JAC-Antimicrobial Resistance最新文献

{"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}

{"title":"Characterisation of <i>in vitro</i> resistance selection against second-/last-line antibiotics in methicillin-resistant <i>Staphylococcus aureus</i> ATCC 43300 strain.","authors":"Anggia Prasetyoputri, Miranda E Pitt, Minh Duc Cao, Soumya Ramu, Angela Kavanagh, Alysha G Elliott, Devika Ganesamoorthy, Ian R Monk, Timothy P Stinear, Matthew A Cooper, Lachlan J M Coin, Mark A T Blaskovich","doi":"10.1093/jacamr/dlaf108","DOIUrl":"10.1093/jacamr/dlaf108","url":null,"abstract":"<p><strong>Background and objectives: </strong>The increasing occurrence of MRSA clinical isolates harbouring reduced susceptibility to mainstay antibiotics has escalated the use of second and last line antibiotics. Hence, it is critical to evaluate the likelihood of MRSA developing clinical resistance to these antibiotics. Our study sought to characterize the development of resistance to vancomycin (VAN), daptomycin (DAP) and linezolid (LZD) in MRSA ATCC 43300 <i>in vitro</i> and further determine the mechanisms underpinning resistance.</p><p><strong>Methods: </strong>MRSA was exposed to increasing concentrations of VAN, DAP and LZD for 20 days, with eight replicates for each antibiotic conducted in parallel. The resulting day 20 (D20) isolates were subjected to antimicrobial susceptibility testing, whole genome sequencing, autolysis assays, and growth curves to determine bacterial fitness.</p><p><strong>Results: </strong>Exposure to VAN or LZD for 20 days resulted in a subtle 2-fold increase in the MIC, whereas DAP exposure yielded DAP-non-susceptible isolates with up to 16-fold MIC increase. The MIC increase was accompanied by variable changes in relative fitness and reduced resistance to autolysis in some isolates. D20 isolates harboured mutations in genes commonly associated with resistance to the respective antibiotics (e.g. <i>walK</i> for VAN, <i>mprF</i> and <i>rpoB</i> for DAP, <i>rplC</i> for LZD), along with several previously unreported variants. Introduction of key mutations to these identified genes in the parental strain via allelic exchange confirmed their role in the development of resistance.</p><p><strong>Conclusions: </strong><i>In vitro</i> selection against VAN, DAP or LZD resulted in the acquisition of mutations similar to those correlated with clinical resistance, including the associated phenotypic alterations.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf108"},"PeriodicalIF":3.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527991","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":"Comparative <i>in vitro</i> activity of sulbactam with avibactam or durlobactam against carbapenem-resistant <i>Acinetobacter baumannii</i>.","authors":"Ava J Dorazio, Ellen G Kline, Kevin M Squires, Marissa P Griffith, Yohei Doi, Ryan K Shields","doi":"10.1093/jacamr/dlaf098","DOIUrl":"10.1093/jacamr/dlaf098","url":null,"abstract":"<p><strong>Objective: </strong>To determine the <i>in vitro</i> activity of sulbactam in combination with avibactam or durlobactam with and without meropenem or imipenem against carbapenem-resistant <i>Acinetobacter baumannii</i> clinical isolates.</p><p><strong>Methods: </strong>Standardized susceptibility testing by broth microdilution was performed to determine MICs for imipenem, meropenem and sulbactam alone, and for combinations including sulbactam/avibactam, sulbactam/durlobactam, sulbactam/avibactam/meropenem, sulbactam/avibactam/imipenem, sulbactam/durlobactacm/meropenem and sulbactam/durlobactam/imipenem. Whole-genome sequencing was also performed to compare MICs to key resistance determinants, including mutations in penicillin-binding proteins (PBPs).</p><p><strong>Results: </strong>Median sulbactam/durlobactam and sulbactam/avibactam MICs were 2 and 16 mg/L, respectively. Imipenem potentiated the <i>in vitro</i> activity of both combinations to a greater extent than meropenem corresponding to median sulbactam/durlobactam/imipenem and sulbactam/avibactam/imipenem MICs of 1 and 8 mg/L, respectively. Carbapenem combinations were more active than combinations without a carbapenem against isolates with PBP3 mutations.