Journal of Antimicrobial Chemotherapy最新文献

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Evaluation of an optimized intermittent vancomycin dosing regimen in infants.
IF 3.9 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2025-04-04 DOI: 10.1093/jac/dkaf112
Amanda L Wilkins, Wenyu Yang, Stephen B Duffull, Noel Cranswick, Nigel Curtis, Xiao Zhu, Amanda Gwee
{"title":"Evaluation of an optimized intermittent vancomycin dosing regimen in infants.","authors":"Amanda L Wilkins, Wenyu Yang, Stephen B Duffull, Noel Cranswick, Nigel Curtis, Xiao Zhu, Amanda Gwee","doi":"10.1093/jac/dkaf112","DOIUrl":"https://doi.org/10.1093/jac/dkaf112","url":null,"abstract":"<p><strong>Background: </strong>Many standard intermittent dosing regimens for vancomycin in infants fail to achieve the therapeutic target at steady state. This study used population pharmacokinetic (popPK) modelling and simulation to determine an optimized vancomycin dosing regimen, and clinically evaluated this regimen in infants aged 0-90 days.</p><p><strong>Methods: </strong>An optimized model-based dosing regimen to achieve an AUC24 of 400-650 mg/L·h was developed from a published vancomycin popPK model. The PTA of achieving the AUC24 target as well as a trough concentration of 10-20 mg/L (still commonly used in clinical practice as a surrogate for AUC24) was determined. This dosing regimen was implemented at The Royal Children's Hospital Melbourne, and evaluated over a 12 month period to determine the proportion of infants achieving the target AUC24 and trough concentration at steady state.</p><p><strong>Results: </strong>Using the validated model, the simulated PTA of achieving the target AUC24 and trough concentration with the optimized dosing regimen was 68% and 56%, respectively. This dosing regimen was clinically evaluated in 24 infants who received 26 vancomycin courses (median postmenstrual age 40 weeks, range 25-53; median weight 3250 g, range 650-5930). In 23/26 (88%) courses, the target AUC24 was achieved, with 2/26 (8%) and 1/26 (4%) having subtherapeutic and supratherapeutic AUC24, respectively. The first trough concentration taken at steady state was between 10 and 20 mg/L in 21/26 (81%) courses. No nephrotoxicity or ototoxicity was observed.</p><p><strong>Conclusions: </strong>Our optimized vancomycin dosing regimen for infants aged 0-90 days achieved the target AUC24 in 88% and should be considered for routine use.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779730","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}
引用次数: 0
Unravelling the genetic contributors to linezolid resistance in Mycobacterium smegmatis: insights from a transposon library.
IF 3.9 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2025-04-03 DOI: 10.1093/jac/dkaf106
Dachuan Lin, Yuanyi Zhang, Zhifei Luo, Jing Wang, Xinchun Chen
{"title":"Unravelling the genetic contributors to linezolid resistance in Mycobacterium smegmatis: insights from a transposon library.","authors":"Dachuan Lin, Yuanyi Zhang, Zhifei Luo, Jing Wang, Xinchun Chen","doi":"10.1093/jac/dkaf106","DOIUrl":"https://doi.org/10.1093/jac/dkaf106","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to identify and characterize genes associated with linezolid resistance in Mycobacterium smegmatis using a transposon mutagenesis approach.</p><p><strong>Methods: </strong>This research conducted three replicative experiments where 16 isolates displaying pronounced resistance to linezolid were examined, revealing two distinct morphologies. WGS was employed to investigate these isolates, uncovering mutations in specific genes. The binding affinity of linezolid to relevant proteins was assessed through molecular docking studies and validated by drug affinity responsive target stability (DARTS) assays.</p><p><strong>Results: </strong>Complementation of the mspA gene in mutant strains restored linezolid susceptibility, but the Ala127Gln substitution in MSMEG_0965 did not, suggesting a critical role of this residue in resistance. Further investigations revealed that the resistance mechanism in the △MSMEG_0965 mutant involves impaired linezolid uptake.</p><p><strong>Conclusions: </strong>The research successfully identified two genes, MSMEG_4189 and MSMEG_0965, associated with linezolid resistance in M. smegmatis. It also elucidated the role of MSMEG_0965 in the resistance mechanism, providing significant targets and reference points for future studies on clinical strains.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772386","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}
引用次数: 0
In vitro, intracellular and in vivo synergy between amoxicillin, imipenem and relebactam against Mycobacterium abscessus.
