Journal of Antimicrobial Chemotherapy最新文献

{"title":"Oleanolic acid derivative bardoxolone combats multidrug-resistant Staphylococcus aureus by destroying cell membrane and pyruvate metabolism pathway.","authors":"Yun-Dan Zheng, Jiayi Xu, Jiayi Wu, Tairan Zhong, Qing-Yu He, Xuesong Sun","doi":"10.1093/jac/dkaf190","DOIUrl":"https://doi.org/10.1093/jac/dkaf190","url":null,"abstract":"<p><strong>Introduction: </strong>Staphylococcus aureus poses a significant threat to human health, making it imperative to develop novel antimicrobial agents to combat infections caused by this pathogen.</p><p><strong>Objectives: </strong>To evaluate the antibacterial efficacy and elucidate the mechanism of bardoxolone as a potential agent against multidrug-resistant S. aureus.</p><p><strong>Methods: </strong>Natural products and their derivatives were systematically evaluated for antibacterial activity. The antibacterial activity of bardoxolone was assessed in vitro against planktonic bacteria, internalized bacteria and biofilm-forming multidrug-resistant S. aureus, as well as in vivo using mouse pneumonia and thigh abscess infection models. The underlying antibacterial mechanisms were investigated through quantitative proteomics and a series of biochemical assays.</p><p><strong>Results: </strong>Bardoxolone exhibited potent antibacterial efficacy against S. aureus and other Gram-positive pathogens. It demonstrated strong antibacterial activity against internalized and biofilm-associated multidrug-resistant S. aureus, showing low resistance potential. In murine infection models, treatment significantly enhanced survival rates while reducing bacterial burden and attenuating inflammatory responses in pulmonary and femoral tissues. Mechanistic analyses revealed dual antibacterial actions: membrane integrity disruption and suppression of pyruvate metabolism, manifesting as diminished activity of pivotal enzymes, reduced acetyl-CoA/ATP synthesis and consequent growth inhibition of S. aureus.</p><p><strong>Conclusions: </strong>These findings suggest that bardoxolone holds promise as a candidate drug for treating refractory multidrug-resistant S. aureus infections.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258113","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":"Liposomal amphotericin B prophylaxis in paediatrics: a systematic review.","authors":"Emma V Thorley, Jennifer Hatch, Monica Li, Sharlene N Mashida, Elio Castagnola, Alessio Mesini, Thomas Lehrnbecher, Andreas H Groll, Adilia Warris, Laura Ferreras-Antolin","doi":"10.1093/jac/dkaf171","DOIUrl":"https://doi.org/10.1093/jac/dkaf171","url":null,"abstract":"<p><strong>Background: </strong>Liposomal amphotericin B (LAmB) is widely used for prophylaxis in paediatric patients at high risk of invasive fungal diseases (IFD) but its use is off-label and there is significant variability in dosage and frequency. This systematic review was conducted to evaluate the published data on prophylactic LAmB use in the paediatric population and to present the reported proportions of breakthrough IFD and the associated toxicity profile.</p><p><strong>Methods: </strong>EMBASE, Medline, Web of Science and the Cochrane Database were systematically searched for primary research reporting on the use of LAmB as prophylaxis for IFD in the paediatric population up to 7 December 2023, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.</p><p><strong>Results: </strong>Twenty studies, comprising three clinical trials, 12 cohort studies, two point-prevalence surveys and three pharmacokinetic (PK) studies, with 2015 patients were included. A total of 717 cases presented individual patient data. Breakthrough IFD occurred in 7.2% (49/676). The most recognized side effects were hypokalaemia in 23.2% (125/538) and derangement of liver function tests in 15.0% (49/327). Discontinuation due to toxicity occurred in 6.0% (30/503) of patients. Of the four studies reporting PK data, two examined serum levels of LAmB, one analysed CSF levels and the remaining study peritoneal levels.</p><p><strong>Conclusions: </strong>Despite widespread use of prophylactic LAmB, this systematic review highlights the paucity of paediatric data supporting its use. The heterogeneity observed in populations, dosing regimens and study design prevents conclusions being reached on its efficacy or the superiority of one dosing regimen. Overall, there is a clear need for further high-quality robust clinical data and targeted PK studies.