Journal of Antimicrobial Chemotherapy最新文献

{"title":"Assessing the appropriateness of antifungal prescribing: key results from the implementation of a novel audit tool in Australian hospitals.","authors":"A Khanina, N Singh, R James, D C M Kong, M A Slavin, K A Thursky","doi":"10.1093/jac/dkaf044","DOIUrl":"10.1093/jac/dkaf044","url":null,"abstract":"<p><strong>Objectives: </strong>To utilize the Antifungal National Antimicrobial Prescribing Survey (Antifungal NAPS), a novel tool utilizing international consensus metrics for antifungal stewardship, to assess the quality of systemic antifungal prescribing in Australian hospitals, in order to identify quality improvement targets.</p><p><strong>Methods: </strong>Participating hospitals were directed to audit all systemic antifungals or focus on a specific antifungal drug or class. Data entry into the Antifungal NAPS online portal occurred between October 2022 and June 2023. The data collection tool comprised patient details, reasons precluding use of antifungals, prescription details (guideline compliance, appropriateness, and reasons for inappropriate prescribing) and patient outcomes. Descriptive statistics were used to analyse the data.</p><p><strong>Results: </strong>Eleven hospitals contributed data for 516 prescriptions for 438 patients. Of these, 77.1% of prescriptions were appropriate, with the highest appropriateness for prophylactic (189/222; 85.1%), followed by directed (105/130; 80.8%) and empirical therapy (104/164; 63.4%). Fluconazole was the most commonly prescribed agent, which had the lowest rate of appropriateness (132/209; 63.2%). The most common reasons for inappropriate prescribing were no antifungal required (35/105; 33.3%), incorrect dose or frequency (30/105; 28.6%) and incorrect duration (19/105; 18.1%). Compliance with guidelines was 73.6%.</p><p><strong>Conclusions: </strong>This study outlines the successful implementation of the Antifungal NAPS, a standardized electronic audit tool for the assessment of antifungal prescribing quality. Key areas for quality improvement identified were the overuse of empirical fluconazole for urinary tract and intra-abdominal infections, the importance of invasive fungal infection risk assessment to guide prophylaxis prescribing and greater infectious diseases and antifungal stewardship oversight of antifungal prescribing to guide optimal prescribing.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1127-1136"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408060","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":"Type IV PilD mutant stimulates the formation of persister cells in Pseudomonas aeruginosa.","authors":"Huifang Qiu, Weijun Dai","doi":"10.1093/jac/dkaf030","DOIUrl":"10.1093/jac/dkaf030","url":null,"abstract":"<p><strong>Background: </strong>Pseudomonas aeruginosa clinical isolates that lack motility do not express type IV pilin, yet the biological roles of this absence in the infection process remain poorly understood.</p><p><strong>Objectives: </strong>We asked whether the absence of motility in these bacteria is associated with increased antibiotic persistence.</p><p><strong>Methods: </strong>In this study, we analysed type IV PilD protein sequences in the database and conducted antibiotic-tolerant persister cell assays.</p><p><strong>Results: </strong>We found that PilD variants were common in P. aeruginosa clinical isolates. Our results revealed that inactivation of PilD resulted in a significantly higher level of surviving persister cells following ciprofloxacin treatment. This PilD-mediated persistence did not involve previously described mechanisms, such as phenazine pyocyanin, biofilm or stringent response.</p><p><strong>Conclusions: </strong>Our findings connect the non-motility of clinical P. aeruginosa isolates with the survival of persister cells, highlighting the clinical significance for the development of strategies to eradicate P. aeruginosa infections.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1031-1036"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189186","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":"Identification of a mepR mutation associated with tigecycline resistance in a clinical Staphylococcus aureus isolate.","authors":"Hongjie Xing, Likuan Zhang, Chenglong Li, Stefan Schwarz, Dexi Li, Xiang-Dang Du","doi":"10.1093/jac/dkaf034","DOIUrl":"10.1093/jac/dkaf034","url":null,"abstract":"<p><strong>Objectives: </strong>To identify the role and function of mepR variants in conferring resistance to tigecycline in clinical Staphylococcus aureus.</p><p><strong>Methods: </strong>The identification of the mepR and mepA variants in S. aureus DMB26a was performed by whole-genome sequencing and Blast alignment. The effects of the mepRD and mepAD variants of DMB26a on tigecycline susceptibility were evaluated through deletion and complementation analyses, as well as the determination of gene expression levels by RT-qPCR. Minimal inhibitory concentrations (MICs) for DMB26a and its mutants were determined by antimicrobial susceptibility testing.