Yang Guo, Jing Lu, Peipei Jin, Zhipeng Qiu, Fangyou Yu, Yan Zhu, Jiayuan Huang
{"title":"Genomic characterization of multidrug-resistant tuberculosis in Shanghai, China: antibiotic resistance, virulence and transmission.","authors":"Yang Guo, Jing Lu, Peipei Jin, Zhipeng Qiu, Fangyou Yu, Yan Zhu, Jiayuan Huang","doi":"10.1093/jacamr/dlaf064","DOIUrl":"10.1093/jacamr/dlaf064","url":null,"abstract":"<p><strong>Objectives: </strong>Whole-genome sequencing (WGS) was employed to investigate antibiotic resistance, virulence and transmission profiles of multidrug-resistant tuberculosis (MDR-TB) isolates from Shanghai, China.</p><p><strong>Methods: </strong>A total of 306 MDR-TB clinical isolates were collected from Shanghai Pulmonary Hospital and underwent phenotypic drug susceptibility testing (DST) for common anti-TB drugs and WGS. Combined 778 published bacterial sequences, we performed phylogenetic analysis, resistance and virulence gene identification to understand the genetic relationships and resistance mechanisms among those strains.</p><p><strong>Results: </strong>WGS determination, supported by DST, revealed high resistance rates for isoniazid (83.66%) and rifampicin (90.20%) among the MDR-TB isolates. Key resistance-associated mutations included <i>katG</i> Ser315Thr for isoniazid, <i>rpoB</i> mutations for rifampicin, and <i>embB</i> Met306Val for ethambutol. WGS demonstrated >90% concordance with culture-based DST for most drugs, except ethambutol that showed a 76.80% concordance. Analyses of virulence factors and phylogenetics revealed the genetically homogeneous, endemic MDR-TB population in Shanghai, with no evidence of recent transmission.</p><p><strong>Conclusions: </strong>This study highlights the genetic homogeneity and endemic nature of MDR-TB in Shanghai, providing insights into key resistance mechanisms of TB.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf064"},"PeriodicalIF":3.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063837","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":"Tracking Antimicrobial Resistant Organisms Timely: a workflow validation study for successive core-genome SNP-based nosocomial transmission analysis.","authors":"Kotaro Aoki, Kohji Komori, Tetsuo Yamaguchi, Sohei Harada, Mayumi Tsukada, Hinako Murakami, Kazuhiro Tateda","doi":"10.1093/jacamr/dlaf069","DOIUrl":"10.1093/jacamr/dlaf069","url":null,"abstract":"<p><strong>Background and objectives: </strong>Effective infection prevention and control (IPC) interventions in hospitals require timely information to determine the potential transmission of antimicrobial-resistant (AMR) organisms. We proposed and developed a successive core-genome SNP (cgSNP)-based phylogenetic analysis workflow, 'Tracking Antimicrobial Resistant Organisms Timely' (TAROT), using the Oxford Nanopore Technologies (ONT) sequencer for MRSA, and compared the results with those obtained using the Illumina sequencer.</p><p><strong>Methods: </strong>We have developed a TAROT workflow for successive phylogenetic analysis using ONT data. We sequenced 34 MRSA strains isolated from Toho University Omori Medical Center using MinION (ONT) and MiSeq (Illumina). Each strain's ONT data were inputted into TAROT (TAROT-ONT), and successive cgSNP-based phylogenetic analyses were conducted. Illumina data were processed with a batched cgSNP-based phylogenetic analysis. Assembly-based analysis identified AMR genes, AMR mutations and virulence genes.</p><p><strong>Results: </strong>MinION generated an average sequence depth of 262× for the ST8 reference genome within 3 h. TAROT-ONT successively generated 11 phylogenetic trees for 14 ST8 strains, 7 trees for 10 ST1 strains and 2 trees for 5 ST5 strains. Highly suspected transmission pairs (pairwise cgSNP< 5) were detected in trees #6 through #11 for ST8, trees #3, #5 and #7 for ST1, and tree #2 for ST5. Differences in pairwise cgSNP value between TAROT-ONT and Illumina ranged from zero to two within pairs with fewer than 20 cgSNPs using Illumina. TAROT-ONT bioinformatic analysis for each strain required 5-42 min. The identification of AMR genes, mutations and virulence genes showed high concordance between ONT and Illumina.</p><p><strong>Conclusions: </strong>TAROT-ONT can facilitate effective IPC intervention for MRSA nosocomial transmissions by providing timely feedback through successive phylogenetic analyses based on cgSNPs.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf069"},"PeriodicalIF":3.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965894","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}
Stella Babich, Pier Giorgio Cojutti, Milo Gatti, Federico Pea, Stefano Di Bella, Jacopo Monticelli
