JAC-Antimicrobial Resistance最新文献

{"title":"Antimicrobial stewardship markers and healthcare-associated pneumonia threshold criteria in UK hospitals: analysis of the MicroGuide^Tm application.","authors":"Luke S P Moore, Ioannis Baltas, James Amos, Mineli Cooray, Stephen Hughes, Rachel Freeman, Tom Ashfield","doi":"10.1093/jacamr/dlae058","DOIUrl":"https://doi.org/10.1093/jacamr/dlae058","url":null,"abstract":"<p><strong>Background: </strong>To address antimicrobial resistance, antimicrobial stewardship (AMS) principles must be implemented and adhered to. Clinical decision aids such as the MicroGuide^TM app are an important part of these efforts. We sought to evaluate the consistency of core AMS information and the diversity of classification thresholds for healthcare-associated pneumonia (HAP) in the MicroGuide app.</p><p><strong>Methods: </strong>Guidelines in the MicroGuide app were extracted and analysed for content related to AMS and HAP. Guidelines were characterized according to HAP naming classification; community-acquired pneumonia (CAP) classifications were analysed to serve as a comparator group.</p><p><strong>Results: </strong>In total, 115 trusts (119 hospitals) were included. Nearly all hospitals had developed MicroGuide sections on AMS (<i>n</i> = 112/119, 94%) and sepsis management (<i>n</i> = 117/119, 98%). Other AMS sections were outpatient parenteral antimicrobial therapy (47%), antifungal stewardship (70%), critical care (23%) and IV to oral switch therapy (83%). Only 9% of hospitals included guidance on the maximum six key AMS sections identified. HAP definitions varied widely across hospitals with some classifying by time to onset and some classifying by severity or complexity. The largest proportion of HAP guidelines based classification on severity/complexity (<i>n</i> = 69/119, 58%). By contrast, definitions in CAP guidelines were uniform.</p><p><strong>Conclusions: </strong>The high heterogeneity in HAP classification identified suggests inconsistency of practice in identifying thresholds for HAP in the UK. This complicates HAP management and AMS practices. To address HAP in alignment with AMS principles, a comprehensive strategy that prioritizes uniform clinical definitions and thresholds should be developed.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"6 2","pages":"dlae058"},"PeriodicalIF":3.4,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11022069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selection of proxy indicators estimating the appropriateness of antibiotic prescriptions in general practice: a national consensus procedure in France.","authors":"Maïa Simon, Aurélie Bocquier, Ouarda Pereira, Alexandre Charmillon, Damien Gonthier, Florence Lieutier Colas, Camille Vallance, Adeline Welter, Céline Pulcini, Nathalie Thilly","doi":"10.1093/jacamr/dlae059","DOIUrl":"https://doi.org/10.1093/jacamr/dlae059","url":null,"abstract":"<p><strong>Background: </strong>GPs are responsible for more than 70% of outpatient antibiotic prescriptions in France. Metrics are important antibiotic stewardship tools that can be used to set targets for improvement and to give feedback to professionals and stakeholders.</p><p><strong>Objectives: </strong>The primary objective of the present study was to select a set of proxy indicators (PIs) based on 10 previously developed PIs, to estimate the appropriateness of antibiotic prescriptions by GPs. The secondary objective was to evaluate the clinimetric properties of the selected PIs.</p><p><strong>Methods: </strong>A RAND-modified Delphi consensus procedure was conducted with a multidisciplinary panel of stakeholders. This procedure consisted of two successive online surveys with a consensus meeting in between. Clinimetric properties (measurability, applicability and potential room for improvement) were evaluated for the PIs selected through the consensus procedure, using 2022 Regional Health Insurance data.</p><p><strong>Results: </strong>Seventeen experts participated in the first-round survey and 14 in the second-round. A final set of 12 PIs was selected. Among the 10 initial PIs, 3 were selected without modification and 7 were modified and selected. Moreover, two newly suggested PIs were selected. Ten of the 12 PIs presented good clinimetric properties.</p><p><strong>Conclusions: </strong>The 12 selected PIs cover the main situations responsible for inappropriate and unnecessary use of antibiotics in general practice. These PIs, easily calculable using routinely collected health insurance reimbursement data, might be used to give feedback to prescribers and stakeholders and help improve antibiotic prescriptions in primary care.