JAC-Antimicrobial Resistance最新文献

{"title":"<i>In vivo</i> pharmacokinetics, therapeutic efficacy and immune response of bacteriophage vB_AbaSt_W16 against carbapenem-resistant <i>Acinetobacter baumannii</i>.","authors":"Yoon-Jung Choi, Md Shamsuzzaman, Jae-Eon Lee, Yong Hyun Jeon, Hyungjin Kim, Young-Ran Yoon, Md Shohel Rana, Joohun Shin, Shukho Kim, Jungmin Kim","doi":"10.1093/jacamr/dlaf121","DOIUrl":"https://doi.org/10.1093/jacamr/dlaf121","url":null,"abstract":"<p><strong>Background: </strong>The increasing prevalence of carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) infections necessitates alternative therapeutic strategies. Bacteriophage therapy has emerged as a promising approach, yet its clinical implementation is hindered by limited pharmacokinetic (PK) and pharmacodynamic (PD) data.</p><p><strong>Methods: </strong>The PK and PD properties of <i>Acinetobacter</i> phage vB_AbaSt_W16 were evaluated in a murine model. Systemic distribution, clearance kinetics and efficacy were assessed following oral (PO) and intraperitoneal (IP) administration. Conventional PK/PD analysis and real-time fluorescence imaging were used to examine <i>in vivo</i> phage dynamics.</p><p><strong>Results: </strong>After administration, vB_AbaSt_W16 rapidly disseminated systemically within 1 h, reaching peak concentrations at 8 h. Most tissues cleared the phage within 72 h, though residual amounts persisted in the spleen for up to 92 h. In a murine infection model, vB_AbaSt_W16 demonstrated potent antibacterial activity, reducing CRAB bacterial loads by 4-7 log₁₀ cfu/mL within 24 h. Compared with PO administration, IP administration resulted in higher systemic bioavailability and bacterial clearance. Fluorescence imaging enabled non-invasive, real-time monitoring of phage distribution, demonstrating its utility as a PK assessment tool. Notably, phage treatment did not trigger significant pro-inflammatory cytokine release (TNF-α, IL-6) in healthy mice and effectively reduced CRAB-induced inflammation.</p><p><strong>Conclusions: </strong>These findings highlight the therapeutic potential of vB_AbaSt_W16 and provide critical insights into its PK behaviour. The results support further clinical development of this phage for CRAB infections.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf121"},"PeriodicalIF":3.3,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly genetically diverse variants of hepatitis C virus still predominate in Cameroon but with low frequency of mutations associated to resistance of NS5B polymerase-targeted antivirals.","authors":"Fabrice Levoa Eteme, Nadege Mafopa Goumkwa, Alliance-Laure Otam, Cindy Lobe, Clauvis Kunkeng Yengo, Mathurin Kowo, Laure Tchapda, Inoussa Pempeme, Williams Anderson Ngameleu, Junior Ekunidi Engarimbi, Signang Alberic Ndonku, Diapa Nana Yannick, Patrick Lebon Awoumou, Marie-Ange Kwizera, Njoya Oudou, Marie Claire Assoumou Okomo, Charles Ntungwen Fokunang, Henry Namme Luma, Judith Ndongo Embola Torimiro","doi":"10.1093/jacamr/dlaf114","DOIUrl":"https://doi.org/10.1093/jacamr/dlaf114","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis C is of low endemicity (<2%) in the general population in Cameroon, with genotypes (GTs) 1, 2 and 4 reported frequently identified. In 2016, direct-acting antiviral agents (DAAs) were included in the Treatment Guidelines for hepatitis C in Cameroon. The aim of this study was to investigate hepatitis C virus (HCV) variability and frequency of NS5B naturally occurring polymorphisms and transmitted resistance-associated mutations or substitutions (RAMs or RASs) in DAAs-naïve patients.</p><p><strong>Methods: </strong>From 240 HCV-infected, DAA-naïve individuals, the NS5B region of 92 samples were sequenced, genotyped by phylogeny using MEGA 11.0.13 software and analysed for polymorphisms conferring resistance to polymerase inhibitors using bioinformatics tools (Geno2Pheno HCV 0.92 and BioEdit version 7.2.5).