{"title":"Feasibility of 24 h continuous-infusion cefiderocol administered by elastomeric pump in attaining an aggressive PK/PD target in the treatment of NDM-producing <i>Klebsiella pneumoniae</i> otomastoiditis.","authors":"Stella Babich, Pier Giorgio Cojutti, Milo Gatti, Federico Pea, Stefano Di Bella, Jacopo Monticelli","doi":"10.1093/jacamr/dlaf066","DOIUrl":"10.1093/jacamr/dlaf066","url":null,"abstract":"<p><strong>Objectives: </strong>Cefiderocol has emerged as a key treatment for managing MDR infections, and its time-dependent pharmacodynamics are optimized by prolonged infusion to maintain time above the MIC (<i>T</i> <sub> > MIC</sub>). Whereas recent stability studies have shown cefiderocol remains stable up to 72 h in elastomeric pumps, its use in 24 h continuous infusions (CIs) for outpatient parenteral antibiotic therapy (OPAT) is undocumented. This case highlights its suitability for 24 h CI via elastomeric pumps in an OPAT setting, supported by therapeutic drug monitoring (TDM) to ensure optimal treatment efficacy.</p><p><strong>Patient/case description: </strong>A 31-year-old male developed right-sided otomastoiditis caused by <i>Klebsiella pneumoniae</i> producing New Delhi MBL (NDM). Given the resistance profile and the need for prolonged therapy, cefiderocol was initiated at a daily dose of 6 g, administered by 24 h CI using an elastomeric pump. TDM was performed on Days 17 and 45 to assess plasma concentrations.</p><p><strong>Results: </strong>TDM confirmed steady-state concentrations (<i>C</i> <sub>ss</sub> 25.2-28.1 mg/L), achieving optimal pharmacokinetic/pharmacodynamic (PK/PD) target attainment such as 100% <i>T</i> <sub> > 4-6 MIC</sub> (free [<i>f</i>]<i>C</i> <sub>ss</sub>/MIC 10.58-11.80). Significant clinical improvement avoided the need for planned surgery, with no adverse events reported from the venous catheter, antibiotic therapy or elastomeric pump.</p><p><strong>Conclusions: </strong>This approach underscores the feasibility and efficacy of cefiderocol administered by 24 h CI by means of an elastomeric pump and supported by real-time TDM in achieving an aggressive PK/PD target for the treatment of otomastoiditis due to NDM-producing <i>K. pneumoniae</i>.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf066"},"PeriodicalIF":3.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12050970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035289","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":"Significant reduction in antibiotic prescription rates in Japan following implementation of the national action plan on antimicrobial resistance (2016-20): a 9-year interrupted time-series analysis.","authors":"Hideki Hashimoto, Naoki Kanda, Hiromasa Yoshimoto, Kazuo Goda, Naohiro Mitsutake, Shuji Hatakeyama","doi":"10.1093/jacamr/dlaf062","DOIUrl":"10.1093/jacamr/dlaf062","url":null,"abstract":"<p><strong>Background: </strong>Research on the effectiveness of Japan's national action plan on antimicrobial resistance, including among individuals with HIV, remains scarce.</p><p><strong>Objectives: </strong>To evaluate the impact of policies on antibiotic prescription practices.</p><p><strong>Methods: </strong>Outpatient oral antibiotic prescription data from 2012 to 2020 were extracted from a national claims database comprising >98% of the Japanese population. Prescription rates were stratified according to antibiotic class, diagnosis and HIV status. An interrupted time-series analysis was performed to assess the impact of the national action plan.</p><p><strong>Results: </strong>An average of 129,989,400 prescriptions were issued annually (1024 per 1000 population-years). Between 2012 and 2020, the oral antibiotic prescription rate decreased by 54%. The prescription rate showed a significant downward trend post-intervention (additional annual reduction in incidence rate ratio, 0.889; 95% confidence interval, 0.889-0.990). However, broad-spectrum antibiotics (third-generation cephalosporins, macrolides and fluoroquinolones) remained prevalent, comprising 84.7% and 71.4% of prescriptions in 2012 and 2020, respectively. Antibiotic prescriptions during outpatient visits for pharyngitis, sinusitis, bronchitis and viral upper respiratory infections decreased significantly (rate ratios = 0.66, 0.76, 0.51 and 0.49, respectively). The antibiotic prescription rate was ∼2.5-fold higher in individuals with HIV than in those without.</p><p><strong>Conclusions: </strong>Antibiotic prescription rates significantly decreased following the implementation of the national action plan. However, a sharp decline in 2020, likely due to the coronavirus disease pandemic, requires continued rebound monitoring. Reducing broad-spectrum oral antibiotic overuse remains a critical focus.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf062"},"PeriodicalIF":3.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015829","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}
Iacopo Franconi, Noemi Poma, Cosmeri Rizzato, Lorenzo Maltinti, Marco Falcone, Arianna Tavanti, Antonella Lupetti