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258112","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":"HIV-1 drug resistance among people living with HIV receiving dolutegravir-based anti-retroviral regimens in Uganda: a national laboratory-based survey using remnant viral load samples, 2022.","authors":"Christine Watera, Juliana de Fatima Da Silva, Grace Namayanja, Juliet Nkugwa Asio, Deogratius Ssemwanga, Sherri Pals, Miriam Nabukenya, Elliot Raizes, Maria Nanyonjo, Bill Elur, Esther Nazziwa, Grace Sanyu, Alisen Ayitewala, Mina Ssali, Cordelia Katureebe, Hudson Balidawa, Du-Ping Zheng, Clement Zeh, Stephanie Hackett, Christina Mwangi, Mary Naluguza, Jonathan Ntale, Edward Katongole Mbidde, Pontiano Kaleebu","doi":"10.1093/jac/dkaf180","DOIUrl":"https://doi.org/10.1093/jac/dkaf180","url":null,"abstract":"<p><strong>Background and objectives: </strong>Uganda adopted dolutegravir as its preferred HIV treatment regimen in the national guidelines for treatment of HIV and AIDS in 2018. We conducted a survey to estimate dolutegravir resistance 4 years post-dolutegravir introduction in routine clinical settings. This was a cross-sectional survey to estimate the prevalence of HIV drug resistance (HIVDR) to dolutegravir among children and adults with viral non-suppression (VNS; ≥1000 copies/mL) receiving dolutegravir-based antiretroviral therapy for at least 9 months.</p><p><strong>Methods: </strong>We used remnant specimens from routine viral load monitoring stored at Central Public Health Laboratories during February-April 2022. Genotyping of the protease, reverse transcriptase and integrase regions of the HIV-1 pol gene was done using Thermo Fisher® kits and analysed using the Stanford HIVDR database. Weighted prevalences of HIVDR with 95% confidence intervals (CI) were estimated for adults (≥15 years) and children (0-14 years).</p><p><strong>Results: </strong>We randomly selected 857 specimens including 457 from adults and 400 from children for HIVDR testing from 3578 eligible specimens collected during February-April 2022. Five hundred and eleven (59.6%) were successfully genotyped in the integrase region. Intermediate- to high-level dolutegravir HIVDR prevalence was 3.9% (CI: 0.7, 7.1) for adults and 6.6% (CI: 3.5, 9.6) for children.</p><p><strong>Conclusion: </strong>HIVDR to dolutegravir was uncommon but present among both children and adults with VNS after 9 months or more of exposure to dolutegravir. Additional longitudinal outcomes data are needed to determine if adherence counselling for patients with VNS on dolutegravir regimens might improve outcomes.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248028","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":"Four-month clofazimine regimen for susceptible pulmonary TB: a randomized clinical trial.","authors":"Nusrat Shafiq, Ashok Kumar, Vikram Vohra, Gopal Krishan Khuller, Manjula Singh, Amandeep Kaur, Narinder Gulati, Vishal Chopra, Aditi Gupta, Sandeep Kaushal, Akashdeep Singh, A N Aggarwal, Ritin Mohindra, Rajesh Raju, Honney Sawhney, Divya Goel, Alkesh Kumar Khurana, Sagar Khadanga, Ashok Bansal, Pavan Malhotra, Anil K Gupta, Dinesh Kansal, Devendra Singh Dadhwal, Sunil Sethi, Varinder K Saini, Deepak Aggarwal, Parvinder Jit Singh, Madhu Sabharwal, Lokender Kumar, Khalid Umer Khayyam, Dipti Kushwaha, Vidhu Mittal, Samriti Jain, Bharath A Chhabria, Sandeep Kaur, Abhishek Taneja, Prashant Pathak, Abhinav Gupta, Rajat Bral, Ajay Kumar, Ritika Kondel Bhandari, Avaneesh Kumar Pandey, Imraan Rather, Samir Malhotra","doi":"10.1093/jac/dkaf176","DOIUrl":"https://doi.org/10.1093/jac/dkaf176","url":null,"abstract":"<p><strong>Background: </strong>Clofazimine, an antimycobacterial agent, has demonstrated efficacy in reducing the treatment duration for MDR TB.</p><p><strong>Objectives: </strong>To determine whether a 16 week clofazimine-based regimen is non-inferior to the standard 24 week regimen for drug-susceptible pulmonary TB.</p><p><strong>Methods: </strong>CORTAIL was a multicentric, investigator-initiated, randomized controlled trial designed to assess the non-inferiority of a 16 week clofazimine-based regimen compared with the standard 24 week regimen for drug-susceptible pulmonary TB (Clinical Trials Registry of India no. CTRI/2019/03/018102). In the intervention arm, clofazimine replaced ethambutol during both the intensive and continuation phases of treatment. The primary outcome was relapse at the end of 3 month follow-up after treatment completion.