</p><p><strong>Results: </strong>A mepR variant, designated mepRD, and a mepA variant, designated mepAD, were identified in the clinical tigecycline-resistant S. aureus isolate DMB26a, which showed 78.72% and 84.92% amino acid identity to the MepR and MepA proteins of S. aureus NCTC 8325-4, respectively. Our findings revealed that deletion of mepA in the tigecycline-susceptible S. aureus RN4220 did not lead to a decrease in the MIC of tigecycline, and that there was also no change in the tigecycline MIC after the complementation with mepAD. Furthermore, we constructed a mepR + mepA deletion strain of S. aureus RN4220 and complemented it with mepRD + mepAD. In that case, a 4-fold increase in the tigecycline MIC was observed in S. aureus RN4220ΔmepR + mepA-pLI50_mepRD + mepAD compared with S. aureus RN4220ΔmepR + mepA. In addition, the relative expression of mepAD was increased 6-fold under the regulation of mepRD.</p><p><strong>Conclusions: </strong>This study provides the identification of a mepR variant contributing indirectly to tigecycline resistance via mediating increased expression of mepA in a clinical S. aureus isolate.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1059-1066"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364531","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":"Clinical validation of an innovative dried whole-blood spot method to quantify simultaneously vancomycin and creatinine in adult patients.","authors":"M Hassanzai, S Bahmany, H A W van Onzenoort, J van Oldenrijk, B C P Koch, B C M de Winter","doi":"10.1093/jac/dkaf041","DOIUrl":"10.1093/jac/dkaf041","url":null,"abstract":"<p><strong>Background: </strong>A drawback of vancomycin use is the need for therapeutic drug monitoring and renal function monitoring. Traditional blood sampling involves drawing blood through a venepuncture. An alternative method, dried blood spot (DBS) sampling allows for self-sampling at home.</p><p><strong>Objectives: </strong>To clinically validate a DBS method for simultaneous monitoring of vancomycin and creatinine.</p><p><strong>Methods: </strong>Hospitalized adults treated with intravenous vancomycin were included (trial registration NCT05257070). Blood sampling consisted of one venepuncture and one finger prick. Whole-blood DBS samples from patients were obtained by applying one drop of whole blood onto Whatman 903 filtrate paper. Bland-Altman analyses were used to assess the agreement and bias between the two measurements. Patients were asked to state their preferences for one of the two sampling methods.</p><p><strong>Results: </strong>The study involved a final analysis of 39 patient samples for the clinical validation of vancomycin and 46 patient samples for the clinical validation of creatinine. The difference between plasma and DBS concentrations was ≤20% for 77% of the vancomycin samples, the mean bias was -0.1379% (95% limit of agreement -5.899-5.623). The difference between plasma and DBS concentrations was ≤20% for 89% of the creatinine samples, the mean bias was 2.656% (95% limit of agreement -26.16-31.47). Most patients (18 out of 31) preferred a finger prick over a venepuncture and 12 patients indicated no preference.</p><p><strong>Conclusions: </strong>This is the first study that successfully clinically validated a DBS sampling method for simultaneous measurement of vancomycin and creatinine, allowing for direct use in (outpatient) practice.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1097-1107"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449168","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":"Durability of doravirine/dolutegravir dual combination in a multicentre cohort of elderly people with HIV.","authors":"Maria Mazzitelli, Claudia Cozzolino, Cristina Gervasoni, Simone Pagano, Serena Reato, Diego Ripamonti, Laura Comi, Vincenzo Scaglione, Daniele Mengato, Giuseppe Formica, Filippo Lagi, Antonio Cascio, Marcello Trizzino, Valentina Iannone, Damiano Farinacci, Annamaria Cattelan","doi":"10.1093/jac/dkaf039","DOIUrl":"10.1093/jac/dkaf039","url":null,"abstract":"<p><strong>Background: </strong>Even though the doravirine/dolutegravir combination is not mentioned by guidelines, real-life data has begun to emerge on its use. We aimed to describe the durability of doravirine/dolutegravir in a multicentre Italian cohort of elderly people with HIV (EPWH).