</p><p><strong>Results: </strong>Thirty-two GT1 (34.8%), 37 GT2 (40.2%), 22 GT4 (23.9%) and 1 GT5 (1.1%), 13 subtypes (1e, 1g, 1h, 1j, 1l, 2j, 2r, 4a, 4f, 4l, 4p, 4t and 5a) were found. Thirty-four GT2 sequences clustered together without any reference sequences and therefore could not be subtyped. The NS5B S282T resistance-associated substitutions was not detected in any sample. However, the polymorphisms of unreported resistance-associated impact in positions 316 and 321 were identified: C316H (8.7%), C316N (18.5%), V321I (6.5%) and a double mutant C316H/V321I (4.3%). Comparison of GTs obtained by a commercial PCR kit versus Sanger sequencing and phylogeny of the NS5B region, showed a discrepancy of 30%.</p><p><strong>Conclusion: </strong>Genotype 5 was identified for the first time in Cameroon. The frequency of V321I and C316H/N polymorphism with unknown impact on NS5B polymerase inhibitors is increasing in Cameroon.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf114"},"PeriodicalIF":3.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In vitro</i> antimicrobial susceptibility of <i>Mycoplasma pneumoniae</i> isolates across different regions of China in 2023.","authors":"Chao Yan, Yujie Chen, Xue Ren, Xinyu Jia, Bing Du, Hanqing Zhao, Yanling Feng, Guanhua Xue, Jinghua Cui, Xuanfeng Liu, Jing Yuan","doi":"10.1093/jacamr/dlaf124","DOIUrl":"https://doi.org/10.1093/jacamr/dlaf124","url":null,"abstract":"<p><strong>Objectives: </strong>To analyse the <i>in vitro</i> antimicrobial susceptibility of <i>Mycoplasma pneumoniae</i> (<i>M. pneumoniae</i>) isolates from 10 different provinces/municipalities across China during the 2023 epidemic.</p><p><strong>Methods: </strong>We collected respiratory specimens from paediatric patients diagnosed with <i>M. pneumoniae</i> pneumonia from 10 different provinces/municipalities including Beijing, Shanghai, Liaoning, Gansu, Shanxi, Henan, Hunan, Jiangsu, Guangxi and Guangdong across China from October to December 2023. <i>M. pneumoniae</i> was isolated and cultured from these specimens. Macrolide resistance-associated mutations A2063G or A2064G in the 23S rRNA gene were detected. Minimum inhibitory concentrations (MICs) of five antibiotics (erythromycin, azithromycin, tetracycline, moxifloxacin and doxycycline) were determined using PPLO broth and microdilution susceptibility tests.</p><p><strong>Results: </strong>A total of 190 <i>M. pneumoniae</i> isolates were analysed. All isolates harboured the A2063G mutation. All isolates (100%) were highly resistant to erythromycin (MIC range: 128-1024 mg/L) and azithromycin (MIC range: 4-256 mg/L), but susceptible to tetracycline (MIC range: ≤0.125-1 mg/L), doxycycline (MIC range: ≤0.125-1 mg/L) and moxifloxacin (MIC range: ≤0.125 mg/L). For azithromycin and tetracycline, <i>M. pneumoniae</i> isolates from different regions of China showed different susceptibilities. The MICs of tetracycline against <i>M. pneumoniae</i> from northern China were significantly lower than those from central China and southern China. Comparisons among provinces/municipalities suggested that isolates from Hunan and Beijing were more resistant to azithromycin. For tetracycline, the MICs were significantly lower among isolates from Beijing.</p><p><strong>Conclusions: </strong>During the 2023 epidemic, isolates of <i>M. pneumoniae</i> were highly resistant to macrolides but remained susceptible to tetracycline and quinolones. For the treatment of macrolide-resistant <i>M. pneumoniae</i>, tetracycline, moxifloxacin and doxycycline would be the recommended antibiotics based on our findings.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf124"},"PeriodicalIF":3.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The global epidemiology of carbapenem-resistant <i>Acinetobacter baumannii</i>.","authors":"Angelique Boutzoukas, Yohei Doi","doi":"10.1093/jacamr/dlaf134","DOIUrl":"10.1093/jacamr/dlaf134","url":null,"abstract":"<p><p>Carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAb) is a challenging, environmentally hardy organism with a propensity to spread within hospitals and a predilection to infect critically ill, vulnerable patients. With its potential for rapid transmission, limited treatment options, and substantial mortality, CRAb is recognized as a critical, top-priority pathogen. Since its initial