Journal of Antimicrobial Chemotherapy最新文献

{"title":"Correction to: Real-world data on long-acting intramuscular maintenance therapy with cabotegravir and rilpivirine mirror Phase 3 results.","authors":"","doi":"10.1093/jac/dkae372","DOIUrl":"10.1093/jac/dkae372","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466115","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":"Systematic review on oral antibacterial relay therapy for acute staphylococcal prosthetic joint infections treated with debridement, antibiotics and implant retention (DAIR).","authors":"Benoit Gachet, Agnès Dechartres, Eric Senneville, Olivier Robineau","doi":"10.1093/jac/dkae347","DOIUrl":"https://doi.org/10.1093/jac/dkae347","url":null,"abstract":"<p><strong>Background: </strong>The management of acute prosthetic joint infections (PJIs) often involves a debridement, antibiotics and implant retention (DAIR) strategy.</p><p><strong>Objective: </strong>Our objective was to conduct a systematic review and a network meta-analysis (NMA) to assess the comparative effectiveness of available oral antimicrobial regimens for the treatment of acute staphylococcal PJIs treated with DAIR.</p><p><strong>Methods: </strong>We conducted a systematic review searching articles from databases creation until 31 December 2023. We included articles on acute staphylococcal PJIs managed with DAIR with an oral antibiotic regimen relaying the initial management. The primary outcome was the remission rate.</p><p><strong>Results: </strong>Out of the 2421 studies screened, six studies completed the systematic review criteria: one randomized controlled trial and five observational studies. There was heterogeneity in patients' populations, duration and posology of treatments, definition of outcome and length of follow-up. Studies revealed 10 antibiotic regimens and most data focusing on five combinations recommended by the IDSA's guidelines: rifampicin associated to fluoroquinolone, clindamycin, cycline, linezolid or trimethoprim-sulfamethoxazole. Treatment comparisons were often secondary, without adjustment for confounding factors, resulting in a high risk of bias. Owing to inconsistencies a complete analysis, including an NMA was not possible.</p><p><strong>Conclusion: </strong>The available data highlight five companions to rifampicin, however, there is insufficient evidence to compare them. The literature does not provide a basis for rationalizing alternatives when rifampicin cannot be used.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390764","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: Impact of adequate empirical combination therapy on mortality in septic shock due to Pseudomonas aeruginosa bloodstream infections: a multicentre retrospective cohort study.","authors":"Caglayan Merve Ayaz, Özge Turhan","doi":"10.1093/jac/dkae366","DOIUrl":"10.1093/jac/dkae366","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A loading dose of clofazimine to rapidly achieve steady-state-like concentrations in patients with nontuberculous mycobacterial disease.","authors":"Ralf Stemkens, Arthur Lemson, Simon E Koele, Elin M Svensson, Lindsey H M Te Brake, Reinout van Crevel, Martin J Boeree, Wouter Hoefsloot, Jakko van Ingen, Rob E Aarnoutse","doi":"10.1093/jac/dkae309","DOIUrl":"https://doi.org/10.1093/jac/dkae309","url":null,"abstract":"<p><strong>Objectives: </strong>Clofazimine is a promising drug for the treatment of nontuberculous mycobacterial (NTM) diseases. Accumulation of clofazimine to reach steady-state plasma concentrations takes months. A loading dose may reduce the time to steady-state-like concentrations. We evaluated the pharmacokinetics (PK), safety and tolerability of a loading dose regimen in patients with NTM disease.</p><p><strong>Methods: </strong>Adult participants received a 4-week loading dose regimen of 300 mg clofazimine once daily, followed by a maintenance dose of 100 mg once daily (combined with other antimycobacterial drugs). Blood samples for PK analysis were collected on three occasions. A population PK model for clofazimine was developed and simulations were performed to assess the time to reach steady-state-like (target) concentrations for different dosing regimens.