JAC-Antimicrobial Resistance最新文献

{"title":"HIV-1 cross-resistance to second-generation non-nucleoside reverse transcriptase inhibitors among individuals failing antiretroviral therapy in Cameroon: implications for the use of long-acting treatment regimens in low- and middle-income countries.","authors":"Davy-Hyacinthe Gouissi Anguechia, Yagai Bouba, Ezechiel Ngoufack Jagni Semengue, Desire Takou, Collins Ambe Chenwi, Vincent Kamaël Mekel, Grace Angong Beloumou, Alex Durand Nka, Aude Christelle Ka'e, Sandrine Claire Ndjeyep Djupsa, Vittorio Colizzi, Nicaise Ndembi, Alexis Ndjolo, Dora Mbanya, Carlo-Federico Perno, Joseph Fokam","doi":"10.1093/jacamr/dlaf059","DOIUrl":"https://doi.org/10.1093/jacamr/dlaf059","url":null,"abstract":"<p><strong>Background: </strong>Several long-acting antiretroviral treatment regimens contain second-generation non-nucleoside reverse transcriptase inhibitors (2ndGenNNRTI). As first-generation NNRTIs (1stGenNNRTI) exhibit some cross-resistance with 2ndGenNNRTI, we sought to evaluate the rate of acquired cross-resistance to 2ndGenNNRTI and its determinants at treatment failure in a typical low- and middle-income country (LMIC) such as Cameroon.</p><p><strong>Patients and methods: </strong>A facility-based cross-sectional study was conducted among patients failing first-/second-line regimens between 2019 and 2023 in Cameroon. HIV-1 Sanger sequencing was performed on plasma and resistance-associated mutations (RAMs) to etravirine, rilpivirine and doravirine were interpreted using HIVdb program v.9.5.0 (HIVdb penalty scores were,  ≥60, high resistance; 15-59, intermediate resistance and  <15, susceptible) and the IAS-USA 2022 list.</p><p><strong>Results: </strong>Overall, 653 individuals previously exposed to 1stGenNNRTI were enrolled [median (IQR) age 39 (26-46) years and viraemia 59 370 (10 442-244 916) copies/mL]. Importantly, 361 participants were on 1stGenNNRTI-based first-line and 292 on protease inhibitor-based second-line regimen. NNRTIs RAMs were found in up to 90.64% of individuals, with 36.45% having more than three RAMs. Concerning 2ndGenNNRTIs, 77.18% of individuals harboured RAMs conferring high or intermediate-level resistance, with the predicted efficacy of etravirine, doravirine and rilpivirine being 47.17%, 33.23% and 32.31%, respectively. Major 2ndGenNNRTIs RAMs were driven by Y181C (23.74%), K101E (8.57%), Y188L (8.42%) and H221Y (8.42%), while minor RAMs were A98G (18.83%), G190A (18.68%) and P225H (14.70%). A higher prevalence of RAMs was observed in those failing first-line versus second line (81.71% versus 71.57%, respectively, <i>P</i> < 0.001), driven predominantly by the difference in doravirine-RAMs [first line (72.85%) versus second line (59.58%), <i>P</i> < 0.001].</p><p><strong>Conclusions: </strong>Among patients failing treatment in Cameroon, there is a high-level of cross-resistance to 2ndGenNNRTI due to wide exposure to 1stGenNNRTI. Thus, in LMICs sharing similar programmatic features, the use of NNRTI-sparing regimens should be prioritized as a public health approach, while second-generation-NNRTI long-acting regimens should be guided by genotyping or for clients without previous exposure to NNRTIs.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 2","pages":"dlaf059"},"PeriodicalIF":3.7,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024209","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":"Mitigating inequitable access to appropriate antibiotics in low- and middle-income countries.","authors":"Idemudia Imonikhe Otaigbe","doi":"10.1093/jacamr/dlaf061","DOIUrl":"https://doi.org/10.1093/jacamr/dlaf061","url":null,"abstract":"<p><p>Access to effective medicines (e.g. antibiotics) is a fundamental human right. However, in contrast to high-income countries (HICs), many low- and middle-income countries (LMICs) lack appropriate and effective antibiotics. This is a paradox, and an inequitable scenario, as LMICs can have significantly higher burdens of infectious diseases than HICs and especially require appropriate antibiotics. Inequitable access to appropriate antibiotics results in patients being treated with substandard antibiotics, treatment