discovery in 1985, CRAb has disseminated globally, presenting a significant public health threat. CRAb is now endemic in many regions in Europe, South America, Asia, and Africa and globally contributes to over 50 000 deaths each year. Its ability to adhere to hospital surfaces, withstand desiccation, and form biofilms leads to widespread outbreaks. At-risk populations include those hospitalized and ventilated, and the most frequent presentations are respiratory and bloodstream infections. Carbapenem resistance in CRAb is primarily mediated by plasmid-borne carbapenemase genes, especially <i>bla</i> _OXA-23. These genes, carried by several epidemic international clones, including IC1 and IC2, have facilitated the global dissemination of CRAb through horizontal gene transfer in healthcare settings. Mortality rates are >20% and vary substantially by region and by type of infection, with bloodstream infections carrying >40% mortality. Despite its significant impact, the development of treatments for CRAb remains inadequate. The novel agent sulbactam-durlobactam holds promise for improved patient outcomes, but ongoing therapeutic development, infection prevention, and antimicrobial stewardship are critical to combat this formidable pathogen. Here, we review the emergence and dissemination of CRAb, its molecular epidemiology and resistance mechanisms, summarize contemporary global clinical epidemiology and patient outcomes, and briefly describe existing and future therapeutics.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf134"},"PeriodicalIF":3.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in antibiotic dispensing for children in Belgian ambulatory care: time series analysis before, during, and after the COVID-19 pandemic.","authors":"Hannelore Dillen, Axelle Van de Velde, Chloë Withofs, Laure Wynants, Jan Y Verbakel","doi":"10.1093/jacamr/dlaf135","DOIUrl":"10.1093/jacamr/dlaf135","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study is to analyse trends in paediatric antibiotic use in Belgian ambulatory care across three COVID-19 pandemic-related periods.</p><p><strong>Methods: </strong>We conducted a retrospective time series analysis using autoregressive integrated moving average modelling. The analysis is based on anonymized pharmacy dispensing data for antibiotics delivered to Belgian children aged 0-12 years, retrieved from Farmanet for the period from 2014 until 2023. The outcome measures were the number of packages, expenditures and DDDs. Outcomes were analysed for all antibiotics collectively and for subgroups based on patient characteristics, prescriber specialty, geographic region and antibiotic characteristics.</p><p><strong>Results: </strong>Antibiotic use among children in Belgian ambulatory care sharply declined during the COVID-19 pandemic (-42.7%), followed by a gradual return to pre-pandemic levels (+66.9%), which was primarily driven by prescriptions of antibiotics commonly used for respiratory tract infections. The initial reduction exceeded expected seasonal variations. The largest decreases during the pandemic and subsequent increases were observed among children aged 7-12 years, those with standard reimbursement, in prescriptions by general practitioners and in rural areas of Flanders and the Walloon region.</p><p><strong>Conclusions: </strong>The COVID-19 pandemic significantly disrupted paediatric antibiotic prescribing patterns in Belgian ambulatory care. These findings highlight the importance of sustained antimicrobial stewardship efforts, not only in routine healthcare settings but also during periods of altered care delivery.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf135"},"PeriodicalIF":3.