Dumitru Chesov, Maja Reimann, Tishya Mukherjee, Krishan Tewatia, Olha Konstantynovska, Aliona David, Doina Rusu, Nelly Ciobanu, Valeriu Crudu, Christoph Lange
{"title":"High rates of acquired resistance to fluoroquinolones, bedaquiline and linezolid in patients failing treatment against drug-resistant tuberculosis in the Republic of Moldova.","authors":"Dumitru Chesov, Maja Reimann, Tishya Mukherjee, Krishan Tewatia, Olha Konstantynovska, Aliona David, Doina Rusu, Nelly Ciobanu, Valeriu Crudu, Christoph Lange","doi":"10.1016/j.cmi.2025.09.003","DOIUrl":"https://doi.org/10.1016/j.cmi.2025.09.003","url":null,"abstract":"<p><strong>Objectives: </strong>Mycobacterium tuberculosis with rifampicin resistance rank among the four critical antimicrobial-resistant pathogens needing priority attention as identified by the World Health Organization (WHO) in 2024. Our objective was to identify causes of treatment failure in patients diagnosed with multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) in a nation-wide cohort in the Republic of Moldova, a WHO high-burden country of MDR/RR-TB.</p><p><strong>Methods: </strong>A retrospective cohort study analyzed national tuberculosis surveillance data (2021-2022) on patients diagnosed with MDR/RR-TB with available baseline and follow-up drug susceptibility testing for WHO Group A drugs. Treatment failure was defined as the absence of sputum culture conversion after six months. Logistic regression was used to identify risk factors associated with treatment failure.</p><p><strong>Results: </strong>Of 1034 patients initiating MDR/RR-TB treatment, 55 (5.3%) experienced treatment, failure, while 693 (67.1%) were successfully treated. Baseline resistance to WHO Group A drugs was significantly higher in patients with treatment failure than in those with successful outcomes: fluoroquinolones ((32/48 (66.7%) vs. 86/471 (18.3%), p<0.0001), bedaquiline (6/42 (12.5%) vs. 3/468 (0.6%), p<0.0001), and linezolid (12/48 (25.0%) vs. 3/468 (0.6%), p<0.0001). Acquired resistance occurred in 19/48 (39.6%) of those failing treatment but none with successful outcomes, particularly to bedaquiline 13/42 (30.9%), linezolid 6/36 (16.7%), and fluoroquinolones 4/16 (25.0%). Baseline fluoroquinolone resistance (OR 4.7, 95% CI 2.0 - 11.2) and acquired resistance to any WHO Group A drug (OR 63.5, 95% CI 7.7 - 8311.7) were associated with treatment failure.</p><p><strong>Conclusions: </strong>While frequencies of treatment failure in MDR/RR-TB are low on bedaquiline-containing treatment regimens, we find alarmingly high rates of baseline and acquired drug resistance to key second-line anti-TB drugs as a driver for treatment failure in MDR/RR-TB. Strengthening resistance monitoring, improving adherence, and optimizing individualized regimens are urgently needed to prevent the emergence of extensively drug-resistant (XDR)-TB in high-burden settings of MDR/RR-TB.</p>","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luukinen Bruno, Maarit Ahava, Aittoniemi Janne, Miikkulainen-Lahti Terhi, Pätäri-Sampo Anu
{"title":"Diagnostic performance of Xpert MTB/RIF Ultra assay with pulmonary and extrapulmonary specimens: a retrospective evaluation in a low incidence setting in Finland.","authors":"Luukinen Bruno, Maarit Ahava, Aittoniemi Janne, Miikkulainen-Lahti Terhi, Pätäri-Sampo Anu","doi":"10.1016/j.cmi.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.cmi.2025.09.002","url":null,"abstract":"<p><strong>Objective: </strong>The aim was to evaluate the sensitivity and specificity of Xpert MTB/RIF Ultra (Xpert Ultra) assay in detection of extrapulmonary tuberculosis (TB) in comparison to pulmonary TB in a low incidence setting in the Helsinki capital area of Finland.</p><p><strong>Methods: </strong>The retrospective analysis included results from 1112 pulmonary and 705 extrapulmonary samples collected between 2018 and 2023, of which 193 and 136 were culture-positive for Mycobacterium tuberculosis (MTB), respectively. Xpert Ultra results were compared to mycobacterial culture. PCR positive, culture negative cases were separately compared to available clinical data (composite reference standard, CRS).