IF 3.9 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2025-04-03 DOI: 10.1093/jac/dkaf101
Maria Bitar, Vincent Le Moigne, Jean-Louis Herrmann, Michel Arthur, Jean-Luc Mainardi
{"title":"In vitro, intracellular and in vivo synergy between amoxicillin, imipenem and relebactam against Mycobacterium abscessus.","authors":"Maria Bitar, Vincent Le Moigne, Jean-Louis Herrmann, Michel Arthur, Jean-Luc Mainardi","doi":"10.1093/jac/dkaf101","DOIUrl":"https://doi.org/10.1093/jac/dkaf101","url":null,"abstract":"<p><strong>Objectives: </strong>Mycobacterium abscessus is the most frequent of the rapidly growing mycobacteria responsible for lung infections in patients suffering from cystic fibrosis and COPD. Imipenem is currently recommended in the treatment of these infections in spite of β-lactamase production. Since the targets of β-lactams include transpeptidases of both the l,d and d,d specificities, we tested, in vitro, intracellularly and in vivo, a combination of two β-lactams active on these enzymes, amoxicillin and imipenem, alone or in combination with the β-lactamase inhibitor relebactam.</p><p><strong>Methods: </strong>Drug combinations were evaluated against M. abscessus CIP 104536T and clinical isolates (n = 35) by determining MICs, FIC indices and time-killing. Drug combinations were also evaluated in macrophages and in mice.</p><p><strong>Results: </strong>In the presence of relebactam, synergy between amoxicillin and imipenem was observed against both M. abscessus CIP 104536T and the clinical isolates. Against M. abscessus CIP 104536T, the addition of 1 mg/L imipenem and 4 mg/L relebactam led to a decrease in the MIC of amoxicillin from 64 to 1 mg/L. The triple combination was active in vitro and intracellularly (a 4.30 decrease in the log10 cfu/mL and 82% killing, respectively). The triple combination was effective in reducing log10 cfu in mouse organs and mouse spleen weights, and in preventing losses in mouse weights.</p><p><strong>Conclusions: </strong>The amoxicillin/imipenem/relebactam combination was synergistic in vitro and effective in vivo against M. abscessus. Since these drugs are clinically available, the triple combination should be considered by clinicians and further evaluated based on the reporting of the patient outcomes.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772383","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}
引用次数: 0
Population pharmacokinetics and optimized prophylaxis dosing of cefazolin during transcatheter aortic valve implantation.
IF 3.9 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2025-04-03 DOI: 10.1093/jac/dkaf108
C Robson, X Liu, O Al-Mukhtar, S C Wallis, H Won, J Ordonez, R Gooley, R L Stuart, S J Nicholls, J A Roberts, B A Rogers
{"title":"Population pharmacokinetics and optimized prophylaxis dosing of cefazolin during transcatheter aortic valve implantation.","authors":"C Robson, X Liu, O Al-Mukhtar, S C Wallis, H Won, J Ordonez, R Gooley, R L Stuart, S J Nicholls, J A Roberts, B A Rogers","doi":"10.1093/jac/dkaf108","DOIUrl":"https://doi.org/10.1093/jac/dkaf108","url":null,"abstract":"<p><strong>Background: </strong>Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical valve replacement for aortic stenosis. Infective endocarditis, most often caused by enterococci, is a significant post-procedural complication. Cefazolin has been the most frequently utilized agent for TAVI procedural prophylaxis, although recent guidelines suggest addition of an agent with enterococcal activity. Optimizing antimicrobial prophylaxis is important but little is known about antibiotic pharmacokinetics (PK) in this procedure.</p><p><strong>Objectives: </strong>To define the population PK profile of prophylactic cefazolin in TAVI procedures and determine appropriateness for use.</p><p><strong>Methods: </strong>Adult patients receiving cefazolin prophylaxis for TAVI were enrolled. Serum was collected at four timepoints periprocedurally for analysis of cefazolin concentrations. Population PK analysis and Monte Carlo simulation was performed. Fractional target attainment (FTA) against MIC distributions for common pathogens was performed.</p><p><strong>Results: </strong>Three hundred and fifty-nine plasma cefazolin concentrations (188 total, 171 unbound) from 50 participants were used for model development. PTA for a 2 g dose of cefazolin and a procedure of 2 h duration was >90% for organisms with an MIC up to 8 mg/L. FTA was 100% for MSSA at all examined procedure durations and estimated glomerular filtration rate levels. FTAs for Staphylococcus epidermidis and Enterococcus faecalis, based on limited MIC data, were predominantly subthreshold.</p><p><strong>Conclusions: </strong>This study found a 2 g dose of cefazolin achieved target exposure for MSSA but was subthreshold for other pathogens.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772384","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}
引用次数: 0
Holistic analysis of the determinants of antibiotic prescription in primary care in France: a cross-sectional study with nationwide panel data.