</p><p><strong>Conclusions: </strong>These data show that imipenem potentiates sulbactam-based combinations to a greater extent than meropenem; however, future studies are needed to define how these data should be applied in clinical practice.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf098"},"PeriodicalIF":3.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527993","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":"Clinical efficacy, safety and pharmacokinetics of novel β-lactam/β-lactamase inhibitor combinations: a systematic review.","authors":"Ana Alarcia-Lacalle, Andrés Canut-Blasco, María Ángeles Solinís, Arantxa Isla, Alicia Rodríguez-Gascón","doi":"10.1093/jacamr/dlaf096","DOIUrl":"10.1093/jacamr/dlaf096","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial resistance is a global public health threat that requires urgent solutions. One strategy to decrease resistance of Gram-negative bacteria (GNB) to β-lactam antibiotics (BL) is their combination with β-lactamase inhibitors (BLI).</p><p><strong>Objectives: </strong>This systematic review analyses the outcomes, safety and pharmacokinetics (PK) of recently approved or under clinical development BLI and BL/BLI combinations.</p><p><strong>Methods: </strong>The systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PubMed, Embase, and Cochrane electronic databases were used to search for articles from January 2010 to November 2024. The studies were retrieved and screened on the basis of predefined exclusion and inclusion criteria. A quality assessment of the included studies was conducted following the New Castle-Ottawa Scale.</p><p><strong>Results: </strong>A total of 191 articles addressing clinical research regarding the efficacy, safety, tolerability, and PK of new BL/BLI combinations with avibactam, durlobactam, enmetazobactam, nacubactam, relebactam, taniborbactam, tazobactam, vaborbactam and zidebactam were included. According to the published literature, clinical research supports the novel BL/BLI combinations for the treatment of complicated urinary tract infections, complicated intra-abdominal infections, and hospital-acquired and ventilator-associated pneumonia (HAP/VAP) caused by GNB. In spite of that, the development of new BLI effective for class B metallo-β-lactamases (MBL) is still challenging, being aztreonam/avibactam the only approved combination active against MBL-producing bacteria.</p><p><strong>Conclusions: </strong>Although there has been extensive research to develop new BLI and BL/BLI combinations, only a few have reached the market. More evidence of its usefulness in the real world is still needed.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf096"},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527992","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":"Over-the-counter antimicrobial dispensing in Lusaka Province retail pharmacies, Zambia.","authors":"Kelly Chisanga, Ernest Simpemba, Chipwaila Chunga, Victor Chalwe, Otridah Kapona, Winfredah Nyirenda, James Mwansa, Godfrey Biemba","doi":"10.1093/jacamr/dlaf092","DOIUrl":"10.1093/jacamr/dlaf092","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial resistance (AMR) is a major global threat, projected to cause 10 million deaths annually by 2050, mostly in sub-Saharan Africa. Indiscriminate dispensing and policy non-adherence worsen AMR, yet non-prescription antimicrobial use persists. This study examines over-the-counter (OTC) antimicrobial dispensing by pharmacy personnel in Lusaka Province, Zambia.</p><p><strong>Objective: </strong>To describe OTC antimicrobial dispensing by retail pharmacy personnel in Lusaka Province and its implications for AMR.</p><p><strong>Methods: </strong>We conducted a cross-sectional survey using simulated clients at 142 retail pharmacies to assess OTC antimicrobial dispensing practices.