</p><p><strong>Results: </strong>Twelve participants were included. The geometric mean peak and trough clofazimine concentrations after the 4-week loading phase were 0.87 and 0.50 mg/L, respectively. Adverse events were common, but mostly mild and none led to discontinuation of clofazimine. Our loading dose regimen reduced the predicted median time to target concentrations by 1.5 months compared to no loading dose (3.8 versus 5.3 months). Further time benefit was predicted with a 6-week loading dose regimen (1.4 versus 5.3 months).</p><p><strong>Conclusion: </strong>A 4-week loading dose regimen of 300 mg once daily reduced the time to target clofazimine concentrations and was safe and well-tolerated. Extending the loading phase to 6 weeks could further decrease the time to target concentrations. Using a loading dose of clofazimine is a feasible strategy to optimize treatment of NTM disease.</p><p><strong>Clinical trials registration: </strong>NCT05294146.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390760","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":"Point-of-care tests to manage acute respiratory tract infections in primary care: a systematic review and qualitative synthesis of healthcare professional and patient views.","authors":"Melanie E Hoste, Aleksandra J Borek, Marta Santillo, Nia Roberts, Sarah Tonkin-Crine, Sibyl Anthierens","doi":"10.1093/jac/dkae349","DOIUrl":"https://doi.org/10.1093/jac/dkae349","url":null,"abstract":"<p><strong>Objectives: </strong>To review the evidence on healthcare professionals' (HCPs) and patients' views of the use of point-of-care tests (POCTs) in the management of acute respiratory tract infections (RTIs) in primary care settings.</p><p><strong>Methods: </strong>We conducted a systematic review of studies up to 28 April 2023. We included studies that included qualitative methods and results; focused on HCPs' and/or patients' views/experiences of POCTs for acute RTIs; and were conducted in primary care settings. We conducted a thematic synthesis to identify how their views on POCTs and interventions can support test use (PROSPERO registration: CRD42019150347).</p><p><strong>Results: </strong>We included 33 studies, developing 9 categories each for HCP and patient data. We identified 38 factors affecting POCT use: 28 from HCPs and 10 from patients. Factors exist outside and within consultations, and post-consultations, illustrating that some cannot be addressed by HCPs alone. Fourteen interventions were identified that could address factors and support POCT use, with 7 interventions appearing to address the most factors. Some interventions were beyond the scope of HCPs and patients and needed to be addressed at system and organizational levels. Both groups had mixed views on the use of POCTs and highlighted implementation challenges.</p><p><strong>Discussion: </strong>This review highlights numerous factors affecting POCT use in primary care. Policy-makers planning to implement POCTs are likely to achieve more by providing multi-faceted interventions that target factors outside, within, and post-consultation. Some interventions may need to be already established before POCT introduction. Whilst evidence beyond general practice is limited, similar factors suggest that similar context-tailored interventions would be appropriate.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390762","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":"Concentrations of ceftazidime and avibactam in bile fluid-a prospective phase IIb study.","authors":"Andrea Witowski, Lars Palmowski, Iris K Minichmayr, Markus Zeitlinger, Christoph Dorn, Constantin Lier, Michael Adamzik, Hartmuth Nowak, Tim Rahmel","doi":"10.1093/jac/dkae361","DOIUrl":"https://doi.org/10.1093/jac/dkae361","url":null,"abstract":"<p><strong>Background: </strong>The rise in carbapenem-resistant bacteria and the limited number of effective antibiotics pose a major health-care threat. The combination of ceftazidime (CAZ) and avibactam (AVI) represents an approved treatment option for carbapenem-resistant intra-abdominal infections. However, data on the pharmacokinetic profile of AVI in the hepatobiliary compartment is lacking.</p><p><strong>Objectives: </strong>To provide clinical in vivo data on the concentration of AVI in bile fluid as a surrogate for hepatobiliary excretion.