Journal of Antimicrobial Chemotherapy最新文献

{"title":"Pharmacokinetics and safety of rifapentine in children: dosing for latent tuberculosis infection.","authors":"Weijian Liu, Nuo Xu, Wei Li, Wen Yao Mak, Tian He, Hongjuan Qin, Shuihua Lu, Hongzhou Lu, Xiaoqiang Xiang, Xiao Zhu, Peize Zhang","doi":"10.1093/jac/dkaf029","DOIUrl":"10.1093/jac/dkaf029","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the safety of 4-week daily rifapentine-isoniazid regimen in latent tuberculosis for Chinese children, and to provide paediatric-specific evidence for extrapolating adult dosing strategies to children.</p><p><strong>Methods: </strong>An open-label, prospective, single-arm clinical trial was conducted among eligible patients (aged <10 years old). Rifapentine concentrations and laboratory safety biomarker (total bilirubin) were analysed and used for population pharmacokinetic-toxicity model development. Simulations were performed to compare efficacy and safety of weight-based and flat-dosing strategy.</p><p><strong>Results: </strong>Once-daily rifapentine treatment was well tolerated: 310 samples (rifapentine n = 139; total bilirubin n = 171) from 36 children (age range 0.89-10 years) were captured well by a joint one-compartment pharmacokinetic with time-varying clearance and an indirect response model. The model adequately described rifapentine autoinduction, reaching a plateau after 21 days and increasing clearance by 70.4%. Simulation suggested that weight-based dosing may cause underexposure in children under 14.5 kg. A flat-dosing strategy could ensure plasma levels within the therapeutic windows. Rifapentine's impact on total bilirubin was within a 2-fold range, and the effect subsided within 5 days after discontinuation.</p><p><strong>Conclusions: </strong>Our study suggested that a flat-dosing strategy of rifapentine was potentially safe and effective for latent tuberculosis infection treatment in Chinese children aged 1 to 10 years old.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1022-1030"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408071","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":"Surveying genetic markers of antibiotic resistance and genomic background in Chlamydia trachomatis: insights from a multiplex NGS-based approach in clinical strains from Portugal.","authors":"Zohra Lodhia, Jorge Costa Da Silva, Cristina Correia, Dora Cordeiro, Inês João, Teresa Carreira, Sandra Schäfer, Elzara Aliyeva, Clara Portugal, Isabel Monge, Elsa Gonçalves, Susana Matos, Ana Paula Dias, Rita Côrte-Real, Dina Carpinteiro, Sílvia Duarte, Luís Vieira, João Paulo Gomes, Vítor Borges, Maria José Borrego","doi":"10.1093/jac/dkaf036","DOIUrl":"10.1093/jac/dkaf036","url":null,"abstract":"<p><strong>Objectives: </strong>To survey genetic markers of potential antimicrobial resistance (AMR) to macrolides and fluoroquinolones among Chlamydia trachomatis-positive samples from the collection of the Portuguese National Reference Laboratory for Sexually Transmitted Infections (STIs), and explore a multiplex PCR approach coupled with NGS to provide complementary information regarding a strain's genomic backbone.</p><p><strong>Methods: </strong>A total of 502 C. trachomatis-positive samples, mostly anorectal exudates, were subjected to PCR and sequencing of five targets, including loci potentially driving AMR (23S rRNA, gyrA and parC) and loci potentially informative about a strain's genomic backbone with emphasis on differentiation of lymphogranuloma venereum (LGV)/non-LGV and L2/L2b (a 9 bp insertion in pmpH, a 74 bp insertion upstream from CT105 and the polymorphic CT442).</p><p><strong>Results: </strong>No samples evidenced 23S rRNA mutations recognizably linked to macrolide resistance. Three samples harboured the Ser83Ile mutation in GyrA putatively driving fluoroquinolone resistance: two recombinant L2-L2b/D-Da (0.4%) and one L2 (0.2%). The screened regions in pmpH, upstream CT105 and CT442 were fully concordant with LGV/non-LGV differentiation. As expected, the pmpH L2b-specific genetic trait locus was detected in all L2b and recombinant L2-L2b/D-Da ompA genotypes, but also in 96.0% of L2 specimens, which also likely possess an L2b genomic backbone. The insertion upstream from CT105 exhibited full LGV specificity, constituting a promising target for the development of rapid LGV diagnostic assays.</p><p><strong>Conclusions: </strong>This study contributes to enhancing the knowledge of C. trachomatis molecular epidemiology, suggesting that the known genetic determinants of AMR are not disseminated in clinical C. trachomatis strains, and presents an exploratory approach that can be suitable for LGV/non-LGV and L2/L2b genomic background differentiation.