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aztreonam-avibactam for the treatment of serious infections caused by metallo-β-lactamase-producing Gram-negative pathogens: a Phase 3 randomized trial (ASSEMBLE).","authors":"George L Daikos, José Miguel Cisneros, Yehuda Carmeli, Minggui Wang, Chee Loon Leong, Konstantinos Pontikis, Anastasia Anderzhanova, Simin Florescu, Roman Kozlov, Eduardo Rodriguez-Noriega, Mina Psichogiou, Pinyo Rattanaumpawan, Anca Streinu-Cercel, Venkatasubramanian Ramasubramanian, Francis F Arhin, Halley Rogers, Michele Wible, Joanne Leaney, Daria Jacobson, Rienk Pypstra, Joseph W Chow","doi":"10.1093/jacamr/dlaf131","DOIUrl":"10.1093/jacamr/dlaf131","url":null,"abstract":"<p><strong>Background: </strong>The Phase 3 ASSEMBLE study investigated aztreonam-avibactam versus best available therapy (BAT) for treatment of complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI), hospital-acquired/ventilator-associated pneumonia (HAP/VAP) or bloodstream infection (BSI) caused by confirmed MBL-producing multidrug-resistant pathogens.</p><p><strong>Methods: </strong>This prospective, multicentre, randomized, open-label, central assessor-blinded study randomized hospitalized adults 2:1 to aztreonam-avibactam [+ metronidazole (cIAI)] or BAT for 5-14 (cIAI, cUTI and BSI) or 7-14 (HAP/VAP) days. Primary endpoint was clinical cure at test-of-cure (TOC) visit on Day 28  ±  3 [microbiological ITT (micro-ITT) analysis set]. Secondary endpoints included microbiological response at TOC, 28-day mortality and safety. No formal hypothesis testing was planned.</p><p><strong>Results: </strong>Fifteen patients were randomized [aztreonam-avibactam, <i>n</i> = 12; BAT, <i>n</i> = 3 (ITT and micro-ITT analysis sets)]. Most frequent baseline pathogens were Enterobacterales; <i>Klebsiella pneumoniae</i> was most common [aztreonam-avibactam, 6/12 (50%); BAT, 2/3 (67%)]. MBL subtypes/variants identified in the aztreonam-avibactam group were NDM-1 (<i>n</i> = 7), NDM-5 (<i>n</i> = 3), VIM-2 (<i>n</i> = 2) and L1 (<i>n</i> = 3); and for BAT were NDM-1 (<i>n</i> = 2) and NDM-5 (<i>n</i> = 1). Clinical cure rates at TOC were 5/12 (42%) for aztreonam-avibactam and 0/3 (0%) for BAT. Per-patient microbiological responses were generally consistent with clinical responses. Twenty-eight-day all-cause mortality rates for aztreonam-avibactam and BAT were 1/12 (8%) and 1/3 (33%), respectively. Aztreonam-avibactam was generally well-tolerated, with no treatment-related serious adverse events.</p><p><strong>Conclusions: </strong>These Phase 3 data provide support for aztreonam-avibactam as a potential therapeutic option for difficult-to-treat infections caused by MBL-producing Gram-negative bacteria.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf131"},"PeriodicalIF":3.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Factors associated with blood culture sampling for adult acute care hospital patients with suspected severe infection: a scoping review using a socioecological framework.","authors":"","doi":"10.1093/jacamr/dlaf133","DOIUrl":"10.1093/jacamr/dlaf133","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/jacamr/dlaf043.].</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf133"},"PeriodicalIF":3.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of a rapid identification panel for fungemia.","authors":"Emily A Siegrist, Bryan P White, Denise Robison, Cindy McCloskey, Maria Alkozah, Nelson Agudelo Higuita, Rita Wilson Dib, Joseph Sassine","doi":"10.1093/jacamr/dlaf110","DOIUrl":"10.1093/jacamr/dlaf110","url":null,"abstract":"<p><p>Bloodstream infections due to yeast are associated with a high mortality rate. There is a lack of data that evaluate the real-world sensitivity of a rapid detection system for bloodstream infections due to yeast or the impact of these results on antimicrobial stewardship. The aim of this study was to evaluate the sensitivity of an ePlex panel (BCID-FP) for rapid detection of yeast from a positive blood culture bottle and to evaluate the impact of these rapid results on antifungal escalation or de-escalation. We evaluated 63 episodes of fungemia and found a sensitivity of 94%, lower than the 99%-100% stated in the package insert. Most common pathogens were <i>Candida glabrata</i> (36%), <i>Candida albicans</i> (24%), <i>Candida parapsilosis</i> (10%) and <i>Candida krusei</i> (10%). Only 57.1% of BCID-FP results lead to a change in antifungal therapy, most of which was initiation of an echinocandin. The real-world sensitivity of the BCID-FP panel was lower than anticipated and rarely led to de-escalation of antifungal therapy.