</p><p><strong>Methods: </strong>We included all EPWH who ever started the doravirine/dolutegravir combination in six Italian centres and were followed up until treatment discontinuation (TD) for any reason (virological failure, death, treatment interruption for other reasons) on 31 March 2024. Descriptive statistics were used to describe the study population; Kaplan-Meier curves and Cox regression analyses were used to estimate incidence and associated predictors of time to TD.</p><p><strong>Results: </strong>We included 157 people; 61.1% were male, the median age was 59 years (IQR: 55-64), 75.2% had multimorbidity, 38.9% were on polypharmacy, and 91.1% had HIV-RNA of <50 copies/mL. No genotype resistance test was available for 19.4% of people who started doravirine/dolutegravir. The main reasons for starting doravirine/dolutegravir were high cardiovascular risk (51.6%), simplification (52.9%) and drug-drug interactions (25.5%). During a median follow-up of 27.85 (IQR: 22.92-31.79) months, 8 (5.1%) participants experienced TD (2 toxicities, 2 virological failures, 2 switches to long-acting drugs, 1 death and 1 transferred). The incidence of TD was 2.27 per 100 person-years of follow-up. Multivariable Cox regression analyses did not show any factors as predictors of TD.</p><p><strong>Conclusions: </strong>In this multicentre cohort of EPWH with clinical complexity, the doravirine/dolutegravir combination showed good durability over time. TD probability was very low, and no significant factors seem to predict it, likely due to the limited number and heterogeneity of cases of TD.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1089-1096"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390872","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":"Relationship between posaconazole concentrations and clinical outcomes in paediatric cancer and haematopoietic stem cell transplant recipients.","authors":"Heather Weerdenburg, Hannah Walker, Gabrielle M Haeusler, Theresa Cole, Nigel Curtis, Stephen Duffull, Amanda Gwee","doi":"10.1093/jac/dkae473","DOIUrl":"10.1093/jac/dkae473","url":null,"abstract":"<p><strong>Background: </strong>Posaconazole is used to prevent and treat invasive fungal infections (IFIs) in immunocompromised children, including those undergoing cancer treatment or HSCT. Despite differences in pharmacokinetics and IFI epidemiology between children and adults, therapeutic targets established in adult studies are often applied to children.</p><p><strong>Objectives: </strong>This systematic review evaluated the correlation between serum posaconazole concentrations and clinical outcomes of IFI prophylaxis and treatment in children with malignancies or HSCT recipients.</p><p><strong>Methods: </strong>Four databases (Cochrane, Embase, MEDLINE and PubMed) were searched for studies involving children (≤18 years old) receiving cancer treatment or HSCT that reported posaconazole serum concentrations and treatment outcomes. Animal studies, those primarily in adult (>18 years old) populations, non-malignant conditions (excluding HSCT), case reports, letters, editorials, conference abstracts and narrative reviews were excluded. Bias was assessed using the Newcastle-Ottawa scale.</p><p><strong>Results: </strong>Nineteen studies were included: 12 reported outcomes of posaconazole prophylaxis; two of treatment; and five of both. For prophylaxis, breakthrough IFIs occurred in 1%-12% of children. All but one occurred with serum concentrations of ≤0.7 mg/L. For treatment, no clear association was observed between a trough concentration of >1.0 mg/L and treatment efficacy, with poor outcomes reported for serum concentrations ranging between 0.2 and 4.8 mg/L. Overall, quality of evidence was poor (medium to high risk of bias for 18 papers, low risk for 1 paper) and there was variation in IFI definitions across studies.</p><p><strong>Conclusions: </strong>This review supports current recommendations for posaconazole prophylaxis in paediatric oncology and HSCT recipients. The absence of a clear correlation found between serum trough concentrations and treatment efficacy highlights the need for further studies to determine optimal therapeutic targets for treatment.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"897-907"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556789","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":"Early clinical experience using tecovirimat during the 2022 mpox epidemic in Toronto underscores ongoing clinical equipoise and the need for randomized trials.","authors":"Shreya S Khera, Sharmistha Mishra, Oscar Javier Pico Espinosa, Kevin Gough, Charlie Tan, Sharon Walmsley, Alice Zhabokritsky, Malika Sharma, Adrienne K Chan, Jerome A Leis, Myo Minn Oo, Darrell H S Tan","doi":"10.1093/jac/dkaf010","DOIUrl":"10.1093/jac/dkaf010","url":null,"abstract":"<p><strong>Background: </strong>Tecovirimat is an antiviral drug that was used compassionately for treating mpox in high-income settings during the 2022 global outbreak. Randomized controlled trials of its efficacy have not yet been completed.