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1072-1079"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441018","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":"Real-world efficacy and tolerability of CAB+RPV LA in women: addressing the gender gap in HIV treatment research.","authors":"Marta Rosas Cancio-Suárez, Ana Moreno, Santos Del Campo Terrón, María Jesús Vivancos, Alejandro G García-Ruiz De Morales, Javier Martínez-Sanz, Raquel Ron, Sofía Sánchez-Izquierdo, Manuel Vélez-Díaz-Pallarés, Santiago Moreno, María Jesús Pérez-Elías","doi":"10.1093/jac/dkaf038","DOIUrl":"10.1093/jac/dkaf038","url":null,"abstract":"<p><strong>Background: </strong>Women, particularly those of advanced age with comorbidities and polypharmacy, are often underrepresented in clinical trials evaluating long-acting (LA) antiretroviral therapy (ART) regimens like cabotegravir and rilpivirine (CAB + RPV LA). This single-center study aims to address this gap by assessing the effectiveness, tolerability, and adherence to CAB + RPV LA, focusing on women who often have complex health profiles.</p><p><strong>Methods: </strong>In this single-center, retrospective study, we analyzed virologic suppression rates, adherence and tolerability in our cohort of women living with HIV comparing their outcomes to men on the same regimen.</p><p><strong>Results: </strong>A total of 270 individuals (42 women and 228 men) were included. Women had a higher prevalence of comorbidities (86% versus 49%, P = 0.0001), and were more likely to have used ≥5 ART lines (69% versus 29%, P < 0.0001), and 31% were aged ≥60 years compared to 13% of men (P = 0.003). Despite higher rates of comorbidities and polypharmacy, women achieved virologic suppression and adherence levels comparable to men. CAB + RPV LA was well-tolerated in both groups, with no significant gender-based differences in treatment outcomes.</p><p><strong>Conclusion: </strong>CAB + RPV LA is effective and well-tolerated in women with complex ART histories, providing a viable long-acting alternative for populations traditionally underrepresented in clinical trials. These findings underscore the importance of including women in studies of novel ART regimens to ensure equitable access and outcomes.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1084-1088"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390957","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":"Prevalence of drug resistance mutations in low-level viremia patients under antiretroviral therapy in Southwestern China: a cross-sectional study.","authors":"Yuanlu Shu, Jiafa Liu, Cuixian Yang, Jianjian Li, Mi Zhang, Yuan Li, Xuemei Deng, Xingqi Dong","doi":"10.1093/jac/dkaf017","DOIUrl":"10.1093/jac/dkaf017","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to evaluate the prevalence and characteristics of drug resistance mutations (DRMs) in patients with low-level viremia (LLV) in Southwestern China, as it has become a growing challenge in AIDS clinical practice.</p><p><strong>Methods: </strong>This cross-sectional study was performed in Yunnan Province, Southwestern China. LLV was defined as 50-999 copies/mL of plasma viral load with antiretroviral therapy (ART) for at least 6 months. HIV-1 DRM detection used validated in-house protocol.</p><p><strong>Results: </strong>A total of 470 sequences were obtained, and 13 HIV-1 genotypes were identified, among which CRF08_BC (47.5%), CRF07_BC (22.3%) and CRF01_AE (10.0%) subtypes were the most prevalent. The overall prevalence of DRMs was 45.7% (215/470), and the prevalence of DRMs to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) was 39.4% (185/470), 20.6% (97/470) and 5.3% (25/470), respectively. The most common NNRTI-associated mutations were K103N (16.0%), E138A (6.6%), V179D (6.6%) and P225H (4.9%), and those in NRTIs were M184V (17.0%), D67N (3.4%) and K65R (3.0%). PI-associated mutations were infrequent, occurring in less than 1.8% of cases. The prevalence of NNRTI-associated mutations (K101E and Y188C) was found to be statistically significant among various LLV groups. Additionally, significant variations were observed in the prevalence of NNRTI-associated mutations (V106I, V106M, E138A and P225H), NRTI-associated mutation (K65R) and PI-associated mutations (L33F and Q58E) across different subtypes.</p><p><strong>Conclusions: </strong>The prevalence of DRMs in ART-experienced patients with LLV was high, and HIV-1 genotypes exhibited diversity in Yunnan Province. These findings indicate that regular DRM monitoring during LLV episodes was essential for effective clinical treatment and management in this region.