy using the SARS-CoV-2 antigen (original strain) with aluminum adjuvant and BCG-PSN. We evaluated whether BCG-PSN enhances humoral and cellular immune responses to the SARS-CoV-2 vaccine in K18-hACE2 and BALB/c mice by assessing antibody and germinal center (GC) responses, as well as the quantity and functionality of memory T cells in the spleen. At day 28 after the first immunization, the SARS-CoV-2 antigen with Alum, when combined with BCG-PSN, significantly elevated the levels of IgGantibodies. It significantly enhanced the spleen's GC structure, amplified the SARS-CoV-2 antigen-specific T cell response, and conferred protection to mice against the Delta variant challenge. This study provides a reference to evaluate immunization strategies for vaccines with high immunological efficacy, and the SARS-CoV-2 antigen combined with Alum and BCG-PSN enhances immunogenicity by significantly boosting cellular immune responses after vaccine administration. The study focuses on the impact of BCG-PSN on the SARS-CoV-2 antigen, examining its role in generating neutralizing antibodies (NAbs) and eliciting T cell responses.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107578"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707415","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":"Membrane-disrupting medium-chain fatty acids reduce Staphylococcus aureus persister cell survival during antibiotic treatment.","authors":"Yena Seo, Minjun Kim, Dae-Youn Kim, Ji-Won Park, Hyun Jung Kim, Kyun Heo, Tae-Jong Kim","doi":"10.1016/j.ijantimicag.2025.107648","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107648","url":null,"abstract":"<p><strong>Objectives: </strong>Eliminating persister cells is essential to improve treatment of chronic infections and to limit the emergence of resistant strains. Medium-chain fatty acids (MCFAs) are widely used in cosmetics and antibiotic ointments where Staphylococcus aureus is a common commensal. This study evaluated the potential of MCFAs to eradicate S. aureus persister cells and investigated their mechanisms of action.</p><p><strong>Methods: </strong>The bactericidal activity of MCFAs against S. aureus persisters was assessed after treatment with three antibiotics-ciprofloxacin, oxacillin, and tobramycin. Membrane permeability was analyzed by fluorescence microscopy and ATP leakage assays.</p><p><strong>Results: </strong>Octanoic, decanoic, and lauric acids at 10, 1, and 0.1 mM, respectively, significantly reduced antibiotic-surviving cells in persister-enriched populations, independent of antibiotic class. In contrast, myristic acid did not eliminate persisters up to 10 mM, although it was active against exponentially growing cells. The bactericidal activity of MCFAs increased with chain length from octanoic to lauric acid. Killing correlated with enhanced membrane permeability, whereas changes in membrane fluidity or transmembrane potential were not predictive.</p><p><strong>Conclusion: </strong>MCFAs, particularly lauric acid at low concentrations, effectively eradicate S. aureus persisters and may enhance skin health when incorporated into topical products. Their activity increases with chain length and is linked to membrane permeability disruption. Myristic acid, while effective against metabolically active cells, is ineffective against persisters, highlighting physiological differences between growth states.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107648"},"PeriodicalIF":4.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367917","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":"Fluconazole exposure during mechanical circulatory support (MCS) device insertion.","authors":"Kelly A Cairns, Kate Morton, Trisha N Peel, Iain J Abbott, David M Kaye, Silvana Marasco, Andrew A Udy, David Daly, Victoria Warner, Anna Coldham, Jeffrey D Pope, Hans G Schneider, Michael J Dooley","doi":"10.1016/j.ijantimicag.2025.107647","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107647","url":null,"abstract":"<p><strong>Background: </strong>Mechanical circulatory support (MCS) devices are an important intervention for patients with advanced heart failure. Invasive Candida spp. infections following MCS device insertion have been reported. The addition of fluconazole to surgical prophylaxis regimens is controversial and there is a lack of data describing exposures achieved during MCS device insertion.</p><p><strong>Methods: </strong>A pilot pharmacokinetic study was undertaken to determine the plasma fluconazole exposure achieved during MCS device insertion. Peri-operative fluconazole levels were drawn at four time points during the MCS device insertion surgery - knife-to-skin (KTS), start of cardiac bypass (SOB), cessation of cardiac bypass (EOB) and at time of skin closure (SC). A secondary outcome was to determine Candida spp. colonisation patterns in this patient cohort.