IF 3.9 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2025-04-03 DOI: 10.1093/jac/dkaf102
Emmanuel Piednoir, Pascal Thibon, Lea Messidor, Ludivine Launay, Renaud Verdon, Pierre Tattevin
{"title":"Holistic analysis of the determinants of antibiotic prescription in primary care in France: a cross-sectional study with nationwide panel data.","authors":"Emmanuel Piednoir, Pascal Thibon, Lea Messidor, Ludivine Launay, Renaud Verdon, Pierre Tattevin","doi":"10.1093/jac/dkaf102","DOIUrl":"https://doi.org/10.1093/jac/dkaf102","url":null,"abstract":"<p><strong>Objectives: </strong>Antimicrobial resistance (AMR) is a critical public health issue, with overuse of antibiotics being a key driver. This study aimed to examine the determinants of antibiotic prescription in primary care in France, using nationwide panel data from 2022.</p><p><strong>Methods: </strong>Data were obtained from several open sources. Antibiotic consumption was measured by the number of prescriptions of all systemic antibiotics per 1000 inhabitants, and patient, physician, healthcare system and seasonal viral outbreak (influenza and COVID-19) were considered as potential related factors. We then performed a linear multivariate regression model.</p><p><strong>Results: </strong>The main findings were that patients <15 years (β = 7.36, P < 0.001), females (β = 9.54, P = 0.01), those with chronic diseases (β = 16.29, P < 0.001), white-collar workers (β = 3.40, P < 0.001) and European Deprivation Index score (β = 4.19, P < 0.001) had higher antibiotic prescription rates. Older physicians (age > 50 years: β = 1.35, P < 0.001) and those practising in areas with higher healthcare accessibility (Local Potential Accessibility score: β = 40.93, P < 0.001) were also associated with higher prescription volumes. In contrast, female physicians were linked to lower prescription rates (β = -0.62, P = 0.002).</p><p><strong>Conclusions: </strong>The study emphasizes the complexity of antibiotic prescription behaviours, showing that both clinical and non-clinical factors contribute to prescription patterns. It also highlights social and accessibility factors as significant drivers of antibiotic use. In order to be effective, strategies for the correct use of antibiotics must account for these different aspects.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772380","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}
引用次数: 0
Estimating the herd effects of antimicrobial prevention interventions on ventilator-associated pneumonia within ICU populations: a cluster randomized trial emulation using data from Cochrane reviews.
IF 3.9 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2025-04-02 DOI: 10.1093/jac/dkaf033
James C Hurley
{"title":"Estimating the herd effects of antimicrobial prevention interventions on ventilator-associated pneumonia within ICU populations: a cluster randomized trial emulation using data from Cochrane reviews.","authors":"James C Hurley","doi":"10.1093/jac/dkaf033","DOIUrl":"10.1093/jac/dkaf033","url":null,"abstract":"<p><strong>Background: </strong>The herd effects of antimicrobial interventions used to prevent ICU-acquired infections are unknown. The objective here was to estimate these herd effects within a single three-tiered cluster randomized trial (CRT) emulated using ventilator-associated pneumonia (VAP) data from randomized concurrent control trials (RCCTs) abstracted within Cochrane reviews.</p><p><strong>Methods: </strong>Control and intervention group data derived from 13 Cochrane reviews of 72 RCCTs of antibiotic (Tier 3) and antiseptic (Tier 2) decontamination versus 109 RCCTs of various non-decontamination (Tier 1, serving as benchmark) VAP prevention interventions were arranged as a three-tiered CRT. The direct and indirect (herd) effects of Tiers 2 and 3 each versus Tier 1 interventions were obtained using estimators derived in meta-regression models.</p><p><strong>Results: </strong>Benchmark (Tier 1) VAP incidences derived for control and intervention groups from non-decontamination RCCTs were 23.3 (95% CI: 20.6-26.1; n = 111) and 19.2 (95% CI: 16.8-21.8; n = 112), respectively. The mean VAP incidences for antibiotic and antiseptic decontamination control groups were 5% to 15% higher than the control group benchmark. The direct effects of antibiotic and antiseptic interventions versus Tier 1 benchmarks (ORs) were 0.77 (95% CI: 0.55-1.09) and 0.97 (95% CI: 0.71-1.33) whereas the indirect effects were 2.17 (95% CI: 1.56-3.03) and 1.38 (95% CI: 1.0-1.91), respectively.</p><p><strong>Conclusions: </strong>Indirect (herd) effects from antimicrobial interventions, although inapparent within individual RCCTs, are strong. These effects on control group VAP incidences, which spuriously conflate the appearance of benefit, constitute herd peril.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1047-1058"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
General practice antibiotic prescriptions attributable to respiratory syncytial virus by age and antibiotic class: an ecological analysis of the English population.