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"947-954"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005907","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":"Vonoprazan improves the efficacy of bismuth quadruple therapy containing doxycycline and metronidazole as first-line Helicobacter pylori treatment in penicillin-allergic patients: a randomized controlled trial.","authors":"Tianlian Yan, Jinghua Wang, Renke Zhu, Dan Ma, Jianguo Gao, Jiewei Wang, Ye Chen, Kefang Sun, Qing Gu, Lan Li","doi":"10.1093/jac/dkae467","DOIUrl":"10.1093/jac/dkae467","url":null,"abstract":"<p><strong>Background: </strong>Helicobacter pylori eradication in penicillin-allergic patients presents challenges. Options of effective regimens are lacking in areas where tetracycline is unavailable.</p><p><strong>Objectives: </strong>To evaluate the efficacy of replacing the proton pump inhibitor (PPI) with a potassium-competitive acid blocker (P-CAB, vonoprazan) in standard bismuth quadruple therapy containing doxycycline and metronidazole as a first-line treatment for H. pylori.</p><p><strong>Methods: </strong>This prospective randomized clinical trial enrolled 332 naive patients with H. pylori infection and penicillin allergy. Participants were randomly assigned in a 1:1 ratio to either the 14 day P-CAB/BDM group (vonoprazan 20 mg twice daily, colloidal bismuth 200 mg twice daily, doxycycline 100 mg twice daily and metronidazole 400 mg three times daily) or the 14 day PPI/BDM group (rabeprazole 10 mg twice daily, and the same dose of the three other drugs as in the 14 day P-CAB/BDM group).</p><p><strong>Results: </strong>Eradication rates in the P-CAB/BDM and PPI/BDM groups were 90.4% and 71.1% (P value for superiority was 0.013), respectively, by ITT analysis. The efficacy of P-CAB/BDM remained non-inferior and even superior to PPI/BDM therapy in all ITT, modified ITT and PP analyses. The overall frequency of adverse events (39.8% and 40.4%; P = 0.911) and compliance (88.0% and 91.0%; P = 0.372) were similar between P-CAB and PPI regimens. Patients with higher body surface area were significantly associated with eradication failure in both groups (P < 0.05).</p><p><strong>Conclusions: </strong>The 14 day P-CAB/BDM therapy provided a satisfactory eradication rate of >90% (ITT analysis) and had a good safety profile as first-line H. pylori therapy, providing an alternative option for penicillin-allergic patients.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"927-934"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573032","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":"Subtypes A1 and D, and recombinant HIV-1 natural polymorphisms associated with lenacapavir drug resistance in Uganda.","authors":"Daniel Omoding, Nicholas Musinguzi, Yap Boum, Conrad Muzoora, Simone Kigozi, Peter W Hunt, Jeffrey N Martin, David R Bangsberg, Jessica E Haberer, Mark J Siedner, Suzanne M McCluskey, Guinevere Q Lee","doi":"10.1093/jac/dkaf018","DOIUrl":"10.1093/jac/dkaf018","url":null,"abstract":"<p><strong>Background: </strong>Lenacapavir, a novel HIV-1 capsid inhibitor, shows promise for treating MDR HIV-1, as well as for pre-exposure prophylaxis (PrEP) in prevention of HIV infection. Its unique mechanism and lack of cross-resistance with other antiretroviral classes make lenacapavir a significant addition to HIV therapy. The clinical trials CALIBRATE and CAPELLA have demonstrated high viral suppression rates in both ART-naive individuals and individuals with MDR HIV-1. Lenacapavir-associated resistance mutations, such as M66I and Q67H, rarely seen as natural polymorphisms in lenacapavir-naive populations, are predominantly studied in subtype B HIV-1.</p><p><strong>Objectives: </strong>Our study aimed to investigate the prevalence of lenacapavir resistance-associated mutations in HIV-1 subtypes A1 and D in a cohort of individuals living with HIV-1 from southwestern Uganda.</p><p><strong>Methods: </strong>Utilizing plasma samples from ART-naive adults living in Uganda, HIV-1 Gag p24 (capsid) sequences were analysed for lenacapavir resistance mutations.</p><p><strong>Results: </strong>Among 546 lenacapavir-naive participants, no major lenacapavir resistance-associated mutations were found. Minor mutations were present in 1.6% of participants, with T107A being the most common. Longitudinal data indicated the persistence of T107A for at least 3 years post-ART initiation in one participant. Phylogenetic analysis indicated individuals carrying T107A were found independently in distinct locations within the tree, suggesting that T107A might have arisen from multiple distinct base substitution events. Shannon entropy analysis showed high variability in certain capsid sites, but none overlapped with known lenacapavir resistance sites.</p><p><strong>Conclusions: </strong>These findings suggest a low prevalence of naturally occurring lenacapavir resistance mutations in Uganda, supporting lenacapavir's potential efficacy in this region.