</p><p><strong>Methods: </strong>A single dose of 2000/500 mg CAZ/AVI was administered prolonged over 2 h to 10 patients prior to abdominal surgery, with bile samples available in nine patients in this phase IIb study (DRKS-ID: DRKS00023533). Antibiotic concentrations in plasma (0-8 h), bile (after resection) and pharmacodynamic parameters were determined.</p><p><strong>Results: </strong>The mean concentration across individuals in bile was 33.5 mg/L (±20.5 mg/L) for CAZ and 7.1 mg/L (±3.5 mg/L) for AVI, resulting in bile/plasma ratios of 0.58 (±0.26) and 0.61 (±0.18). The Cmax in plasma was 87.2 mg/L (±25.0 mg/L) for CAZ and 18.6 mg/L (±6.29 mg/L) for AVI, with AUC0-∞ values of 351 h·mg/L (±104 h·mg/L) and 72.1 h·mg/L (±32.1 h·mg/L), respectively. Plasma concentrations of both CAZ and AVI remained more than 50% of the dosing interval above the minimum inhibitory concentrations (T>MIC > 50%; MICCAZ = 8 mg/L, MICAVI = 1 mg/L) in all patients. No antibiotic-associated side effects were reported during the 30-day follow-up.</p><p><strong>Conclusions: </strong>The concentrations of CAZ and AVI in bile suggest their potential as a valuable therapeutic option for multi-resistant biliary infections.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380908","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":"Target-site cefiderocol pharmacokinetics in soft tissues of healthy volunteers.","authors":"Maria Sanz-Codina, Wisse van Os, Anh Duc Pham, Anselm Jorda, Michael Wölf-Duchek, Felix Bergmann, Edith Lackner, Constantin Lier, J G Coen van Hasselt, Iris K Minichmayr, Christoph Dorn, Markus Zeitlinger, Valentin Al Jalali","doi":"10.1093/jac/dkae359","DOIUrl":"https://doi.org/10.1093/jac/dkae359","url":null,"abstract":"<p><strong>Background: </strong>Cefiderocol may potentially be used to treat skin and soft tissue infections (SSTIs). However, the pharmacokinetics of cefiderocol in human soft tissues have not yet been determined. The objective of the present PK study was to investigate whether target-site concentrations of cefiderocol are sufficiently high for the treatment of SSTIs.</p><p><strong>Methods: </strong>In this pharmacokinetic study, a single intravenous dose of 2 g cefiderocol was administered to eight healthy male volunteers. Drug concentrations were determined in plasma, muscle and subcutis over 8 h. Free plasma concentrations were calculated using the plasma protein binding determined with ultrafiltration. Free tissue concentrations were obtained using microdialysis. Penetration ratios were calculated as AUC0-8h_free_tissue/AUC0-8h_free_plasma. A population pharmacokinetic model was developed, and the probability of target attainment (PTA) was determined using Monte Carlo simulations.</p><p><strong>Results: </strong>Cefiderocol showed good tissue penetration, with mean penetration ratios ± standard deviation of 0.99 ± 0.33 and 0.92 ± 0.30 for subcutis and muscle, respectively. Cefiderocol pharmacokinetics in plasma were best described with a two-compartment model, and tissue concentrations were described by scaling the tissue concentrations to concentrations in the peripheral compartment of the plasma model. For a thrice-daily regimen with 2 g doses intravenously infused over 3 h, PTA was ≥90% for MIC values up to 4 mg/L, both based on free plasma and soft tissue pharmacokinetics.</p><p><strong>Conclusions: </strong>This study indicates that a dose of 2 g cefiderocol achieves concentrations in plasma considered sufficient for treating relevant bacterial species. Assuming a comparable PK/PD target for soft tissues, sufficiently high concentrations would also be achieved in soft tissues.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380910","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 effectiveness of early anti-SARS therapy in severely immunocompromised COVID-19 outpatients during the SARS-CoV-2 omicron variant era: a propensity score-adjusted retrospective cohort study.","authors":"Héctor Pinargote-Celorio, Óscar Moreno-Pérez, Pilar González-De-La-Aleja, Jara Llenas-García, Pedro María Martínez Pérez-Crespo, Juan-Carlos Rodríguez-Díaz, Belén Martínez-López, Nicolás Merchante Gutiérrez, José-Manuel Ramos-Rincón, Esperanza Merino","doi":"10.1093/jac/dkae351","DOIUrl":"https://doi.org/10.1093/jac/dkae351","url":null,"abstract":"<p><strong>Background: </strong>The effectiveness of the early treatment for antiviral agents in SARS-CoV-2 infection is closely related to patient comorbidities. Data on effectiveness in immunocompromised patients are limited, with reports involving highly heterogeneous and not well-defined populations. We aimed to assess the effectiveness of treatment in reducing hospitalizations in a real-world cohort of severely immunocompromised COVID-19 outpatients.