Journal of Antimicrobial Chemotherapy最新文献

{"title":"The optrA, cfr(D) and vanA genes are co-located on linear plasmids in linezolid- and vancomycin-resistant enterococcal clinical isolates in Italy.","authors":"Marzia Cinthi, Sonia Nina Coccitto, Serena Simoni, Giovanni Gherardi, Anna Teresa Palamara, Silvia Di Lodovico, Mara Di Giulio, Xiang-Dang Du, Carla Vignaroli, Andrea Brenciani, Eleonora Giovanetti","doi":"10.1093/jac/dkaf082","DOIUrl":"https://doi.org/10.1093/jac/dkaf082","url":null,"abstract":"<p><strong>Objectives: </strong>To characterize the optrA-, cfr(D)- and vanA-carrying linear plasmids detected in three MDR enterococcal clinical isolates.</p><p><strong>Methods: </strong>Enterococcus faecium (868), E. faecium (1001) and Enterococcus faecalis (2048), which were linezolid- and vancomycin-resistant due to the presence of optrA, cfr(D) and vanA genes, were tested for their susceptibility to several antibiotics. Characterization of the genetic elements carrying antibiotic resistance genes and ST determination were achieved using WGS data. The plasmid topology was evaluated by S1-PFGE. Resistance gene transferability was assessed by filter-mating experiments.</p><p><strong>Results: </strong>The linezolid- and vancomycin-resistant enterococci also showed resistance to tedizolid, chloramphenicol, tetracycline, erythromycin, ampicillin and levofloxacin. Both E. faecium 868 and E. faecium 1001 belonged to ST80 (included in clade A1), whereas E. faecalis 2048 was associated with ST6. WGS analysis revealed a plasmid co-localization of the optrA, cfr(D) and vanA genes. optrA was carried by Tn6674-like or Tn7695-like transposons; cfr(D) was associated with a truncated guaA gene, both flanked by IS1216 with opposite polarity; vanA was found on a Tn1546-like transposon containing IS1542 and IS1251 transposases. PFGE of S1 nuclease-treated and untreated DNAs displayed the linear topology of optrA-, cfr(D)- and vanA-harbouring plasmids. Only E. faecium 868 was able to transfer linezolid and vancomycin genes to an enterococcal recipient.</p><p><strong>Conclusions: </strong>To the best of our knowledge this is the first report on the occurrence of a linear plasmid in E. faecalis. Linear plasmids can play a key role in the spread of oxazolidinone and glycopeptide resistance with serious consequences for public health.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648698","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":"Monitoring strategies and vancomycin-associated acute kidney injury in patients treated at home.","authors":"Wendy Morimoto, Mubarika Alavi, Cynthia I Campbell, Meredith Silverman","doi":"10.1093/jac/dkaf086","DOIUrl":"https://doi.org/10.1093/jac/dkaf086","url":null,"abstract":"<p><strong>Objectives: </strong>The 2020 vancomycin consensus guidelines recommend AUC-guided dosing over trough-based dosing to decrease nephrotoxicity. This study was performed to add data comparing these dosing methods in the outpatient setting.</p><p><strong>Methods: </strong>This retrospective cohort study compared trough-guided versus AUC-guided dosing in patients receiving vancomycin through two home infusion pharmacies (HIPs). Multivariate analysis was performed to report adjusted relative risks, adjusting for patient demographics and clinical characteristics. Eligible patients were ≥18 years old, had an absolute neutrophil count of ≥1000 cells/mm3, a baseline serum creatinine of <2.0 mg/dL at HIP intake, and ≥7 days of IV vancomycin at home. Primary outcome was rate of acute kidney injury (AKI) events, defined as the number of AKI events per treatment days. Secondary outcomes were rate of 30 day hospital readmission and number of HIP interventions (vancomycin dose changes).</p><p><strong>Results: </strong>Six hundred and sixty patients were included (303 trough, 357 AUC). The mean number of AKI events was 0.84 per treatment day for trough-guided versus 0.63 for AUC-guided dosing (P = 0.11). In adjusted models, there were no significant associations between the exposure and AKI events [relative risk (RR) = 0.8, 95% CI 0.5-1.2, P = 0.26], 30 day hospital readmissions (RR 1.0, 95% CI 0.8-1.3, P = 0.71) or number of pharmacy interventions (RR = 1.0, 95% CI 0.9-1.2, P = 0.67).</p><p><strong>Conclusions: </strong>There was no significant difference in AKI rates among patients receiving vancomycin via trough- or AUC-guided monitoring and dosing through a HIP. Further evaluation is needed to determine how to improve AKI rates using AUC-guided monitoring and dosing among patients receiving vancomycin therapy at home.