</p><p><strong>Results: </strong>40 peri-operative plasma fluconazole concentrations (from 10 patients) were available for analysis. One patient received 400 mg IV fluconazole pre-operatively, the remainder 200 mg IV. The median measured concentration at KTS, SOB, EOB and SC was 3.85 mg/L (IQR: 3.53 to 4.48 mg/L), 3.75 mg/L (IQR: 3.45 to 4.23 mg/L), 3.45 mg/L (IQR: 3.08 to 3.75 mg/L) and 3.35 mg/L (IQR: 2.93 to 3.55 mg/L), respectively. Pre-operative Candida colonisation swabs isolated C. parapsilosis (n = 2), C. glabrata (n = 2) and C. albicans (n = 1). A single post-operative swab was positive with C. glabrata.</p><p><strong>Conclusion: </strong>In ten patients undergoing MCS device insertion, fluconazole 200 to 400 mg IV achieved median plasma levels of between 3 to 4 mg/L throughout the surgical procedure and may not adequately cover for C. glabrata.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107647"},"PeriodicalIF":4.6,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345074","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":"One Health: Virtual Special Issue in the International Journal of Antimicrobial Agents.","authors":"Reema Singh, Yonghong Xiao","doi":"10.1016/j.ijantimicag.2025.107645","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107645","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107645"},"PeriodicalIF":4.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336750","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 \"Human serum lipids affect Staphylococcus aureus sensitivity to phage infection\".","authors":"Nathkapach K Rattanapitoon, Nav La, Patpicha Arunsan, Schawanya K Rattanapitoon","doi":"10.1016/j.ijantimicag.2025.107644","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107644","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107644"},"PeriodicalIF":4.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307963","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":"Corrigendum to \"Disrupting bacterial metabolism by targeting LDH reverses Streptococcus suis aminoglycoside resistance\" [International Journal of Antimicrobial Agents 66/6 (2025) 1-16/107599].","authors":"Shuji Gao, Yingying Quan, Shenao Song, Wenjie Jin, Zhiheng Chang, Baobao Liu, Yuxin Wang, Li Yi, Yang Wang","doi":"10.1016/j.ijantimicag.2025.107631","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107631","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107631"},"PeriodicalIF":4.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274431","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 evaluation of a vancomycin dosing bundle in Paediatric Intensive Care.","authors":"Michael A Stokes, Tony Lai, Lana Reiter, Bradley Rockliff, Deirdre Hahn, Marino S Festa, Indy Sandaradura","doi":"10.1016/j.ijantimicag.2025.107638","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107638","url":null,"abstract":"<p><strong>Objective: </strong>To describe the impact of a real-world, vancomycin dosing bundle ('the bundle'), on vancomycin-associated nephrotoxicity (VAN) rates in critically ill children in a single paediatric intensive care unit.</p><p><strong>Methods: </strong>A retrospective observational study was conducted in an Australian tertiary paediatric intensive care unit (PICU) from January 2020 to December 2022. The study included all patients who received vancomycin for two or more doses with an associated vancomycin level. During the study period, a staggered implementation was undertaken entailing three interventions on vancomycin prescribing (the bundle): (i) employment of a pharmacist to the PICU, (ii) model informed personalised dosing (MIPD), and (iii) a reduction in initial vancomycin dosing (15 mg/kg six hourly, to 15 mg/kg for the first dose then 10 mg/kg six hourly thereafter) alongside a reduction in target trough concentrations from 10 - 20 mg/L to 7 - 15 mg/L,. Data on dosing, vancomycin concentrations, and patient characteristics were collected, and AUC₂₄ was calculated using MIPD software. VAN was defined as a creatinine increase of 0.5 mg/dL or 50% from baseline on two consecutive measurements. Statistical analysis explored associations between time and VAN outcomes.</p><p><strong>Results: </strong>A total of 648 vancomycin courses were analysed, across 477 unique patients, with a median treatment length of 44.59 hours. MIPD represented 18% of the total courses, increasing from 2% to 37% over the study period. VAN occurred in 11.3% of courses, with a consistent rate over the years (13% in 2020, 12% in 2021, and 9% in 2022). Severe VAN rates decreased from 8.6% in 2020 to 3.9% in 2022. The reduction in both severe (p = 0.16) and total (p = 0.4) VAN did not achieve statistical significance.