</p><p><strong>Objectives: </strong>To describe medication adherence, tolerability and clinical outcomes of adults receiving open-label tecovirimat for mpox infection.</p><p><strong>Methods: </strong>We conducted a prospective observational study and a retrospective case series of adults with mpox cared for at three academic hospitals in Toronto, Canada, between May and August 2022. We present a descriptive analysis of those prescribed oral tecovirimat 600 mg twice daily for 14 days for the management of severe manifestations.</p><p><strong>Results: </strong>Of 69 consenting participants, all were cisgender men, of whom 60 (87%) identified as gay, and 6 (9%) as bisexual. Nearly half (46%) were living with HIV, with a median (IQR) CD4 count of 468 (328-678) cells/mm3, among whom plasma HIV RNA was <20 copies/mL in 29 (91%) participants. One-third (33%) of participants received tecovirimat during the course of their illness. All participants experienced a decline in number of symptoms over time, but three treated participants initially experienced worsening symptoms despite therapy. Self-reported adherence to tecovirimat was excellent and tolerability was good.</p><p><strong>Conclusions: </strong>Our experience prescribing tecovirimat for mpox suggests it is safe and well tolerated, but the evolution of symptoms in some tecovirimat-treated patients underscores the ongoing uncertainty regarding its efficacy. In the context of considerable community demand for the drug, efforts should be made to connect mpox patients to rigorous randomized controlled trials, given this ongoing clinical equipoise.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"935-940"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441014","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":"Prevalence of antifungal allergies in the general population.","authors":"Meron W Shiferaw, Monica A Donnelley, George R Thompson","doi":"10.1093/jac/dkaf037","DOIUrl":"10.1093/jac/dkaf037","url":null,"abstract":"<p><strong>Objectives: </strong>Invasive fungal infections are increasing in frequency and are associated with high patient morbidity and mortality. The use of antifungal therapy is thus also increasing, and patients reporting hypersensitivity or allergic reactions to the limited antifungal agents currently available complicates management. There are no prior studies defining the incidence of antifungal allergies reported by patients.</p><p><strong>Methods: </strong>A multicentre retrospective cohort review of all patient encounters at five large academic centres during 2023 was conducted. The primary outcome of this study was to find the prevalence of reported antifungal allergy across the University of California Health System, and secondarily determine the incidence of antifungal allergies among patients with documented administration of antifungal agent.</p><p><strong>Results: </strong>A total of 1 704 176 patients were included and 2602 patients exhibited a documented antifungal allergy. Prevalences of antifungal allergies were: fluconazole 1591 (0.093%), general antifungal allergy 395 (0.023%), triazole 361 (0.021%), itraconazole 145 (0.008%), amphotericin 110 (0.006%) and flucytosine <10 (0.001%). In the secondary outcome (incidence), 9829 patients received an antifungal agent and 298 reported an antifungal allergy (2.98%).</p><p><strong>Conclusions: </strong>Increasing age and use of antifungal therapy are associated with antifungal allergy prevalence. Antifungal allergy rates (prevalence and incidence) are also comparable to the rates reported for antibacterial agents and are highest with fluconazole.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1080-1083"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441016","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":"High-level cefiderocol and ceftazidime/avibactam resistance in KPC-producing Klebsiella pneumoniae associated with mutations in KPC and the sensor histidine kinase EnvZ.","authors":"Jacqueline Findlay, Gabriele Bianco, Matteo Boattini, Patrice Nordmann","doi":"10.1093/jac/dkaf048","DOIUrl":"10.1093/jac/dkaf048","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1155-1157"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449244","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":"Identification of the czc metal efflux operon on a new plasmid type in a Pseudomonas aeruginosa clinical isolate belonging to ST357 O11.","authors":"Adam Valcek, Diana Isabela Costescu Strachinaru, Patrick Soentjens, Anke Stoefs, Charles Van der Henst","doi":"10.1093/jac/dkaf058","DOIUrl":"10.1093/jac/dkaf058","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1158-1160"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556843","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}