{"title":"The S862C amino acid change in CpMrr1 confers fluconazole resistance in <i>Candida parapsilosis</i>.","authors":"Iacopo Franconi, Noemi Poma, Cosmeri Rizzato, Lorenzo Maltinti, Marco Falcone, Arianna Tavanti, Antonella Lupetti","doi":"10.1093/jacamr/dlaf051","DOIUrl":"10.1093/jacamr/dlaf051","url":null,"abstract":"<p><strong>Background: </strong><i>Candida parapsilosis</i> is an opportunistic pathogen with increasing rates of resistance to fluconazole and voriconazole. Recently, in an outbreak at the Azienda Ospedaliero-Universitaria Pisana, a new amino acid substitution, S862C in the CpMrr1 protein, was found only in azole-resistant strains. The contribution of this mutation to the acquisition of an azole-resistant phenotype was investigated in this study.</p><p><strong>Methods: </strong>Antifungal resistance in <i>C. parapsilosis</i> clinical strains isolated from the outbreak (<i>n</i> = 16) was tested by the broth microdilution method and Etest strip. WGS and Sanger sequencing analyses were used for the detection of SNPs. A CRISPR-Cas9-based genome editing strategy was used to induce the C2585G substitution in the <i>CpMRR1</i> gene of susceptible <i>C. parapsilosis</i> isolates to investigate its role in the acquisition of azole resistance.</p><p><strong>Results: </strong>The A395T and the newly found C2585G substitution in the <i>CpMRR1</i> gene were present in all resistant isolates, but not in the susceptible ones. Such mutations were later induced in the <i>C. parapsilosis</i> reference strain ATCC 22019 and in two azole-susceptible clinical isolates in homozygosis, and in heterozygosis only for ATCC 22019 and one azole-susceptible clinical isolate. Both heterozygous and homozygous mutants carrying the C2585G mutation were fluconazole resistant, with some clones also presenting intermediate susceptibility or resistance to voriconazole.</p><p><strong>Conclusions: </strong>To the best of our knowledge, this is the first study to report the effect on azole resistance of a novel C2585G nucleotide substitution in the <i>CpMRR1</i> gene found in clinical isolates recovered during an outbreak of azole-resistant <i>C. parapsilosis</i> in a healthcare setting.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf051"},"PeriodicalIF":3.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002921","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}
Nicole L Kavanagh, Peter M Kinnevey, Grainne I Brennan, Brian O'Connell, Richard V Goering, David C Coleman
{"title":"Co-carriage of diverse vancomycin-resistant <i>Enterococcus faecium</i> ST80-lineages by 70% of patients in an Irish hospital.","authors":"Nicole L Kavanagh, Peter M Kinnevey, Grainne I Brennan, Brian O'Connell, Richard V Goering, David C Coleman","doi":"10.1093/jacamr/dlaf065","DOIUrl":"10.1093/jacamr/dlaf065","url":null,"abstract":"<p><strong>Background: </strong>Vancomycin-resistant <i>Enterococcus faecium</i> (VREfm) are significant nosocomial pathogens. Irish VREfm comprise diverse <i>vanA</i>-encoding ST80-complex type (CT) lineages. Recent studies indicate that within-patient VREfm diversity could confound surveillance. This study investigated the intra-host VREfm genetic diversity among colonized Irish hospital patients.</p><p><strong>Methods: </strong>Rectal VREfm (<i>n</i> = 150) from 10 patients (15 isolates each) were investigated by WGS, core-genome MLST and split <i>k-mer</i> (SKA)-SNP analysis. Plasmids and <i>vanA</i>-transposons from 39 VREfm representative of CTs identified were resolved by hybrid assembly of short-read (Illumina) and long-read (Oxford Nanopore Technologies) sequences. Plasmid relatedness was assessed based on Mash distances. Thirty vancomycin-susceptible <i>E. faecium</i> (VSEfm) from four VREfm-positive patients were also investigated.</p><p><strong>Results: </strong>All isolates were clade A1 and most were ST80 (VREfm, 147/150; VSEfm, 25/30). Seventy-percent of patients (7/10) harboured either two (<i>n</i> = 4), three (<i>n</i> = 2) or four (<i>n</i> = 1) VREfm CTs. Individual patient isolate pairs from different CTs differed significantly (median SKA-SNPs 2933), but differences were minimal between isolate pairs of the same CT (median SKA-SNPs 0). In total, 193 plasmids were identified in 39 VREfm investigated. Near-identical plasmids (≥99.5% average nucleotide identity) were identified in divergent CTs from multiple patients. Most VREfm (28/39, 72%) harboured <i>vanA</i> on closely related transferable, linear plasmids. Divergent CTs within individual patients harboured either indistinguishable <i>vanA</i>-transposons or <i>vanA</i>-transposons with distinct organizational iterations. Four VSEfm from different CTs investigated harboured similar plasmids to VREfm.</p><p><strong>Conclusion: </strong>VREfm within-host diversity is highly prevalent in Irish hospital patients, which complicates surveillance. Linear plasmids play an important role in the emergence of Irish VREfm.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf065"},"PeriodicalIF":3.7,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997060","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":"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}
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
{"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> <sub>NDM-1</sub> 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}
Monica Augustyniak, Juan Carlos García-Betancur, Sophie Péloquin, Germán Esparza, Christian José Pallares, Diego Rosselli, David De Luna, Patrice Lazure, Maria Virginia Villegas
{"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}