</p><p><strong>Conclusions: </strong>Implementation of a staggered pharmacist-led vancomycin dosing bundle did not result in a statistically significant reduction in VAN rates over time. However, the observed reduction in severe VAN and associated reduction in AUC₂₄ warrants further investigation with a prospective study design in the high-risk PICU cohort.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107638"},"PeriodicalIF":4.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274525","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":"Molecular characterisation of two novel KPC variants mediating ceftazidime-avibactam resistance in ST11 Klebsiella pneumoniae.","authors":"Tengfei Guo, Li Ding, Siquan Shen, Chengkang Tang, Tao Jiang, Fupin Hu","doi":"10.1016/j.ijantimicag.2025.107642","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107642","url":null,"abstract":"<p><p>Mutations in bla_KPC that confer resistance to ceftazidime-avibactam in Klebsiella pneumoniae pose a new challenge in global clinical anti-infective therapy. Although reports on the mechanism of KPC variants have increased in recent years, there are still very few reports on the simultaneous development of two novel KPC variants in the same patient. In this study, we report two novel KPC variants, KPC-207 (L169Q and 274-275S ins) and KPC-208 (L169Q and D179Y), produced by a patient infected with KPC-producing ST11-KL19 K. pneumoniae which underwent a drug-resistant mutation during treatment. The mutation process encompassed a sequential transition from KPC-2 to KPC-207, then KPC-208, a reversion to KPC-207, and ultimately a return to KPC-208. Both KPC-207-and KPC-208-producing K. pneumoniae were resistant to ceftazidime-avibactam, but showed restored susceptibility to carbapenems. Cloning assay showed a 128- and 64-fold increase in the MIC of ceftazidime-avibactam for clonal strains carrying bla_KPC-207 and bla_KPC-208 compared to bla_KPC-2 carrier. Enzyme kinetic assays revealed diminished hydrolysis of imipenem and meropenem by KPC-207 and KPC-208, along with reduced inhibitory effect of avibactam on both proteins. Sequence analysis revealed that all clinical strains exhibited high homology and the core structure of the plasmid harboring the bla_KPC-207 and bla_KPC-208 genes was Tn1721-ISkpn6-bla_KPC-ISkpn27-IS26, which belonged to the A2-type Tn1721. Compared with the wild-type bla_KPC-2 gene, the bla_KPC-207 and bla_KPC-208 genes had essentially no effect on the cost of adaptation to K. pneumoniae. The antimicrobial susceptibility and the bla_KPC should be continuously monitored during clinical treatment of carbapenem-resistant K. pneumoniae with ceftazidime-avibactam.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107642"},"PeriodicalIF":4.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274435","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":"Expanded Applications of Omeprazole: Synergistic Reversal of Colistin Resistance in Acinetobacter baumannii.","authors":"Xiaowei Lv, Fan Ye, Juan Pan, Panjie Hu, Endian Sun, Hong Wen, Ziyue Zeng, Mengjie Wei, Jianzhong Ye, Tieli Zhou","doi":"10.1016/j.ijantimicag.2025.107639","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107639","url":null,"abstract":"<p><p>Acinetobacter baumannii (A. baumannii) is an opportunistic microorganism capable of triggering life-threatening infections. The rising prevalence of multidrug-resistant (MDR) A. baumannii in clinical settings has complicated treatment efforts. Colistin serves as the last-line therapy against multidrug-resistant A. baumannii. However, its resurgence has accelerated antimicrobial resistance. To address escalating resistance and stagnant drug development, repurposing clinical drugs for antibacterial applications shows significant promise. Omeprazole, a proton pump inhibitor, is widely used to treat digestive system disorders. This study demonstrated that the combination of omeprazole and colistin exhibits considerable antibacterial activity through checkerboard susceptibility assays, time-kill experiments, and live/dead bacterial cell viability tests. In vivo experiments using a mouse leg infection model confirmed the synergistic antibacterial effect. Further mechanistic investigations have disclosed that this combined medication exerts its antibacterial effect by inducing bacterial death through the accumulation of reactive oxygen species (ROS) and subsequent oxidative stress, by inhibiting the formation of biofilms, and by suppressing the expression of drug efflux pumps. Overall, this study discovered that the clinical drug omeprazole has the potential to act as an adjuvant to colistin, synergistically reversing colistin resistance in A. baumannii and providing a novel therapeutic strategy for the treatment of infections caused by this pathogen.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107639"},"PeriodicalIF":4.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274461","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}