</p><p><strong>Results: </strong>Of the 142 retail pharmacies in Lusaka visited by simulation clients seeking antimicrobials without prescriptions, 90.1% complied with the requests. While 28.9% mentioned that a prescription was needed, only 25.4% advised clients to obtain one. Additionally, 83.3% recommended buying antimicrobials instead of visiting a hospital, with in-pharmacy treatment rates of 86.7% for Upper Respiratory Tract Infection symptoms, 90.5% for cough and 91.7% for sore throat.</p><p><strong>Conclusions: </strong>We observed a high level of OTC antimicrobial dispensing among retail pharmacy personnel in Lusaka Province, which may hinder efforts to combat AMR in Zambia. Although the study lacked qualitative data to explore the reasons behind this practice, such research is urgently needed. Nonetheless, our findings highlight the need for the ZMRA to enhance monitoring of retail pharmacies to ensure adherence to international antimicrobial dispensing standards and help reduce AMR.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf092"},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527996","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 ceftazidime/avibactam in combination with colistin against KPC-2-producing <i>Klebsiella pneumoniae</i> in static and dynamic time-kill experiments.","authors":"Lisa Allander, Emma Vikdahl, Margarita Chatzopoulou, Amaury O'Jeanson, Linus Sandegren, Pernilla Lagerbäck, Thomas Tängdén","doi":"10.1093/jacamr/dlaf105","DOIUrl":"10.1093/jacamr/dlaf105","url":null,"abstract":"<p><strong>Objectives: </strong>Ceftazidime/avibactam is used for severe infections caused by carbapenemase-producing <i>Klebsiella pneumoniae</i>. Combination therapy with older antibiotics is frequently used, but the supporting data are limited. This study aimed to evaluate ceftazidime/avibactam in combination with colistin against KPC-2-producing <i>K. pneumoniae</i>.</p><p><strong>Material and methods: </strong>Five clinical KPC-2-producing <i>K. pneumoniae</i> strains were characterized by phenotypic antibiotic susceptibility testing and whole-genome sequencing. Single antibiotics and combinations were evaluated in 24-h static time-kill experiments with ceftazidime/avibactam concentrations of 0.5× MIC_ratio and colistin at 0.5× and 1× MIC. One strain was subjected to 32-h dynamic time-kill experiments with ceftazidime/avibactam at concentrations mimicking patient pharmacokinetics in plasma and colistin added to 1 mg/L, i.e. the average free steady-state concentration. Population analysis was performed at 0, 16, and 32 h by plating at 4× and 8× MIC_ratio (ceftazidime/avibactam) or MIC (colistin) to assess resistance development.</p><p><strong>Results: </strong>All strains were susceptible to ceftazidime/avibactam and colistin, had mutations in <i>ompK35</i> and <i>ompK36</i>, and carried multiple β-lactamase genes. Ceftazidime/avibactam combined with colistin demonstrated 24-h synergy in static time-kill experiments against 3 of 5 strains. Although ceftazidime/avibactam and colistin alone showed rapid initial killing in the dynamic experiments, regrowth occurred after 4-8 h. The three-drug combination displayed a bactericidal effect and synergy at 14-32 h. Resistance development resulting in 64-fold MIC increases was observed in experiments with colistin alone.</p><p><strong>Conclusions: </strong>This study showed synergy with ceftazidime/avibactam and colistin against KPC-2-producing <i>K. pneumoniae</i> at clinically relevant concentrations. More studies are warranted to investigate the clinical potential of this combination.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf105"},"PeriodicalIF":3.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527995","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>Escherichia coli</i> producing AmpC DHA-1 bacteraemia in neutropenic leukemic patient: continuous infusion ceftazidime/avibactam as a carbapenem sparing regimen.","authors":"S Giuliano, A Piccirilli, J Angelini, F Patriarca, R Fanin, L Martini, T Semenzin, M Fanin, S Lanini, R A Bonomo, M Perilli, C Tascini","doi":"10.1093/jacamr/dlaf109","DOIUrl":"10.1093/jacamr/dlaf109","url":null,"abstract":"<p><strong>Background: </strong><i>Escherichia coli</i> resistant to third-generation cephalosporins, primarily due to the production of ESBLs and AmpC β-lactamases, poses a significant therapeutic challenge, particularly in immunocompromised patients. Ceftazidime/avibactam (CZA) has emerged as a potential carbapenem-sparing option, though data on its efficacy against AmpC-producing Enterobacterales remain limited.