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"6 2","pages":"dlae059"},"PeriodicalIF":3.4,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11022070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of carbapenem MIC for NDM-producing Enterobacterales by different AST methods.","authors":"Alfred Lok Hang Lee, Eddie Chi Man Leung, Viola Chi Ying Chow","doi":"10.1093/jacamr/dlae028","DOIUrl":"https://doi.org/10.1093/jacamr/dlae028","url":null,"abstract":"<p><strong>Introduction: </strong>This study compared the performance of MIC test strip (ETEST), automated AST card (Vitek 2) and broth microdilution (BMD) in determining carbapenem susceptibility and MIC values of NDM-producing Enterobacterales.</p><p><strong>Methods: </strong>NDM-producing Enterobacterales recovered from clinical specimens were included. The presence of <i>bla</i>_NDM was confirmed by PCR. Identification of bacterial isolates was done by MALDI-TOF. Phenotypic susceptibility to three carbapenems (ertapenem, imipenem and meropenem) was tested by BMD, ETEST and Vitek 2. MIC values were interpreted in accordance with CLSI M100 (2022 edition). Using BMD as the reference standard, the essential agreement (EA), categorical agreement (CA), very major error (VME) and major error (ME) rates were evaluated.</p><p><strong>Results: </strong>Forty-seven NDM-producing Enterobacterales isolates were included, 44 of which were <i>Escherichia coli</i>. The EA of Vitek 2 was 97.9% for ertapenem, 25.5% for meropenem and 42.6% for imipenem. Using Vitek 2, there were 0% VMEs across all three carbapenems tested. The EA of ETEST was 53.2% for ertapenem, 55.3% for imipenem and 36.2% for meropenem. The rates of VMEs for ETEST were high too (ertapenem 8.5%, meropenem 36.2%, imipenem 26.1%). The MIC values obtained from Vitek 2 were consistently higher than those from BMD, while MICs from ETEST were consistently lower than those from BMD.</p><p><strong>Conclusions: </strong>The VME rate for ETEST was unacceptably high when BMD was used as the standard for comparison. Vitek 2 had acceptable EA and CA for ertapenem when BMD was used as the standard for comparison. For meropenem and imipenem, neither of the methods (ETEST, Vitek 2) showed acceptable EA and CA when compared with BMD.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"6 2","pages":"dlae028"},"PeriodicalIF":3.4,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11057202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the stability of ceftazidime/avibactam in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy utilizing a national stability protocol framework.","authors":"Saiyuri Naicker, Jason A Roberts, Hayoung Won, Steven C Wallis, Sean Unwin, Conor Jamieson, Tim Hills, Mark Gilchrist, Mark Santillo, R Andrew Seaton, Felicity Drummond, Fekade B Sime","doi":"10.1093/jacamr/dlae056","DOIUrl":"https://doi.org/10.1093/jacamr/dlae056","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the stability of ceftazidime/avibactam in elastomeric infusers, utilizing the UK's Yellow Cover Document (YCD) stability testing framework, in conditions representative of OPAT practice.</p><p><strong>Methods: </strong>Ceftazidime/avibactam was reconstituted with sodium chloride 0.9% (w/v) in two elastomeric infusers at concentrations (dose) levels of 1500/375, 3000/750 and 6000 mg/1500 mg in 240 mL. The infusers were exposed to a fridge storage (2°C-8°C) for 14 days followed by 24 h in-use temperature (32°C).</p><p><strong>Results: </strong>After 14 days of fridge storage and subsequent 24 h exposure to 32°C, mean ± SD of ceftazidime percent remaining was 75.5% ± 1.8%, 79.9% ± 1.1%, 82.4% ± 0.6%, for Easypump, and 81.7% ± 1.2%, 82.5% ± 0.5%, 85.4% ± 1.1% for Dosi-Fuser devices at the high, intermediate and low doses tested, respectively. For avibactam, mean ± SD percent remaining was 83.2% ± 1.8%, 87.4% ± 2.0%, 93.1% ± 0.9% for Easypump, and 85.1% ± 2.0%, 86.7% ± 0.1%, 92.5% ± 0.1% for Dosi-Fuser devices. The cumulative amount of pyridine generated in the devices ranged from 10.4 mg at low dose to 76.9 mg at high dose. Regression-based simulation showed that the degradation of both ceftazidime and avibactam was <10% for at least 12 h of the running phase, if stored in a fridge for not more than 72 h prior to in-use temperature exposure.</p><p><strong>Conclusions: </strong>Whilst not meeting the strict UK YCD criteria for ≤5% degradation, ceftazidime/avibactam may be acceptable to administer as a continuous 12 hourly infusion in those territories where degradation of ≤10% is deemed acceptable.