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648680","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":"Antipseudomonal cephalosporins versus piperacillin/tazobactam or carbapenems for the definitive antibiotic treatment of Pseudomonas aeruginosa bacteraemia: new kids on the ICU block?","authors":"Davide Fiore Bavaro, Giuseppe Accurso, Silvia Corcione, Antonio Vena, Michela Schenone, Lucia Diella, Teresa Fasciana, Maddalena Giannella, Daniele Roberto Giacobbe, Simone Mornese Pinna, Renato Pascale, Francesca Giovannenze, Nicholas Geremia, Andrea Marino, Pierluigi Viale, Francesco Giuseppe De Rosa, Matteo Bassetti, Michele Bartoletti","doi":"10.1093/jac/dkaf080","DOIUrl":"https://doi.org/10.1093/jac/dkaf080","url":null,"abstract":"<p><strong>Background: </strong>Pseudomonas aeruginosa bloodstream infections (Pa-BSIs) are still a major cause of mortality in ICUs, posing many treatment uncertainties.</p><p><strong>Methods: </strong>This multicentre, retrospective study analysed data from 14 Italian hospitals, including all consecutive adults developing Pa-BSI in ICU during 2021-22 and treated with antibiotics for at least 48 h. The primary aim was to identify predictors of 30 day mortality using Cox regression. Results were adjusted with inverse probability of treatment weighting (IPTW) and for immortal time bias.</p><p><strong>Results: </strong>Overall, 170 patients were included. High-risk BSI (source: lung, intra-abdominal, CNS) occurred in 118 (69%) patients, and 54 (32%) had septic shock. In 37 (22%), 73 (43%), 12 (7%) and 48 (28%) the definitive backbone therapy was piperacillin/tazobactam, carbapenems, colistin or new antipseudomonal cephalosporins (ceftolozane/tazobactam, n = 20; ceftazidime/avibactam, n = 22; cefiderocol, n = 6), respectively. Moreover, 58 (34%) received a second drug as combination therapy. The incidence of 30 day all-cause mortality was 27.6% (47 patients). By Cox regression, Charlson comorbidity index, neutropenia, septic shock and high-risk BSI were independent predictors of 30 day mortality, while previous colonization by P. aeruginosa, use of antipseudomonal cephalosporins as definitive treatment, and combination therapy were shown to be protective. However, after IPTW adjustment, only the protective effect of antipseudomonal cephalosporins was confirmed (adjusted HR = 0.27, 95% CI = 0.10-0.69), but not for combination therapy. Hence, the treatment effect was calculated: antipseudomonal cephalosporins significantly reduced mortality risk [-17% (95% CI = -4% to -30%)], while combination therapy was beneficial only in the case of septic shock [-66% (95% CI = -44% to -88%].</p><p><strong>Conclusions: </strong>In ICU, antipseudomonal cephalosporins may be the preferred target therapy for the treatment of Pa-BSI; in addition, initial combination therapy may be protective in the case of septic shock.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634040","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":"Refractory versus resistant invasive aspergillosis.","authors":"Maiken Cavling Arendrup, Catherine Cordonnier","doi":"10.1093/jac/dkaf003","DOIUrl":"10.1093/jac/dkaf003","url":null,"abstract":"<p><p>Despite notable progress, the management of invasive aspergillosis (IA) remains challenging and treatment failures are common. The final patient outcome is subject to multiple factors including the host (the severity of the underlying conditions), the fungus (the virulence and susceptibility pattern of the Aspergillus species involved), and the therapy (the timing related to severity of infection and choice of therapy-dose, efficacy, cidal versus static, toxicity and interaction). Consequently, assessment of failure is complex yet crucial in order to ensure appropriate management. Refractoriness in absence of drug resistance may reflect severity of the underlying disease/infection at the time of initiation of therapy prolonging time to response. It may also reflect a suboptimal antifungal drug exposure due to poor compliance, inappropriate dosing or increased drug metabolism, or it may reflect 'pseudo' failure due to worsening of imaging due to recovery of neutrophils. Refractoriness may also be related to inherent drug resistance in various Aspergillus species or acquired resistance in a normally susceptible species. The latter scenario is mostly encountered in A. fumigatus, where azole resistance is increasing and includes azole-naive patients due to resistance related to azole fungicide use in agriculture and horticulture. Although diagnostics and resistance detection have been greatly improved, the time to resistance reporting is often still suboptimal, which calls for close assessment and potentially management changes even before the susceptibility is known. In this article we address the various definitions and approaches to assessment and management of clinical refractoriness/failure in the setting of proven and probable IA.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"80 Supplement_1","pages":"i9-i16"},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630489","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}