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"955-961"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065672","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":"Potential risk of cross-resistance to voriconazole in HIV/AIDS patients with Talaromyces marneffei infection and the mechanisms of the cross-resistance.","authors":"Yan-Qing Zheng, Qiang-Guo Li, Jean-Paul Latge, Xi-Ke Tang, Al-Odaini Najwa, Kai-Su Pan, Shi-Xiong Yang, Cun-Wei Cao","doi":"10.1093/jac/dkaf022","DOIUrl":"10.1093/jac/dkaf022","url":null,"abstract":"<p><strong>Background: </strong>The use of fluconazole for long-term oral candidiasis treatment in HIV/AIDS patients can potentially affect the clearance rate and antifungal efficacy of voriconazole against Talaromyces marneffei infection. We isolated two T. marneffei strains that were both resistant to fluconazole and voriconazole. To investigate the mechanism underlying the induction of the cross-resistance in T. marneffei.</p><p><strong>Methods: </strong>Fluconazole-resistant strains were induced in vitro. The target enzyme 14-α sterol demethylase Cyp51B was sequenced, and drug efflux pump expression was determined by RT-qPCR in all strains.</p><p><strong>Results: </strong>The sensitivity of fluconazole-induced resistant strains to fluconazole was greater than 128 mg/L, and this resistance was stably inherited after fluconazole pressure was removed. MICs of voriconazole for resistant strains were 4∼16 times greater than FRR (0.25-1 versus 0.06 mg/L). Two mutation hotspots in Cyp51B were detected: G441D and G441V. The AtrF, Mdr1 and Pmfcz genes were significantly overexpressed in the vast majority of the fluconazole-resistant strains (P < 0.05).</p><p><strong>Conclusions: </strong>The growth of T. marneffei in the presence of fluconazole could induce voriconazole resistance in vitro. The main cause of this cross-resistance in T. marneffei appears to be related to a mutation in Cyp51B at G441 and overexpression of the efflux pumps AtrF, Mdr1 and Pmfcz.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"976-979"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052534","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":"Assessing phenotypic effect of integrase strand-transfer inhibitor (INSTI)-based resistance substitutions associated with failures on cabotegravir.","authors":"Michelle L D'Antoni, Brie Falkard, Kristen Andreatta, Stephanie Cox, Cal Cohen, Christian Callebaut","doi":"10.1093/jac/dkaf019","DOIUrl":"10.1093/jac/dkaf019","url":null,"abstract":"<p><strong>Objectives: </strong>International guidelines recommend integrase strand-transfer inhibitor (INSTI)-based regimens as initial and switch therapy in people with HIV. As novel INSTIs become available, understanding how emergence of resistance at virological failures and seroconversions affects subsequent treatment options is needed. For the latest approved INSTI, cabotegravir, resistance patterns comprising Q148K/R, N155H, R263K, G118R, E138A/K and G140A/S (alone or in combination) have been documented in virological failures and seroconversions. Here, the effect of these substitutions on antiviral activity of commercially approved INSTIs, bictegravir and elvitegravir, was assessed.</p><p><strong>Methods: </strong>Antiviral testing was performed using person-derived clinical isolates (n = 52) with viral profiles similar to cabotegravir INSTI resistance patterns; susceptibility to cabotegravir, bictegravir and elvitegravir was measured using a phenotypic assay. Substitution patterns from isolates included triple [Q148K/H/R + E138A/K + G140A/C/S (n = 16)], double [Q148R + E138K (n = 3); Q148H/R + G140A/S (n = 24)] and single [N155H (n = 6); Q148R (n = 3)] resistance-associated mutations (RAMs).</p><p><strong>Results: </strong>IC50 fold changes (FCs) for triple RAMs were the highest, at 47.0, 7.59 and >144 for cabotegravir, bictegravir and elvitegravir, respectively. For cabotegravir, bictegravir and elvitegravir, respectively, mean IC50 FCs were 9.5, 2.5 and >144 for double RAMs; and 3.3, 1.4 and >65 for single RAMs. When considering clinical/biological assay cut-offs, 54% (28/52) of isolates were susceptible to bictegravir, 40% (21/52) were partially susceptible and 6% (3/52) were resistant; for elvitegravir, 100% of isolates were resistant. Cabotegravir cut-offs were not available at the time of reporting.</p><p><strong>Conclusions: </strong>Overall, clinical isolates with RAM patterns similar to clinically observed cabotegravir INSTI resistance showed meaningful increases in IC50 FCs, suggesting that cabotegravir-associated resistance may negatively affect efficacy of bictegravir- and elvitegravir-based regimens.