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"6 2","pages":"dlae056"},"PeriodicalIF":3.4,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10995722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High prevalence of ceftriaxone-resistant and XDR <i>Neisseria gonorrhoeae</i> in several cities of Cambodia, 2022-23: WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP).","authors":"V Ouk, L Say Heng, M Virak, S Deng, M M Lahra, R Frankson, K Kreisel, R McDonald, M Escher, M Unemo, T Wi, I Maatouk","doi":"10.1093/jacamr/dlae053","DOIUrl":"10.1093/jacamr/dlae053","url":null,"abstract":"<p><strong>Objectives: </strong>Antimicrobial resistance (AMR) in <i>Neisseria gonorrhoeae</i> is a global public health concern. Ceftriaxone is the last effective and recommended option for empirical gonorrhoea therapy worldwide, but several ceftriaxone-resistant cases linked to Asia have been reported internationally. During January 2022-June 2023, the WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) investigated <i>N. gonorrhoeae</i> AMR and epidemiological factors in patients from 10 clinical sentinel sites in Cambodia.</p><p><strong>Methods: </strong>Urethral swabs from males with urethral discharge were cultured. ETEST determined the MIC of five antimicrobials, and EGASP MIC alert values and EUCAST breakpoints were used. EGASP demographic, behavioural and clinical variables were collected using a standardized questionnaire.</p><p><strong>Results: </strong>From 437 male patients, 306 had positive <i>N. gonorrhoeae</i> cultures, AMR testing and complete epidemiological data. Resistance to ceftriaxone, cefixime, azithromycin and ciprofloxacin was 15.4%, 43.1%, 14.4% and 97.1%, respectively. Nineteen (6.2%) isolates were resistant to all four antimicrobials and, accordingly, categorized as XDR <i>N. gonorrhoeae</i>. These XDR isolates were collected from 7 of the 10 sentinel sites. No EGASP MIC alert values for gentamicin were reported. The nationally recommended cefixime 400 mg plus azithromycin 1 g (65.4%) or ceftriaxone 1 g plus azithromycin 1 g (34.6%) was used for treatment.</p><p><strong>Conclusions: </strong>A high prevalence of ceftriaxone-resistant, MDR and XDR <i>N. gonorrhoeae</i> in several cities of Cambodia were found during 2022-23 in WHO EGASP. This necessitates expanded <i>N. gonorrhoeae</i> AMR surveillance, revision of the nationally recommended gonorrhoea treatment, mandatory test of cure, enhanced sexual contact notification, and ultimately novel antimicrobials for the treatment of gonorrhoea.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"6 2","pages":"dlae053"},"PeriodicalIF":3.7,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10993901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Individual and institutional predisposing factors of MRSA surgical site infection and outcomes-a retrospective case-control-study in 14 European high-volume surgical centres.","authors":"Jule Rutz, Jan-Hendrik Naendrup, Caroline Bruns, Annika Y Classen, Jon Salmanton-García, Harald Seifert, Rosanne Sprute, Jannik Stemler, Sarah V Walker, Oliver A Cornely, Blasius J Liss, Sibylle C Mellinghoff","doi":"10.1093/jacamr/dlae046","DOIUrl":"https://doi.org/10.1093/jacamr/dlae046","url":null,"abstract":"<p><strong>Objectives: </strong>To assess incidence rates of surgical site infections (SSI) by MRSA and to determine related factors and clinical outcome compared to MSSA, including country-specific, institutional and patient determinants.</p><p><strong>Patients and methods: </strong>We performed a subgroup analysis of the Europe-wide SALT (NCT03353532) study population with MRSA SSI from 14 centres in France, Germany, Italy, Spain and the UK.</p><p><strong>Results: </strong>An overall MRSA SSI incidence of 0.06% (<i>n</i> = 104) was found in 178 903 patients undergoing invasive surgery in 2016. Frequently observed comorbidities were chronic cardiovascular disease, diabetes and solid tumours. Compared to the overall MRSA SSI incidence, incidence rates were significantly higher in Spain (58 of 67 934 cases) and lower in Germany (16 of 46 443 cases; both <i>P </i>< 0.05). Centres with antibiotic stewardship (ABS) and infectious disease (ID) consultation programmes (<i>n</i> = 3/14) had lower MRSA rates (17 of 43 556 cases versus 61 of 83 048 cases, <i>P </i>< 0.05). In bivariate analyses, MRSA SSI patients were significantly older, had higher BMI and more comorbidities compared to MSSA (<i>P </i>< 0.05 each). Surgery performed between 6:00 and 12:00 pm led to higher MRSA proportions among <i>S. aureus</i> SSI (17 of 104 cases versus 62 of 640 cases, <i>P </i>< 0.05).</p><p><strong>Conclusions: </strong>This study shows low overall and country-specific incidence rates of MRSA SSI in Europe. We could show significant differences between countries as well as between centres with established ABS and ID consultation programmes were observed. The number of those programmes seems too small against this background.