</p><p><strong>Results: </strong>Across 11 centres, a total of 161 patients were randomized to the standard regimen and 161 patients received the shorter regimen. Relapse was observed in 1.9% patients in the standard group and 3.2% in the shorter regimen, the difference lying within the predefined non-inferiority margin [relative risk (RR) 1.65; 95% CI 0.444-6.19; P = 0.723; adjusted risk (AR) 1.2%; 95% CI -3.3% to 6.1%]. Key secondary outcome of relapse at 1 year was also not significantly different between the two groups (RR 1.31; 95% CI 0.58-2.95; P = 0.652; AR 1.8%; 95% CI -4.5% to 8.2%). The proportion of patients achieving sputum smear negativity (RR 1.59; 95% CI 0.69-3; P = 0.36; AR 3.1%; 95% CI -3.2% to 9.5%) and bacteriological cure (RR 1.03; 95% CI 0.57-1.88; P = 0.99; AR 0.4%; 95% CI -7.4% to 8.2%) by the end of treatment was similar between the two treatment arms.</p><p><strong>Conclusions: </strong>A clofazimine-based 16 week regimen was found to be safe and non-inferior to the currently available 24 week regimen.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234188","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":"Decreasing antimicrobial resistance in representative UK livestock species was associated with reduced total sales of antimicrobials in the last decade.","authors":"Aliya El Nagar, Tamsin C M Dewé, Fraser Broadfoot, Christopher Teale, Richard P Smith","doi":"10.1093/jac/dkaf145","DOIUrl":"https://doi.org/10.1093/jac/dkaf145","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial resistance (AMR) in pathogenic bacteria is a leading global health crisis estimated to currently contribute to human mortality on a par with malaria or HIV, with potential to increase in importance. Livestock can comprise a reservoir of AMR, which can be directly or indirectly transmitted to humans and vice versa. Representative surveillance schemes for antimicrobial use (AMU) and AMR in livestock populations have been running in the UK since 2014, during which time veterinary AMU has decreased, providing an opportunity to assess and quantify the potential relationship between AMU and AMR.</p><p><strong>Objectives: </strong>To analyse associations between the decrease of total sales of antimicrobials for livestock and the prevalence of non-wild type (WT) (AMR) Escherichia coli detected in UK pigs and poultry in 2 year weighted data points from 2014 to 2021.</p><p><strong>Methods: </strong>AMR was measured with epidemiological cut-off values (ECOFFs). Associations between prevalence of AMR, multidrug resistance (non-WT phenotypes to three or more classes of antimicrobials), (indicator measures of AMR), and standardized veterinary antimicrobial sales were modelled by regression.</p><p><strong>Results: </strong>The decrease in any detectable AMR phenotypes in E. coli (primary indicator) was associated with the decrease of total sales of antimicrobials from 59.27 mg/population correction unit (PCU) in 2014-15 to 29.14 in 2020-21 (OR: 2.69, P < 0.001). Furthermore, prevalence of E. coli displaying multidrug resistance (secondary indicator) was also associated with the decrease in sales of antimicrobials (OR: 2.58, P < 0.001).</p><p><strong>Conclusions: </strong>The decrease in sales of antimicrobials in livestock was associated with a decrease in non-WT E. coli found in livestock.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225493","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":"Lines on the line: evaluating the impact of antibiotic lock therapy versus catheter removal in the management of central vascular catheter infections.","authors":"Nischal Ranganath, Hussam Tabaja, Vaisak O Nair, Mitchell Dumais, Ryan W Stevens, Dalton Kind, Allison Lemahieu, John O'Horo, Aditya Shah","doi":"10.1093/jac/dkaf168","DOIUrl":"https://doi.org/10.1093/jac/dkaf168","url":null,"abstract":"<p><strong>Objectives: </strong>To compare the efficacy and safety of antibiotic lock therapy (ALT) versus catheter removal in managing central vascular catheter-associated bloodstream infection (CVC-BSI).</p><p><strong>Methods: </strong>We conducted a single-centre, retrospective cohort study of adult patients treated with ALT or catheter removal for management of CVC-BSI between 2018 and 2022. The primary outcome was a composite of 90 day microbiological relapse or recurrent BSI. Secondary outcomes included 30 day mortality, CVC-associated complications and Clostridioides difficile infection (CDI). Logistic regression with propensity score-adjustment was used to evaluate differences in outcomes and identify predictors of relapse.