</p><p><strong>Methods: </strong>We report a case of bloodstream infection (BSI) caused by an <i>E. coli</i> strain harbouring the plasmid-mediated AmpC enzyme DHA-1 in a neutropenic patient following allogeneic haematopoietic stem cell transplantation. The strain was characterized via whole-genome sequencing and conjugation assays. Therapeutic drug monitoring (TDM) was used to guide a continuous infusion CZA regimen in the context of augmented renal clearance (ARC).</p><p><strong>Results: </strong>The patient responded favourably to CZA therapy (2.5 g every 8 h via continuous infusion for 9 days), with rapid microbiological clearance and clinical improvement. TDM confirmed therapeutic plasma concentrations of both ceftazidime (29.57 mg/L) and avibactam (5.52 mg/L). Genomic analysis revealed multiple resistance genes (<i>blaDHA-1</i>, <i>qnrB4</i>, <i>mphA</i>, <i>dfrA7</i>) and virulence factors, with the isolate identified as <i>E. coli</i> ST442, serotype O174:H9. The early switch from meropenem to CZA may have contributed to microbiota preservation and prevented subsequent infection by carbapenemase-producing <i>Klebsiella pneumoniae</i>, for which the patient was colonized.</p><p><strong>Conclusions: </strong>This case illustrates the clinical utility of a carbapenem-sparing strategy guided by TDM in a high-risk, ARC patient with an AmpC-producing <i>E. coli</i> BSI. Continuous infusion CZA achieved pharmacokinetic/pharmacodynamic targets associated with therapeutic success, offering a promising alternative to carbapenems while mitigating the risk of resistance development and microbiota disruption.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf109"},"PeriodicalIF":3.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527990","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":"Eravacycline as a last resort for difficult-to-treat resistant <i>Acinetobacter baumannii</i> infections in critically ill patients: three case reports with pharmacokinetic insights.","authors":"Leo Mimram, Jean-François Timsit, Emilie Rondinaud, Minh Le, Michael Thy","doi":"10.1093/jacamr/dlaf095","DOIUrl":"10.1093/jacamr/dlaf095","url":null,"abstract":"<p><strong>Objectives: </strong>To describe eravacycline use as a salvage treatment for ventilator-associated pneumonia (VAP) caused by difficult-to-treat resistant (DTR) <i>Acinetobacter baumannii</i> in critically ill patients.</p><p><strong>Methods: </strong>We reported three cases of DTR <i>A. baumannii</i> VAP with multiple organ failure treated with eravacycline. Patients were critically ill with confirmed VAP by distal pulmonary cultures. Eravacycline was administered at 1 mg/kg q12h in combination with IV colistin or as primary therapy. Clinical and microbiological outcomes were assessed.</p><p><strong>Results: </strong>Eravacycline MICs ranged from 0.25 to 0.75 mg/L. Microbiological success was observed in the three cases, including one patient who was successfully weaned and discharged alive with no further samples submitted for microbiological culture, and two other patients who were repeatedly sampled and remained negative for <i>A. baumannii</i>. Clinical success could not be confirmed in one case. No adverse effects were observed. Pharmacokinetic analysis of concentrations from a single patient revealed a maximal concentration (<i>C</i> _max) of 1.47 mg/L at 1 h and an AUC_0-6 of 2.88 mg·h/L. The epithelial lining fluid/plasma concentration ratio was 0.1.</p><p><strong>Conclusions: </strong>Eravacycline showed promise as a salvage therapy for DTR <i>A. baumannii</i> VAP in critically ill patients. Further studies are needed to confirm its efficacy and optimal dosing in this setting.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf095"},"PeriodicalIF":3.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527994","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}