failure, the emergence of antimicrobial resistance (AMR) and, inevitably, morbidity and mortality. Factors that hinder access to appropriate antibiotics in LMICs include: poor political will, weak health systems, complex bureaucratic protocols, poor implementation of National Action Plans on AMR, inadequate expertise in regulatory science, unfavourable macroeconomic policies and a poor investment climate. Clearly, multisectoral, collaborative approaches are required to effectively mitigate inequitable access to appropriate antibiotics in LMICs. Also, efforts (such as the African Medicines Regulatory Harmonization Initiative and the African Medicines Agency) to streamline bureaucratic processes and improve the registration and entry of appropriate antibiotics into LMICs are required. This review discusses factors responsible for inequitable access to appropriate antibiotics in LMICs, and makes recommendations to mitigate the problem. With rising rates of AMR, a dwindling antibiotic pipeline, and the dangers of a post-antibiotic era, it is clear that the time to act is now, as inequitable access to appropriate antibiotics in LMICs reduces the quality of healthcare, and threatens the achievement of Universal Health Coverage and, ultimately, the Sustainable Development Goals.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 2","pages":"dlaf061"},"PeriodicalIF":3.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12019631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020602","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":"Analysis of intrahospital and global dissemination and resistome dynamics of NDM-1-producing ST773 <i>Pseudomonas aeruginosa</i> high-risk clone.","authors":"Cristina Pitart, Gabriel Taltavull, Carla López-Causapé, Andrea Pulgarín, Sergi De Gea, Mireia Aguilar, Xavier Mulet, Gabriel Cabot, Jordi Vila, Ignasi Roca, Mateu Espasa, Climent Casals-Pascual, Antonio Oliver","doi":"10.1093/jacamr/dlaf063","DOIUrl":"https://doi.org/10.1093/jacamr/dlaf063","url":null,"abstract":"<p><strong>Objectives: </strong>To analyse the intrahospital and global dissemination and resistome dynamics of the concerning NDM-1 MBL-producing ST773 <i>P. aeruginosa</i> high-risk clone.</p><p><strong>Methods: </strong>A total of 17 NDM-1-producing <i>P. aeruginosa</i> isolates recovered in 2022-24 from 10 patients at Hospital Clinic of Barcelona (HCB), Spain, were studied through susceptibility testing and WGS. Expression of resistance genes was analysed through quantitative (real-time) RT-PCR. Forty ST773 genomes from isolates recovered worldwide were also incorporated in the phylogenetic and resistome analysis.</p><p><strong>Results: </strong>All HCB NDM-1-producing isolates were assigned to ST773 except one (ST357 additionally producing VEB-9 and linked epidemiologically to India). The index ST773 case was a 41-year-old woman admitted to the oncology ward in February 2022 after breast cancer surgery in Ukraine. These isolates were closely related and the <i>bla</i> _NDM-1 gene was located in the same 117 kb integrative conjugative element. All ST773-NDM-1 producers from HCB and the 40 worldwide isolates shared the same acquired resistance determinants [<i>aadA11-</i>like, <i>rmtB4</i>, <i>qnrVC1</i> and <i>tet</i>(G)], as well as some of the antibiotic resistance mutations (<i>mexZ</i>, <i>mexT</i>, <i>gyrA</i> and <i>parC</i>). Other specific mutations such as an <i>oprD</i> deletion were shared only with isolates from Ukrainian patients transferred to Madrid or the Netherlands. Lastly, HCB isolates evolved further resistome mutations during intrahospital dissemination, including regulators of AmpC (<i>mpl</i>) and MexAB-OprM (<i>nalD</i>), linked to the acquisition of aztreonam/avibactam resistance, and thus remaining only susceptible to cefiderocol and colistin.</p><p><strong>Conclusions: </strong>This work evidences the transborder spread and intrahospital dissemination and evolution of the emerging ST773-NDM-1 <i>P. aeruginosa</i> high-risk clone.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 2","pages":"dlaf063"},"PeriodicalIF":3.