IF 3.9 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2025-04-02 DOI: 10.1093/jac/dkaf043
Lucy Miller, Thomas Beaney, Russell Hope, Mark Cunningham, Julie V Robotham, Koen B Pouwels, Cèire E Costelloe
{"title":"General practice antibiotic prescriptions attributable to respiratory syncytial virus by age and antibiotic class: an ecological analysis of the English population.","authors":"Lucy Miller, Thomas Beaney, Russell Hope, Mark Cunningham, Julie V Robotham, Koen B Pouwels, Cèire E Costelloe","doi":"10.1093/jac/dkaf043","DOIUrl":"10.1093/jac/dkaf043","url":null,"abstract":"<p><strong>Background: </strong>Respiratory syncytial virus (RSV) may contribute to a substantial volume of antibiotic prescriptions in primary care. However, data on the type of antibiotics prescribed for such infections are only available for children <5 years in the UK. Understanding the contribution of RSV to antibiotic prescribing would facilitate predicting the impact of RSV preventative measures on antibiotic use and resistance. The objective of this study was to estimate the proportion of antibiotic prescriptions in English general practice attributable to RSV by age and antibiotic class.</p><p><strong>Methods: </strong>Generalized additive models examined associations between weekly counts of general practice antibiotic prescriptions and laboratory-confirmed respiratory infections from 2015 to 2018, adjusting for temperature, practice holidays and remaining seasonal confounders. We used general practice records from the Clinical Practice Research Datalink and microbiology tests for RSV, influenza, rhinovirus, adenovirus, parainfluenza, human metapneumovirus, Mycoplasma pneumoniae and Streptococcus pneumoniae from England's Second Generation Surveillance System.</p><p><strong>Results: </strong>An estimated 2.1% of antibiotics were attributable to RSV, equating to an average of 640 000 prescriptions annually. Of these, adults ≥75 years contributed to the greatest volume, with an annual average of 149 078 (95% credible interval: 93 733-206 045). Infants 6-23 months had the highest average annual rate at 6580 prescriptions per 100 000 individuals (95% credible interval: 4522-8651). Most RSV-attributable antibiotic prescriptions were penicillins, macrolides or tetracyclines. Adults ≥65 years had a wider range of antibiotic classes associated with RSV compared with younger age groups.</p><p><strong>Conclusions: </strong>Interventions to reduce the burden of RSV, particularly in older adults, could complement current strategies to reduce antibiotic use in England.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1116-1126"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pharmacokinetics and safety of rifapentine in children: dosing for latent tuberculosis infection.
IF 3.9 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2025-04-02 DOI: 10.1093/jac/dkaf029
Weijian Liu, Nuo Xu, Wei Li, Wen Yao Mak, Tian He, Hongjuan Qin, Shuihua Lu, Hongzhou Lu, Xiaoqiang Xiang, Xiao Zhu, Peize Zhang
{"title":"Pharmacokinetics and safety of rifapentine in children: dosing for latent tuberculosis infection.","authors":"Weijian Liu, Nuo Xu, Wei Li, Wen Yao Mak, Tian He, Hongjuan Qin, Shuihua Lu, Hongzhou Lu, Xiaoqiang Xiang, Xiao Zhu, Peize Zhang","doi":"10.1093/jac/dkaf029","DOIUrl":"10.1093/jac/dkaf029","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the safety of 4-week daily rifapentine-isoniazid regimen in latent tuberculosis for Chinese children, and to provide paediatric-specific evidence for extrapolating adult dosing strategies to children.</p><p><strong>Methods: </strong>An open-label, prospective, single-arm clinical trial was conducted among eligible patients (aged <10 years old). Rifapentine concentrations and laboratory safety biomarker (total bilirubin) were analysed and used for population pharmacokinetic-toxicity model development. Simulations were performed to compare efficacy and safety of weight-based and flat-dosing strategy.</p><p><strong>Results: </strong>Once-daily rifapentine treatment was well tolerated: 310 samples (rifapentine n = 139; total bilirubin n = 171) from 36 children (age range 0.89-10 years) were captured well by a joint one-compartment pharmacokinetic with time-varying clearance and an indirect response model. The model adequately described rifapentine autoinduction, reaching a plateau after 21 days and increasing clearance by 70.4%. Simulation suggested that weight-based dosing may cause underexposure in children under 14.5 kg. A flat-dosing strategy could ensure plasma levels within the therapeutic windows. Rifapentine's impact on total bilirubin was within a 2-fold range, and the effect subsided within 5 days after discontinuation.</p><p><strong>Conclusions: </strong>Our study suggested that a flat-dosing strategy of rifapentine was potentially safe and effective for latent tuberculosis infection treatment in Chinese children aged 1 to 10 years old.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1022-1030"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408071","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}
引用次数: 0
Effect of empiric antibiotics against Pseudomonas aeruginosa on mortality in hospitalized patients: a systematic review and meta-analysis-authors' response.