</p><p><strong>Results: </strong>During the study period, 106 participants received ALT and 181 underwent catheter removal. Patients treated with ALT received shorter courses of systemic antimicrobials (11 versus 14 days; P < 0.001) and had shorter hospital stays (4 versus 10 days; P < 0.001). Median duration of catheter salvage in patients receiving ALT was 28 days (IQR 7-80). Primary composite outcome was similar between both groups, but ALT was associated with a significantly higher risk of microbiological relapse within 90 days (20% versus 7%; adjusted odds ratio 3.93, 95% CI 1.64-9.40; P = 0.002). No significant difference in 30 day mortality, CVC-related complications or CDI was observed. CoNS BSI was an independent predictor of microbiological relapse in patients treated with ALT (OR 2.28; P = 0.05).</p><p><strong>Conclusions: </strong>Although ALT offers a non-invasive catheter salvage strategy, its association with higher relapse rates, particularly in CoNS BSI, suggests catheter removal should remain the preferred approach when feasible. ALT could be considered a short-term catheter salvage strategy for pathogens with low virulence when used with close surveillance.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225496","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":"Gut microbiota and weight gain in people with HIV on integrase inhibitors: a five-year longitudinal study.","authors":"Javier García-Abellán, José A García, Ronald Galdámez, María José Gosalbes, Marta Fernández-González, Sergio Padilla, Paula Mascarell, Guillermo Telenti, Félix Gutiérrez, Mar Masiá","doi":"10.1093/jac/dkaf182","DOIUrl":"https://doi.org/10.1093/jac/dkaf182","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the relationship between the gut microbiota composition and significant weight gain in virologically-suppressed people with HIV (PWH) on antiretroviral therapy.</p><p><strong>Methods: </strong>This 5-year prospective longitudinal study included virologically-suppressed PWH receiving regimens based on the integrase strand transfer inhibitors (INSTIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs). Body weight was measured annually, with significant weight gain defined as a ≥10% increase between consecutive measurements or compared to baseline. Gut microbiota profiling was conducted using 16S rRNA sequencing (V3-V4 regions) via the Illumina MiSeq platform.</p><p><strong>Results: </strong>202 participants were recruited, with 169 completing the 240-week follow-up. Among these, 63 remained on INSTI-based, 79 on NNRTI-based and 27 on NNRTI + INSTI-based regimens. Median (interquartile range (IQR)) 5-year weight gain was 1.3 (-2.8 to 4.5) kg. Significant weight gain occurred in 70 (34.7%) participants, including 20 (9.9%) with ≥10% gain between consecutive measurements and 50 (24.8%) from baseline. No significant differences were observed in adjusted α- and β-diversity indices between groups defined by weight gain. Adjusted analysis of compositions of microbiomes with bias correction 2 model showed that weight gain was associated with the genera Dialister and Tyzzerella_4, whereas Phascolarctobacterium was enriched in those without significant weight gain. While overall weight gain did not differ between INSTI-based and NNRTI-based groups, participants on INSTIs-based regimens showed higher relative abundances of bacteria linked to weight gain, like Tyzzerella_4 (0.05% versus 0.02%, P = 0.017) and Lactobacillus (0.29% versus 0.22%, P = 0.009).</p><p><strong>Conclusions: </strong>Significant weight gain in the PWH is associated with distinct gut microbiota profiles. The enrichment of weight gain-associated taxa, such as Tyzzerella_4 and Lactobacillus, in individuals on INSTI-based regimens suggests a potential microbiota-mediated mechanism modulating metabolic outcomes.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225495","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":"Five-days-on-two-days-off (FOTO) versus daily bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed people with HIV: a pilot randomized clinical trial.","authors":"Hsin-Yun Sun, Ya-Ting Lin, Wen-Chi Chang, Wen-Chun Liu, Yi-Ching Su, Ching-Hua Kuo, Chien-Ching Hung","doi":"10.1093/jac/dkaf186","DOIUrl":"https://doi.org/10.1093/jac/dkaf186","url":null,"abstract":"<p><strong>Objectives: </strong>This open-label, randomized clinical trial determined plasma bictegravir trough concentration (Ctrough) and compared virological efficacy with daily bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) versus BIC/FTC/TAF taken five-days-on-two-days-off (FOTO) in people with HIV (PWH).