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990117","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":"Promoting real-world evidence use for antimicrobial stewardship in Latin America: evaluation of impact of a two-part educational webinar series.","authors":"Monica Augustyniak, Juan Carlos García-Betancur, Sophie Péloquin, Germán Esparza, Christian José Pallares, Diego Rosselli, David De Luna, Patrice Lazure, Maria Virginia Villegas","doi":"10.1093/jacamr/dlaf056","DOIUrl":"https://doi.org/10.1093/jacamr/dlaf056","url":null,"abstract":"<p><strong>Background: </strong>Educational programs on the use of real-world evidence (RWE) in antimicrobial stewardship (AMS) are scarce in Latin America (LATAM).</p><p><strong>Objectives: </strong>To develop and evaluate an online educational program supporting LATAM healthcare professionals (HCP)'s ability to use and generate RWE for effective antimicrobial agent use, aligned with AMS principles.</p><p><strong>Methods: </strong>Two 90-min webinars were developed by subject matter experts. Changes in knowledge, skills, confidence and attitudes were measured via paired PRE-and POST-intervention survey questions. Satisfaction, intent to change and remaining barriers were surveyed POST-intervention. McNemar and Wilcoxon Signed Rank statistical tests assessed differences in paired dichotomous and ordinal data, respectively. Unpaired data underwent descriptive analysis. Open-ended responses were subject to thematic content analysis (inductive reasoning approach).</p><p><strong>Results: </strong>The analysis sample included 741 PRE-intervention survey completers (epidemiologists, infection control specialists, chemists, pharmacists, biologists, microbiologists, bacteriologists and other physicians), with 47 completing the full POST survey (33 following webinar 1, and 14 following webinar 2). A significant increase in the percent of completers who were confident of 'what constitutes RWE' was found PRE (31%) to POST (73%) intervention (<i>P</i> < 0.001). Median self-reported skill levels changed from '2-basic' to '3-intermediate' for providing examples of RWE and applying RWE in the context of AMS (<i>P</i> < 0.05). Barriers included low perceived value of RWE by administrators and limited access to appropriate data.</p><p><strong>Conclusions: </strong>This education improved HCPs' confidence in knowing what constitutes RWE. Findings provide direction for future interventions aimed at enhancing access to and appropriate use of RWE to inform AMS in LATAM.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 2","pages":"dlaf056"},"PeriodicalIF":3.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012767","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":"Impact of milbemycin oxime on fluconazole resistance in <i>Candida auris</i>.","authors":"Lola Aubry, Danielle Brandalise, Marine Louvet, Alix T Coste, Dominique Sanglard, Frederic Lamoth, Jizhou Li","doi":"10.1093/jacamr/dlaf060","DOIUrl":"https://doi.org/10.1093/jacamr/dlaf060","url":null,"abstract":"<p><strong>Background: </strong><i>Candida auris</i> is a pathogenic yeast that can develop resistance to multiple antifungals, particularly to azoles (e.g. fluconazole). Milbemycin oxime potentiates the effect of fluconazole against <i>Candida</i> spp. by inhibiting ABC transporters, such as Cdr1, which is involved in azole drug efflux.</p><p><strong>Objectives: </strong>This study aimed to assess the interaction of milbemycin oxime and fluconazole against clinical (<i>n</i> = 4) and laboratory-generated (<i>n</i> = 4) <i>C. auris</i> isolates with different mechanisms of azole resistance.</p><p><strong>Methods: </strong>Interactions of milbemycin oxime and fluconazole were assessed by chequerboard assays and defined as synergistic, indifferent or antagonistic according to the FIC index (FICI) values. The fluorescent substrate rhodamine 6 g (R6G) was used to measure ABC transporter activity in the absence or presence of milbemycin oxime.