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"962-966"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028834","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":"One day in Denmark: whole-genome sequence-based analysis of Escherichia coli isolates from clinical settings.","authors":"Ana Rita Rebelo, Valeria Bortolaia, Pimlapas Leekitcharoenphon, Dennis Schrøder Hansen, Hans Linde Nielsen, Svend Ellermann-Eriksen, Michael Kemp, Bent Løwe Røder, Niels Frimodt-Møller, Turid Snekloth Søndergaard, John Eugenio Coia, Claus Østergaard, Henrik Westh, Frank M Aarestrup","doi":"10.1093/jac/dkaf028","DOIUrl":"10.1093/jac/dkaf028","url":null,"abstract":"<p><strong>Background: </strong>WGS can potentially be routinely used in clinical microbiology settings, especially with the increase in sequencing accuracy and decrease in cost. Escherichia coli is the most common bacterial species analysed in those settings, thus fast and accurate diagnostics can lead to reductions in morbidity, mortality and healthcare costs.</p><p><strong>Objectives: </strong>To evaluate WGS for diagnostics and surveillance in a collection of clinical E. coli; to examine the pool of antimicrobial resistance (AMR) determinants circulating in Denmark and the most frequent STs; and to evaluate core-genome MLST (cgMLST) and SNP-based clustering approaches for detecting genetically related isolates.</p><p><strong>Methods: </strong>We analysed the genomes of 699 E. coli isolates collected throughout all Danish Clinical Microbiology Laboratories. We used rMLST and KmerFinder for species identification, ResFinder for prediction of AMR, and PlasmidFinder for plasmid identification. We used Center for Genomic Epidemiology MLST, cgMLSTFinder and CSI Phylogeny to perform typing and clustering analysis.</p><p><strong>Results: </strong>Genetic AMR determinants were detected in 56.2% of isolates. We identified 182 MLSTs, most frequently ST-69, ST-73, ST-95 and ST-131. Using a maximum 15-allele difference as the threshold for genetic relatedness, we identified 23 clusters. SNP-based phylogenetic analysis within clusters revealed from 0 to 13 SNPs, except two cases with 111 and 461 SNPs.</p><p><strong>Conclusions: </strong>WGS data are useful to characterize clinical E. coli isolates, including predicting AMR profiles and subtyping in concordance with surveillance data. We have shown that it is possible to adequately cluster isolates through a cgMLST approach, but it remains necessary to define proper interpretative criteria.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1011-1021"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065612","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":"rpoB mutations and their association with rifampicin resistance in clinical Staphylococcus epidermidis.","authors":"Sofie Marie Edslev, Mia Aarris, Karen Leth Nielsen, Frederik B Hertz, Thor Bech Johannesen, Camille Kolenda, Frederic Laurent, Emeli Månsson, Bo Söderquist, Marc Stegger","doi":"10.1093/jac/dkaf035","DOIUrl":"10.1093/jac/dkaf035","url":null,"abstract":"<p><strong>Background: </strong>Staphylococcus epidermidis is a ubiquitous member of the healthy skin and mucous microbiota but is also an opportunistic pathogen responsible for various infections, often treated with antibiotics like rifampicin. Resistance to rifampicin in S. epidermidis arises primarily through nonsynonymous mutations in the rpoB gene.</p><p><strong>Objectives: </strong>To investigate the prevalence of rpoB mutations and their association with phenotypic rifampicin resistance in clinical S. epidermidis isolates from Denmark, France, and Sweden.</p><p><strong>Methods: </strong>All clinical isolates (N = 942) were whole-genome sequenced to identify mutations in rpoB and subsequently linked to phenotypic rifampicin resistance based on antimicrobial susceptibility testing.</p><p><strong>Results: </strong>A total of 64 (6.8%) isolates were resistant to rifampicin. They carried all mutational changes in the rifampicin resistance-determining region (RRDR). Among 12 identified nonsynonymous mutations, 11 were exclusively observed in resistant strains, including novel mutations not previously described in S. epidermidis.</p><p><strong>Conclusions: </strong>This study highlights the diverse genetic variants of rpoB associated with rifampicin resistance in clinical S. epidermidis isolates, including novel mutations. The strong correlation between mutational changes in RRDR and phenotypic resistance reinforces the role of rpoB mutations as a primary mechanism of resistance in clinical isolates.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1067-1071"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364610","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}