</p><p><strong>Methods: </strong>Sixty PWH aged ≥20 years with plasma HIV RNA load (PVL) of <50 copies/mL for ≥6 months after having received daily BIC/FTC/TAF were randomized (1:1) to daily versus FOTO BIC/FTC/TAF. The primary endpoint was plasma bictegravir Ctrough above the in vitro protein-adjusted 95% effective concentration (162 ng/mL) at Weeks 4, 28 and 52. The secondary endpoints were PVL < 50 copies/mL and weight and renal and metabolic parameters at the same time points. After Week 52, all participants entered the 48-week extension phase to receive FOTO BIC/FTC/TAF.</p><p><strong>Results: </strong>There were no significant differences in the baseline clinical characteristics, including drug-metabolizing gene polymorphisms, between the two groups. In the FOTO group, 90%, 93.3% and 100% of participants achieved a bictegravir Ctrough of >162 ng/mL at Weeks 4, 28 and 52, respectively. In intention-to-treat analysis, PVL of <50 copies/mL at Weeks 4, 28 and 52 was achieved by 100%, 93.3% and 100%, respectively, in the FOTO group, compared with 96.7%, 93.3% and 96.7% in the daily group. All five participants in the FOTO group with bictegravir Ctrough of <162 ng/mL at Weeks 4 and 28 maintained PVL <50 copies/mL. Of 57 (95.0%) participants who entered the extension phase, 56 (98.2%) completed the study and all maintained PVL <50 copies/mL at extension Week 48.</p><p><strong>Conclusions: </strong>We showed PWH could successfully maintain sufficient bictegravir exposure and virological suppression with FOTO BIC/FTC/TAF.</p><p><strong>Clinical trials registration: </strong>NCT06773754.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225494","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":"A novel azithromycin resistance mutation in Mycoplasma genitalium induced in vitro.","authors":"Teck-Phui Chua, Jennifer Danielewski, Catriona S Bradshaw, Dorothy A Machalek, Suzanne M Garland, Jose L Huaman, Jørgen S Jensen, Gerald L Murray","doi":"10.1093/jac/dkaf174","DOIUrl":"https://doi.org/10.1093/jac/dkaf174","url":null,"abstract":"<p><strong>Background: </strong>Mycoplasma genitalium is a sexually transmitted bacterium of increasing concern due to issues around antimicrobial resistance. Resistance is typically mediated by SNPs; however, the difficulty of isolation and culture of M. genitalium limits the ability to analyse the impact of individual mutations.</p><p><strong>Objectives: </strong>The aim of this study was to generate and characterize antibiotic-resistant M. genitalium mutants in vitro to understand the development of macrolide resistance in this bacterium.</p><p><strong>Methods: </strong>Sequential MIC assays for azithromycin were performed using the laboratory strain of M. genitalium (G37) grown in Hayflick medium. Bacteria were enumerated by droplet digital PCR (ddPCR) targeting mgpB, and a new ddPCR assay was established to detect specific mutations in the 23S rRNA gene. MICs of selected macrolide antibiotics were determined in Hayflick medium. Whole genome sequencing (WGS) was performed on the Oxford Nanopore MinION.</p><p><strong>Results: </strong>After eight passages in azithromycin, a novel 23S rRNA gene mutation, G2057A (Escherichia coli numbering), was detected. The mutant did not display a detectable growth defect and had elevated MICs to azithromycin (8-fold), josamycin (8-fold) and erythromycin (16- to 32-fold). WGS did not identify other mutations likely to contribute to reduced macrolide susceptibility.</p><p><strong>Conclusions: </strong>A novel 23S rRNA gene mutation was identified in M. genitalium. This variation is found in Mycoplasma hominis, which is intrinsically resistant to certain macrolides. While this mutation has not been observed clinically in M. genitalium, these findings have expanded our understanding of resistance mechanisms within the Mollicutes, in particular the propensity for M. genitalium to develop resistance, even in low concentrations of antibiotic, and the interaction of azithromycin with the ribosome.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215907","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":"Dalbavancin as chronic suppressive therapy in a patient undergoing monthly apheresis: a case report with therapeutic drug monitoring.","authors":"Carlo Pallotto, Margherita Albagini, Antonio D'Avolio, Alice Palermiti, Laura Curci, Daniela Francisci","doi":"10.1093/jac/dkaf173","DOIUrl":"https://doi.org/10.1093/jac/dkaf173","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208533","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}