{"title":"Diagnosis and management of refractory and rare moulds.","authors":"Jame Hurley, Esteban Martinez","doi":"10.1093/jac/dkaf031","DOIUrl":"10.1093/jac/dkaf031","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"80 Supplement_1","pages":"i1"},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630391","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}

{"title":"Applying quality improvement methods to reduce antibiotic use in neonates: a systematic review and meta-analysis.","authors":"Bo Wang, Na Wang, Zhangbin Yu, Jia Zhang","doi":"10.1093/jac/dkaf078","DOIUrl":"https://doi.org/10.1093/jac/dkaf078","url":null,"abstract":"<p><strong>Background: </strong>This study aims to explore effective interventions and observation indicators for reducing antibiotic use in neonates through quality improvement (QI) methods, while quantitatively analysing whether these methods increase the risk of neonatal mortality and serious adverse outcomes.</p><p><strong>Methods: </strong>By 27 August 2024, we reviewed all pertinent literature. A descriptive statistical analysis was conducted on all intervention measures, outcome indicators, process indicators, and balance indicators. The group utilizing QI interventions was designated as the intervention group, with the baseline period serving as the control group. The mortality rates and incidence of serious adverse outcomes were treated as dichotomous variables. The risk ratio (RR) and 95% CIs were effect indicators.</p><p><strong>Results: </strong>In total, 57 studies published between 2016 and 2024 were included. All studies were uncontrolled before-and-after studies. The most studied country was the United States of America. From these 57 studies, 27 effective intervention measures were identified, and all observation indicators and main results were presented in tabular form. According to the meta-analysis, the mortality rate in the intervention group decreased by 30% compared with the control group (RR = 0.7; 95% CI: 0.604-0.81; P < 0.001), while there was no statistically significant difference in the risk of serious adverse outcomes between the two groups.</p><p><strong>Conclusions: </strong>QI methods can safely and effectively reduce the use of antibiotics in neonates, highlighting their potential for clinical applications.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624582","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":"Diagnosis and management of invasive fungal infections due to non-Aspergillus moulds.","authors":"C Orla Morrissey","doi":"10.1093/jac/dkaf005","DOIUrl":"10.1093/jac/dkaf005","url":null,"abstract":"<p><p>Invasive fungal infection (IFI) due to moulds other than Aspergillus are a significant cause of morbidity and mortality. Non-Aspergillus mould (NAM) infections appear to be on the increase due to an ever-expanding population of immunocompromised hosts. In this review, Mucorales, Scedosporium species, Lomentospora prolificans and Fusarium species are examined in detail, and the microbiology, risk factors, diagnosis and treatment of emerging NAMs such as Paecilomyces variotti, Purpureocillium lilacinum and Rasamsonia are summarized. The challenges in diagnosis are emphasized and the emerging importance of molecular methods is discussed. Treatment of IFI due to NAMs is a multi-pronged and multi-disciplinary approach. Surgery, correction of underlying risk factors, and augmentation of the host immune response are as important as antifungal therapy. Many of these NAMs are intrinsically resistant to the currently licensed antifungal agents, so selection of therapy needs to be guided by susceptibility testing. There are new antifungal agents in development, and these have the potential to improve the efficacy and safety of antifungal treatment in the future. Ongoing research is required to fully delineate the epidemiology of NAM infections, and to develop better diagnostic tools and treatments so that outcomes from these infections can continue to improve.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"80 Supplement_1","pages":"i17-i39"},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630456","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}