</p><p><strong>Results: </strong>A synergistic interaction between milbemycin oxime and fluconazole was observed against most isolates, including those harbouring Cdr1-independent mechanisms of azole resistance (e.g. <i>ERG11</i> mutations). The highest synergism was observed in a laboratory-generated strain overexpressing <i>CDR1</i>, while the interaction was indifferent in a strain lacking <i>CDR1</i>. R6G experiments confirmed the inhibitory effect of milbemycin oxime on ABC transporters.</p><p><strong>Conclusions: </strong>Milbemycin oxime could represent an interesting adjunctive therapy against azole-resistant <i>C. auris</i>, particularly those with <i>CDR1</i> overexpression.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 2","pages":"dlaf060"},"PeriodicalIF":3.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987895","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":"Sulbactam for carbapenem-resistant <i>Acinetobacter baumannii</i> infections: a literature review.","authors":"Nikolaos Spernovasilis, Angela Ishak, Constantinos Tsioutis, Danny Alon-Ellenbogen, Aris P Agouridis, Nikolaos Mazonakis","doi":"10.1093/jacamr/dlaf055","DOIUrl":"https://doi.org/10.1093/jacamr/dlaf055","url":null,"abstract":"<p><p>Carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) is characterized as a critical priority pathogen with restricted therapeutic options. To date, the most effective antimicrobial treatment against this difficult-to-treat bacterial strain has not been established. Sulbactam is a β-lactamase inhibitor with intrinsic activity against this pathogen, however, as a β-lactam, it can be hydrolysed by β-lactamases produced by <i>A. baumannii</i>. High-dose, extended-infusion treatment with sulbactam can overcome this hydrolysis by β-lactamases and is considered an effective therapeutic strategy against CRAB. The aim of this review is to analyse primary and secondary research studies that compare sulbactam-based with other regimens, such as polymyxin-containing regimens, tigecycline-containing regimens and other antimicrobial combinations against CRAB infections, especially ventilator-associated pneumonia (VAP), hospital-acquired pneumonia (HAP) and bacteraemia. Our findings suggest that results are conflicting, mostly because of high heterogeneity among studies. However, in most studies, sulbactam-based regimens have demonstrated comparable, and in several studies more favourable results in contrast to other antimicrobial treatments with respect to clinical cure and mortality in CRAB-associated pneumonia, yet without reaching statistical significance in most cases. The auspicious novel β-lactam/β-lactamase inhibitor combination sulbactam/durlobactam is also discussed, although real-world clinical data regarding its efficacy in CRAB infections are still scarce. More randomized controlled trials comparing sulbactam-based with other regimens are warranted to determine the most effective antimicrobial combination against CRAB infections. Nevertheless, current data suggest that sulbactam could play a major role in this combination treatment.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 2","pages":"dlaf055"},"PeriodicalIF":3.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063835","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":"SAAP-148 and halicin exhibit synergistic antimicrobial activity against antimicrobial-resistant bacteria in skin but not airway epithelial culture models.","authors":"Patrick R Lennard, Pieter S Hiemstra, Julia R Dorin, Peter H Nibbering","doi":"10.1093/jacamr/dlaf050","DOIUrl":"https://doi.org/10.1093/jacamr/dlaf050","url":null,"abstract":"<p><strong>Background: </strong>The escalating global threat of antimicrobial resistance (AMR) necessitates the development of novel antimicrobial agents, innovative strategies, and representative infection models to combat AMR bacterial infections. Host defence peptides (HDPs) and their derivatives have been proposed as complements to conventional antibiotics due to their antibacterial activity and modulation of the immune response.</p><p><strong>Objectives: </strong>This study investigated the novel use of the HDP-derived synthetic antibacterial and anti-biofilm peptide (SAAP)-148 as a pretreatment in epithelial tissue models to prevent colonization by AMR bacteria. The combined activities of SAAP-148 pretreatment with post-infection halicin to treat infections were also explored.