IF 3.9 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2025-04-02 DOI: 10.1093/jac/dkaf047
Cameron J Hunter, Elizabeth A Marhoffer, Jürgen L Holleck, Samer Ein Alshaeba, Alyssa A Grimshaw, Andrew Chou, George B Carey, Craig G Gunderson
{"title":"Effect of empiric antibiotics against Pseudomonas aeruginosa on mortality in hospitalized patients: a systematic review and meta-analysis-authors' response.","authors":"Cameron J Hunter, Elizabeth A Marhoffer, Jürgen L Holleck, Samer Ein Alshaeba, Alyssa A Grimshaw, Andrew Chou, George B Carey, Craig G Gunderson","doi":"10.1093/jac/dkaf047","DOIUrl":"10.1093/jac/dkaf047","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1162"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458016","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}
引用次数: 0
Validation of the REverSe TRanscrIptase Chain Termination assay for measuring tenofovir diphosphate in dried blood spots from a clinical pharmacokinetic trial.
IF 3.9 2区 医学
Journal of Antimicrobial Chemotherapy Pub Date : 2025-04-02 DOI: 10.1093/jac/dkaf049
Benjamin P Sullivan, Cosette A Craig, Andrew T Bender, Emily Blake, Oraphan Siriprakaisil, Pra-Ornsuda Sukrakanchana, Tim R Cressey, Paul K Drain, Ayokunle O Olanrewaju, Jonathan D Posner
{"title":"Validation of the REverSe TRanscrIptase Chain Termination assay for measuring tenofovir diphosphate in dried blood spots from a clinical pharmacokinetic trial.","authors":"Benjamin P Sullivan, Cosette A Craig, Andrew T Bender, Emily Blake, Oraphan Siriprakaisil, Pra-Ornsuda Sukrakanchana, Tim R Cressey, Paul K Drain, Ayokunle O Olanrewaju, Jonathan D Posner","doi":"10.1093/jac/dkaf049","DOIUrl":"10.1093/jac/dkaf049","url":null,"abstract":"<p><strong>Background: </strong>Tenofovir diphosphate concentration in red blood cells is an objective measure of long-term oral pre-exposure prophylaxis (PrEP) or antiretroviral therapy (ART) adherence. However, current methods for measuring tenofovir diphosphate are equipment and capital intensive, limiting widespread adoption.</p><p><strong>Objectives: </strong>Low cost, rapid diagnostics for measuring tenofovir diphosphate may drive clinical adoption of routine drug level measurement as a tool for adherence monitoring of tenofovir disoproxil fumarate-based PrEP or ART. We validate a simple and accessible enzymatic assay [REverSe TRanscrIptase Chain Termination (RESTRICT)] for measuring tenofovir diphosphate in dried blood spots (DBS) obtained from a directly observed therapy study of individuals on PrEP.</p><p><strong>Methods: </strong>We performed RESTRICT measurements on 74 DBS samples from individuals on tenofovir disoproxil fumarate/emtricitabine regimens. We compared RESTRICT measurements with those from a gold-standard method of liquid chromatography tandem mass spectrometry (LC-MS/MS). The ability of RESTRICT to correctly classify DBS tenofovir diphosphate concentrations to established steady-state adherence benchmark concentrations was determined using area under receiver operating characteristic curves (AUCs).</p><p><strong>Results: </strong>The RESTRICT measurements of DBS samples were highly correlated with LC-MS/MS measurements of tenofovir diphosphate from DBS (r = -0.90; P < 0.0001). The RESTRICT assay correctly classified DBS samples as above or below established steady-state adherence benchmark concentrations corresponding to low (AUC = 0.974), moderate (AUC = 0.936) and high (AUC = 0.955) levels of adherence.</p><p><strong>Conclusions: </strong>The enzymatic RESTRICT assay can accurately measure tenofovir diphosphate concentrations in DBS specimens using simple procedures and readily available laboratory equipment, offering accessible objective adherence monitoring for persons receiving tenofovir disoproxil fumarate-based PrEP or ART.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1141-1147"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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