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"6 2","pages":"dlae046"},"PeriodicalIF":3.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10993902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interprofessional education in antimicrobial stewardship, a collaborative effort.","authors":"Sarentha Chetty, Khine Swe Swe-Han, Yesholata Mahabeer, Ashendri Pillay, Sabiha Y Essack","doi":"10.1093/jacamr/dlae054","DOIUrl":"10.1093/jacamr/dlae054","url":null,"abstract":"<p><strong>Introduction: </strong>Antimicrobial stewardship (AMS) education and interprofessional collaboration are integral to the success of a stewardship programme. An interactive interprofessional AMS workshop, designed to encourage workplace interprofessional collaboration was piloted in a tertiary hospital.</p><p><strong>Objectives: </strong>To obtain feedback to determine the suitability and sustainability of the AMS workshop.</p><p><strong>Methods: </strong>Feedback was elicited through a predesigned questionnaire containing both open-ended and closed questions on the content and structure of the workshop.</p><p><strong>Results: </strong>The survey had a 70% (<i>n</i> = 16) overall response rate. All participants agreed that the goals of the workshop were met and that the knowledge and skills gained from the workshop would help them in their AMS roles. All participants indicated that the workshop content, and the level at which it was pitched, met their expectations and that it had improved their knowledge and skills. All agreed that they found it advantageous and enjoyed learning as an interprofessional group. Open feedback showed that the workshop was found to be useful and would potentially result in improved patient care, dissemination of knowledge, improved teamwork and organizational culture.</p><p><strong>Conclusions: </strong>The positive feedback and changes made following the workshop demonstrated that a targeted AMS educational workshop adds value to an antimicrobial stewardship programme.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"6 2","pages":"dlae054"},"PeriodicalIF":3.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10984567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rates of resistance and heteroresistance to newer β-lactam/β-lactamase inhibitors for carbapenem-resistant Enterobacterales.","authors":"Christina K Lin, Alex Page, Sarah Lohsen, Ali A Haider, Jesse Waggoner, Gillian Smith, Ahmed Babiker, Jesse T Jacob, Jessica Howard-Anderson, Sarah W Satola","doi":"10.1093/jacamr/dlae048","DOIUrl":"10.1093/jacamr/dlae048","url":null,"abstract":"<p><strong>Background: </strong>Heteroresistance (HR), the presence of antibiotic-resistant subpopulations within a primary isogenic population, may be a potentially overlooked contributor to newer β-lactam/β-lactamase inhibitor (BL/BLI) treatment failure in carbapenem-resistant Enterobacterales (CRE) infections.</p><p><strong>Objectives: </strong>To determine rates of susceptibility and HR to BL/BLIs ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam in clinical CRE isolates.</p><p><strong>Methods: </strong>The first CRE isolate per patient per year from two >500 bed academic hospitals from 1 January 2016 to 31 December 2021, were included. Reference broth microdilution (BMD) was used to determine antibiotic susceptibility, and population analysis profiling (PAP) to determine HR. Carbapenemase production (CP) was determined using the Carba NP assay.</p><p><strong>Results: </strong>Among 327 CRE isolates, 46% were <i>Enterobacter cloacae</i>, 38% <i>Klebsiella pneumoniae</i> and 16% <i>Escherichia coli</i>. By BMD, 87% to 98% of CRE were susceptible to the three antibiotics tested. From 2016 to 2021, there were incremental decreases in the rates of susceptibility to each of the three BL/BLIs. HR was detected in each species-antibiotic combination, with the highest rates of HR (26%) found in <i>K. pneumoniae</i> isolates with imipenem/relebactam. HR or resistance to at least one BL/BLI by PAP was found in 24% of CRE isolates and 65% of these had detectable CP.</p><p><strong>Conclusion: </strong>Twenty-four percent of CRE isolates tested were either resistant or heteroresistant (HR) to newer BL/BLIs, with an overall decrease of ∼10% susceptibility over 6 years. While newer BL/BLIs remain active against most CRE, these findings support the need for ongoing antibiotic stewardship and a better understanding of the clinical implications of HR in CRE.