</p><p><strong>Methods: </strong>Employing cultured human skin equivalents (HSEs) and primary bronchial epithelial cells (PBECs) as models of tissue infection, we examined the prophylactic and therapeutic effects of SAAP-148, both singularly and in combination with the repurposed antibiotic halicin, against AMR bacteria. We additionally interrogated the response of HSE and PBEC cultures to SAAP-148 treatment via confocal microscopy and quantitative PCR of native HDPs and inflammatory cytokine genes.</p><p><strong>Results: </strong>Our findings demonstrated that pretreatment with SAAP-148 significantly reduces colonization of HSEs and PBECs by AMR <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>. Confocal microscopy revealed differential uptake and localization of SAAP-148 in these tissues, correlating with its distinct activity in these tissues. SAAP-148 exposure temporarily increased expression of the HDPs cathelicidin (<i>CAMP</i>) and β-defensin 1 (<i>DEFB1</i>), and the cytokine IL-8 (<i>CXCL8</i>), which did not correlate with the transient antibacterial activity observed. Sequential treatment with SAAP-148 prior to infection with AMR <i>S. aureus</i> and post-infection halicin treatment demonstrated synergistic activity in HSEs, whereas this combined activity was indifferent in PBEC cultures.</p><p><strong>Conclusions: </strong>These results support SAAP-148 as a candidate for pre-infection prophylaxis and synergistic antibiotic therapy with halicin in skin, broadening the potential of both agents to address AMR bacterial infection.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 2","pages":"dlaf050"},"PeriodicalIF":3.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008944","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":"Simulation-based evaluation of the impact of dose fractionation study design on antibiotic PKPD analyses.","authors":"Raphaël Saporta, Muskan Madan, Lena E Friberg","doi":"10.1093/jacamr/dlaf057","DOIUrl":"https://doi.org/10.1093/jacamr/dlaf057","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the impact of antibiotic dose fractionation study design on pharmacokinetic/pharmacodynamic (PK/PD) indices and PKPD model estimation.</p><p><strong>Methods: </strong>PKPD models for meropenem and polymyxin B (PMB) were applied to (i) simulate various dose fractionation studies in mice to derive PK/PD indices and efficacy targets and (ii) perform stochastic simulations and estimations evaluating which efficacy assessment times, in addition to 24 h, would improve the estimation of drug effect parameters.</p><p><strong>Results: </strong>The <i>R</i> ² values of PK/PD indices were primarily influenced by reductions of the dosing intervals for meropenem and by decreases of the lowest total daily dose for PMB. For certain study designs (e.g. frequent administration of higher meropenem doses), <i>R</i> ² values for <i>f</i>T > MIC and <i>f</i>AUC/MIC were similar. Efficacy target magnitudes were also sensitive to the selected doses. Additional efficacy assessment times improved parameter accuracy (e.g. 40% reduction in relative root mean squared error of PMB effect slope). The model parameter accuracy was more affected by the selection of time points for meropenem, which included resistance, than for PMB. Efficacy measurements in the first hours after treatment start (e.g. 2 and 6 h), in addition to 24 h, were essential for resistance characterization.</p><p><strong>Conclusions: </strong>The choice of doses and fractionations impacted PK/PD index selection and efficacy target magnitude. Depending on the antibiotic, the dose or fractionation selection appeared to be the most critical. Early treatment efficacy measurements were beneficial to PKPD model-based analyses, particularly to describe resistance processes.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 2","pages":"dlaf057"},"PeriodicalIF":3.