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf110"},"PeriodicalIF":3.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid valve sterilization with meropenem plus ceftolozane/tazobactam combination therapy for <i>Pseudomonas aeruginosa</i> prosthetic valve endocarditis.","authors":"Valliammai Alaguvel, Anuj K Khetarpal, Allen Jankeel, Wendy A Tapia-Cano, Gabriela Martinez, Arianna Lorenzana, Zoe Hsiao, Warren Rose, George Sakoulas, Erlinda R Ulloa","doi":"10.1093/jacamr/dlaf112","DOIUrl":"10.1093/jacamr/dlaf112","url":null,"abstract":"<p><strong>Background: </strong><i>Pseudomonas aeruginosa</i> infective endocarditis (IE) presents a significant clinical challenge, leading to high rates of treatment failure and mortality. Even with the use of antipseudomonal β-lactams combined with aminoglycosides or fluoroquinolones, these therapies often fail to provide clinical resolution and are frequently accompanied by severe adverse effects.</p><p><strong>Methods: </strong>We report a case of <i>P. aeruginosa</i> prosthetic valve endocarditis successfully treated with a combination of meropenem and ceftolozane/tazobactam. To investigate the synergistic effects of this combination, we conducted checkerboard, time-kill, human whole blood killing, and biofilm assays, as well as a simulated endocardial vegetation (SEV) model.</p><p><strong>Results: </strong>Meropenem plus ceftolozane/tazobactam combination therapy successfully bridged the patient to cardiac surgery, achieving rapid microbiological clearance and sterile intraoperative valve cultures. While checkerboard assays showed additivity, time-kill assays with subtherapeutic antibiotic concentrations did not demonstrate synergy in standard media. However, significant synergy was observed in human whole blood and biofilm environments, with modestly improved activity in the SEV model.</p><p><strong>Conclusions: </strong>The combination of meropenem and ceftolozane/tazobactam demonstrates promising synergy in physiologically relevant conditions, offering a potentially safer alternative for treating <i>P. aeruginosa</i> IE and stabilizing complex patients prior to cardiac surgery. Further clinical investigation is needed to evaluate its efficacy and safety profile in severe <i>Pseudomonas</i> infections, including IE.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf112"},"PeriodicalIF":3.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the mechanisms of resistance to azole antifungals in <i>Candida</i> species.","authors":"Yunxiao Li, Charlotte Hind, Jessica Furner-Pardoe, J Mark Sutton, Khondaker Miraz Rahman","doi":"10.1093/jacamr/dlaf106","DOIUrl":"10.1093/jacamr/dlaf106","url":null,"abstract":"<p><p>Cases of <i>Candida</i> infection have been on the rise in recent years. A comprehensive and clear understanding of the mechanisms of antifungal resistance is fundamental for developing novel therapies to address the current and emerging threat of fungal diseases. Certain <i>Candida</i> species can cause superficial or invasive infections in immunocompromised hosts, and invasive <i>Candida</i> infections are major contributors to infectious disease deaths. As fungi are eukaryotes like humans, there are only a limited number of unique molecular targets available for antifungal drug development. Until recently, there have only been four primary classes of antifungals used to treat systemic fungal infections. Among these, azole antifungals are globally used because they are both inexpensive and effective. Due to various factors, resistance to antifungal drugs-especially azole antifungals-has developed in many <i>Candida</i> species, posing a significant public health threat. This review discusses the known mechanisms of azole antifungal resistance in <i>Candida albicans</i>, <i>Candida auris</i>, <i>Nakaseomyces glabrata</i>, <i>Candida tropicalis</i>, <i>Candida parapsilosis</i> and explores strategies to overcome the resistance problem.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf106"},"PeriodicalIF":3.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}