{"title":"Clinical aspects and recent advances in fungal diseases impacting human health.","authors":"Livio Pagano, Omar Marín Fernández","doi":"10.1093/jac/dkaf004","DOIUrl":"10.1093/jac/dkaf004","url":null,"abstract":"<p><p>Fungal diseases are of growing clinical concern in human medicine as the result of changes in the epidemiology, diversity in clinical presentation, emergence of new pathogens, difficulties in diagnosis and increasing resistance to antifungals of current available classes. There is a need for high disease awareness among the public and healthcare physicians, improvement in diagnostic methods and the development of drugs from new therapeutic classes with an improved resistance profile. In this article, we will explore some key aspects of fungal diseases in humans and provide a general overview of this important topic.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"80 Supplement_1","pages":"i2-i8"},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630454","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}

{"title":"Coccidioidomycosis: a growing global concern.","authors":"Fariba M Donovan, Omar Marín Fernández, Gurjinder Bains, Lisa DiPompo","doi":"10.1093/jac/dkaf002","DOIUrl":"10.1093/jac/dkaf002","url":null,"abstract":"<p><p>Coccidioidomycosis (CM) has been a recognized disease for about 130 years. The organisms (Coccidioides spp. fungi) inhabit desert soil in the southwestern USA, Mexico, and parts of Central and South America. Natural events such as dust storms, wildfires or outdoor activities including construction and gardening can disrupt the fungal arthroconidia, which easily become airborne and inhaled by the host. Approximately 60% of those exposed to arthroconidia are asymptomatic and do not require medical attention, but 30% show signs of pulmonary infection with symptoms ranging from a flu-like illness to pneumonia. In 5%-10% of cases serious or disseminated disease develops, which requires prompt diagnosis and management. About 1%-3% of infections disseminate to the CNS and if not appropriately treated are often fatal. There is an urgent need for improved diagnostics and treatments.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"80 Supplement_1","pages":"i40-i49"},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630455","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}

{"title":"Pharmacodynamic assessment of apramycin against Mycobacterium abscessus in a hollow fibre infection model.","authors":"Nidhi Singh, Bikash Dangi, Jeremy J Johnson, Arnold Louie, Arunkumar Karunanidhi, Brooke N Curry, Satoshi Mitarai, Charles L Daley, Sven N Hobbie, Zackery P Bulman","doi":"10.1093/jac/dkaf073","DOIUrl":"https://doi.org/10.1093/jac/dkaf073","url":null,"abstract":"<p><strong>Background: </strong>Mycobacterium abscessus is an important cause of pulmonary infections, particularly among people with cystic fibrosis. Current treatment options for M. abscessus are suboptimal. Apramycin is a promising alternative aminoglycoside for M. abscessus, in part due to its ability to avoid intrinsic aminoglycoside-modifying enzymes in this pathogen.</p><p><strong>Objectives: </strong>Define the pharmacodynamic activity of apramycin doses against M. abscessus.</p><p><strong>Methods: </strong>Apramycin and amikacin pharmacodynamics were assessed against two amikacin-susceptible M. abscessus subsp. abscessus isolates (ATCC 19977 and NR-44261) using a 14-day hollow fibre infection model (HFIM). Viable bacterial counts were determined during exposure to amikacin (15-20 mg/kg q24h) and 3 fractionated doses of apramycin (15 mg/kg q12h, 30 mg/kg q24h, 60 mg/kg q48h) using pharmacokinetic profiles predicted in epithelial lining fluid.</p><p><strong>Results: </strong>Against ATCC 19977, apramycin activity exceeded that of amikacin, with maximum bacterial reductions between 1.51 and 2.18 log10 cfu/mL for the different doses. Apramycin 15 mg/kg q12h displayed slightly better killing compared with the other apramycin dosing regimens between 96 and 144h before regrowth occurred. NR-44261 was not inhibited by amikacin and the activity of apramycin against this isolate was similar between the three doses (∼0.5 log10 cfu/mL reductions). After 14 days of exposure to apramycin monotherapy, ATCC 19977 and NR-44261 became apramycin resistant with MICs of >32 mg/L.</p><p><strong>Conclusions: </strong>Apramycin exhibited greater pharmacodynamic activity than amikacin against amikacin-susceptible M. abscessus isolates and may be a promising therapy for this pathogen. However, antibiotic combination strategies to minimize apramycin resistance from emerging may be necessary.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624585","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}