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969904","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":"Fosfomycin-resistant <i>Escherichia coli</i>: a FosA10 case in Italy.","authors":"Vittoria Mattioni Marchetti, Ilaria Petrizzi, Irene Venturelli, Tiziana Cassetti, Marianna Meschiari, Roberta Migliavacca, Ibrahim Bitar","doi":"10.1093/jacamr/dlaf052","DOIUrl":"https://doi.org/10.1093/jacamr/dlaf052","url":null,"abstract":"<p><strong>Background: </strong>FosA10-producing Enterobacterales have an extremely low incidence in Europe.</p><p><strong>Patients and methods: </strong>In March 2024, an 83-year-old woman, hospitalized in the Modena Province, developed an infection with fosfomycin-resistant <i>Escherichia coli</i>. The patient was treated with piperacillin/tazobactam and, after 10 days, the clinical picture was resolved. Fosfomycin MIC was evaluated with the reference agar dilution method and the production of FosA enzymes by phenotypic testing. Genomic characterization was assessed using long-read sequencing technology on the Sequel I platform.</p><p><strong>Results: </strong>An <i>E. coli</i> isolate (FO_2) was collected from both blood and urine samples and showed high-level resistance to fosfomycin (MIC > 128 mg/L). The resistance to fosfomycin was ascribed to the production of FosA-like enzymes by phenotypic testing. The genomic analysis pointed to a FosA10-producing <i>E. coli</i> ST69. The <i>fosA10</i> gene was carried by a highly conjugative IncB/O/K/Z plasmid that showed relevant similarities with other globally circulating plasmids.</p><p><strong>Conclusions: </strong>The acquisition of rare <i>fosA</i>-like genes in clinically relevant clones is concerning and the dissemination of FosA-producing <i>E. coli</i> should be continuously monitored.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 2","pages":"dlaf052"},"PeriodicalIF":3.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11979095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004537","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":"<i>Pseudomonas aeruginosa</i> chronic infections in patients with bronchiectasis: a silent reservoir of carbapenemase-producing epidemic high-risk clones.","authors":"Alba Muñoz-Santa, Carla López-Causapé, Alba Bellés, Xavier Gómez-Arbonés, Sara Cortés-Lara, Mercè García-González, Ricardo Pifarré-Teixidó, Antonio Oliver","doi":"10.1093/jacamr/dlaf053","DOIUrl":"10.1093/jacamr/dlaf053","url":null,"abstract":"<p><strong>Objectives: </strong><i>Pseudomonas aeruginosa</i> is one of the major drivers of morbidity and mortality in patients with chronic underlying diseases. Whereas cystic fibrosis (CF) <i>P. aeruginosa</i> strains have been well studied, non-CF bronchiectasis isolates have received less scientific attention.</p><p><strong>Methods: </strong>We determined the antibiotic susceptibility profiles of a collection of 100 <i>P. aeruginosa</i> isolates recovered from a total of 100 non-CF bronchiectasis patients attending a Catalonian hospital. All carbapenemase-producing isolates were characterized by WGS.</p><p><strong>Results: </strong>Twelve isolates were classified as MDR (12%) and six were found to be carbapenemase (VIM-2) producers (6%). Of note, two of the VIM-2-producing isolates were carbapenem susceptible due to the presence of inactivating mutations in MexAB-OprM efflux pump components. These isolates exhibited properties of chronic <i>P. aeruginosa</i> isolates, such as mutator or mucoid phenotypes that are associated with persistent infections despite intensive antibiotic therapies. The phylogenetic analysis evidenced that all VIM-2 isolates belonged to the high-risk clone ST235. Core-genome MLST analysis revealed 7-260 allelic differences, arguing against recent transmission but a common source of infection or an ancient interpatient transmission event could not be ruled out.</p><p><strong>Conclusions: </strong>Altogether, these findings suggest that <i>P. aeruginosa</i> chronic respiratory infections can be an important and silent reservoir of transferable resistance determinants and <i>P. aeruginosa</i> high-risk clones, thus contributing to their increased resistance and worldwide dissemination.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 2","pages":"dlaf053"},"PeriodicalIF":3.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811119","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}