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"6 2","pages":"dlae048"},"PeriodicalIF":3.4,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10957161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of pyrazinamide resistance in <i>Mycobacterium tuberculosis</i> using structure-based machine-learning approaches.","authors":"Joshua J Carter, Timothy M Walker, A Sarah Walker, Michael G Whitfield, Glenn P Morlock, Charlotte I Lynch, Dylan Adlard, Timothy E A Peto, James E Posey, Derrick W Crook, Philip W Fowler","doi":"10.1093/jacamr/dlae037","DOIUrl":"10.1093/jacamr/dlae037","url":null,"abstract":"<p><strong>Background: </strong>Pyrazinamide is one of four first-line antibiotics used to treat tuberculosis; however, antibiotic susceptibility testing for pyrazinamide is challenging. Resistance to pyrazinamide is primarily driven by genetic variation in <i>pncA</i>, encoding an enzyme that converts pyrazinamide into its active form.</p><p><strong>Methods: </strong>We curated a dataset of 664 non-redundant, missense amino acid mutations in PncA with associated high-confidence phenotypes from published studies and then trained three different machine-learning models to predict pyrazinamide resistance. All models had access to a range of protein structural-, chemical- and sequence-based features.</p><p><strong>Results: </strong>The best model, a gradient-boosted decision tree, achieved a sensitivity of 80.2% and a specificity of 76.9% on the hold-out test dataset. The clinical performance of the models was then estimated by predicting the binary pyrazinamide resistance phenotype of 4027 samples harbouring 367 unique missense mutations in <i>pncA</i> derived from 24 231 clinical isolates.</p><p><strong>Conclusions: </strong>This work demonstrates how machine learning can enhance the sensitivity/specificity of pyrazinamide resistance prediction in genetics-based clinical microbiology workflows, highlights novel mutations for future biochemical investigation, and is a proof of concept for using this approach in other drugs.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"6 2","pages":"dlae037"},"PeriodicalIF":3.4,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"14-Year Epidemiologic study of <i>Pseudomonas aeruginosa</i> bloodstream infection incidence and resistance in the Veterans Health Administration system, 2009-2022.","authors":"Leila S Hojat, Brigid M Wilson, Michael J Satlin, Federico Perez, Maria F Mojica, Mendel E Singer, Robert A Bonomo, Lauren H Epstein","doi":"10.1093/jacamr/dlae031","DOIUrl":"10.1093/jacamr/dlae031","url":null,"abstract":"<p><strong>Background: </strong>Multidrug resistant <i>Pseudomonas aeruginosa</i> (PA) represents a serious threat to hospitalized patients. Characterizing the incidence of PA infection and degree of resistance can inform empiric treatment and preventative measures.</p><p><strong>Objectives: </strong>We sought to describe trends in incidence and resistance characteristics of PA bloodstream infections (BSI) observed within the Veterans Health Administration (VHA) system and identify factors contributing to higher observed mortality within this population.</p><p><strong>Methods: </strong>We characterized demographic and clinical features of unique patients among the VHA population presenting with their first episode of PA-BSI between 2009 and 2022 and summarized trends related to mortality and resistance phenotype based on year and geographical location. We additionally used logistic regression analysis to identify predictors of 30-day mortality among this cohort.</p><p><strong>Results: </strong>We identified 8039 PA-BSIs during the study period, 32.7% of which were hospital onset. Annual PA-BSI cases decreased by 35.8%, and resistance among all antimicrobial classes decreased during the study period, while the proportion of patients receiving early active treatment based on susceptibility testing results increased. Average 30-day mortality rate was 23.3%. Higher Charlson Comorbidity Index, higher mAPACHE score, VHA facility complexity 1b and hospital-onset cases were associated with higher mortality, and early active treatment was associated with lower mortality.</p><p><strong>Conclusions: </strong>PA-BSI resistance decreased across the VHA system during the study period. Further investigation of antimicrobial stewardship measures possibly contributing to the observed decreased resistance in this cohort and identification of measures to improve on the high mortality associated with PA-BSI in the VHA population is warranted.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"6 2","pages":"dlae031"},"PeriodicalIF":3.4,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10914452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}