</p><p><strong>Patients and methods: </strong>We conducted a multicentre, retrospective, observational cohort study of immunocompromised outpatients attended in infectious diseases departments from 1 January to 31 December 2022. Propensity score matching (PSM) multivariable logistic regression models were used to estimate the adjusted odds ratio [(aOR, 95% confidence interval (CI)] for the association between antiviral prescription and outcome (COVID-19-related hospitalization up to Day 90).</p><p><strong>Results: </strong>We identified 746 immunocompromised outpatients with confirmed SARS-CoV-2 infection. After eligibility criteria and PSM, a total of 410 patients were analysed: 205 receiving treatment (remdesivir, sotrovimab or nirmatrelvir/ritonavir) and 205 matched controls. Fifty-two patients required at least one COVID-19-related hospitalization 8 (3.9%) versus 44 (21.5%) in the antiviral and matched control cohorts, respectively. There were 13 deaths at 90 days, of which only 4 were COVID-19-related and none in the antiviral treatment group. After adjustment for residual confounders, the use of early therapy was associated with a protective effect on the risk of hospitalization [aOR 0.13 (0.05-0.29)], as was the use of biological immunomodulators [aOR 0.27 (0.10-0.74)], whereas chronic obstructive pulmonary disease [aOR 4.65 (1.09-19.69)] and anti-CD20 use [aOR 2.76 (1.31-5.81)] increased the odds.</p><p><strong>Conclusions: </strong>Early antiviral treatment was associated with a reduced risk of COVID-19-related hospitalization in ambulatory severely immunocompromised COVID-19 patients.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390763","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":"Suboptimal response to combination therapy with tixagevimab/cilgavimab and remdesivir for persistent SARS-CoV-2 infections in immunocompromised patients-authors' response.","authors":"Tzong-Yow Wu, Pao-Yu Chen, Jann-Tay Wang, Wang-Da Liu, Yee-Chun Chen, Shan-Chwen Chang","doi":"10.1093/jac/dkae357","DOIUrl":"10.1093/jac/dkae357","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The two-component sensor factor envZ influences antibiotic resistance and virulence in the evolutionary dynamics of multidrug-resistant Salmonella enteritidis causing multisite invasive infections.","authors":"Lifei Yu, Xinhong Han, Wang Zhang, Ying Fu, Shaoxue Yang, Shenghai Wu, Jie Jin, Siying Li, Yan Chen, Yan Jiang, Yunsong Yu","doi":"10.1093/jac/dkae355","DOIUrl":"https://doi.org/10.1093/jac/dkae355","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the impact of mutations in the two-component sensor envZ on antibiotic resistance and virulence in the evolutionary dynamics of MDR Salmonella enteritidis (S. enteritidis).</p><p><strong>Methods: </strong>Five S. enteritidis isolates obtained from a patient with multisite invasive infections were analysed. Analysis of antibiotic resistance genes, virulence genes and SNP was performed through WGS. RNA sequencing, quantitative RT-PCR, virulence testing in a Galleria mellonella (G. mellonella) infection model and in vitro cell experiments were used to examine the effects of envZ mutations.</p><p><strong>Results: </strong>WGS revealed identical resistance and virulence genes on an IncFIB(S)/IncFII(S)/IncX1 fusion plasmid in all strains. The faecal strains harboured envZ mutations, reducing outer membrane protein ompD and ompF transcriptional level. Virulence testing demonstrated elevated virulence in envZ mutant strains. In vitro experiments revealed increased adhesion, invasion and phagocytosis resistance in envZ mutants, along with reduced biofilm formation and growth rates.</p><p><strong>Conclusions: </strong>These findings highlight novel genetic locations on envZ influencing antibiotic resistance and virulence in clinical S. enteritidis strains. envZ mutations impact antibiotic resistance by down-regulating ompD and ompF expression and enhance virulence, contributing to multisite infections with increased fitness costs.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371938","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}