</p><p><strong>Results: </strong>Compared to culture, Xpert Ultra demonstrated 95.3% (95% CI: 91.3-97.7%) sensitivity and 94.5 % specificity (95% CI: 92.8-95.8%) with pulmonary samples, 47.1% (95% CI: 26.2-69.0%) and 96.7% (95% CI: 93.8-98.4%) with pleural fluid, 100% (95% CI: 86.9-100%) and 81.8% (95% CI: 72.4-88.6%) with tissue, 96.6% (95% CI: 81.4-100%) and 75.0% (95% CI: 62.2-84.6%) with pus, and 95.1% (95% CI: 83.0-99.5%) and 67.5% (95% CI: 51.9-80.0%) with lymph node samples, respectively. Other less common sample types were also included. When CRS was also considered, specificity exceeded 93% for all sample types. Sensitivity was 100% with both smear-positive pulmonary and smear-positive extrapulmonary samples. No false rifampicin susceptibility testing results or cross-reactivity with nontuberculous mycobacteria were detected.</p><p><strong>Conclusions: </strong>Xpert Ultra detected MTB in lymph node, tissue, and pus samples with high accuracy comparable to analysis of pulmonary samples while reducing time to diagnosis by up to several weeks compared to mycobacterial culture.</p>","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Handa Ge, Hong Cao, Jiaxin Lv, Xiao Li, Andrew Lee, Jian Zou, Minghuan Jiang, Lilong Xiao, Yong Gan, Mingwang Shen, Da Feng
{"title":"Efficacy of influenza vaccines and its relationship with immunological surrogate endpoints: a systematic review and meta-analysis of RCT.","authors":"Handa Ge, Hong Cao, Jiaxin Lv, Xiao Li, Andrew Lee, Jian Zou, Minghuan Jiang, Lilong Xiao, Yong Gan, Mingwang Shen, Da Feng","doi":"10.1016/j.cmi.2025.09.005","DOIUrl":"https://doi.org/10.1016/j.cmi.2025.09.005","url":null,"abstract":"<p><strong>Background: </strong>Vaccine efficacy may vary due to influenza strain types, their similarity, and vaccine type. The relationship between immunological surrogate endpoints and vaccine efficacy remains unclear, requiring further investigation to optimize vaccination strategies.</p><p><strong>Objective: </strong>This systematic review aims to address two key issues. First, to evaluate the vaccine efficacy stratified by vaccine types and virus strains; Second, to explore the quantitative relationship between immunological surrogate endpoints and vaccine efficacy.</p><p><strong>Data sources: </strong>We searched PubMed, Embase, and ClinicalTrials.gov databases.</p><p><strong>Study eligibility criteria, patients, interventions: </strong>We included randomized controlled trials (RCTs) published by July 16, 2024, that evaluated the efficacy of influenza vaccines against laboratory-confirmed influenza. Phase I/II clinical trials, abstracts, reviews, unregistered trials, duplicate studies, and studies lacking original data or efficacy results were excluded.</p><p><strong>Methods: </strong>This systematic review evaluates influenza vaccine efficacy and immunogenicity, including RCTs with outcomes like Geometric Mean Titer (GMT), seroprotection and seroconversion rates. Data were extracted from multiple databases and assessed using Cochrane and GRADE frameworks.</p><p><strong>Results: </strong>Twenty-six RCTs (104,931 participants) were included. Pooled vaccine efficacy against laboratory-confirmed influenza was 48.48% (95% CI: 41.9-54.29), with significant heterogeneity (I<sup>2</sup> =70.1%, p < 0.0001). IIVs had the highest vaccine efficacy (54.70%). Among different strains, the vaccine efficacy against H1N1 was the highest, reaching 59.38% (95% CI: 24.60-78.12). We found a significant non-linear relationship between Standardized Mean Difference (SMD) in Hemagglutination Antibody Titer(HAI) concentration and vaccine efficacy against symptomatic infections, but with low explanatory power, and seroconversion rates, seroprotection rates and fold increase in GMT were strongly associated with viral attack rates with Medium explanatory power (p < 0.05 for all), with explanatory values of 0.5038, 0.464, and 0.286, respectively.</p><p><strong>Conclusions: </strong>This systematic review highlights that Influenza vaccines provide moderate protection while Inactivated Influenza Vaccine demonstrate higher efficacy. Seroconversion, seroprotection rates and fold increase in GMT offer limited but valuable insights into vaccine performance. Annual vaccination is crucial for controlling both similar and dissimilar influenza strains.</p>","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Flavia Dematheis, Joseph Papaparaskevas, Erika Matuschek, Tara Wahab, Inga Fröding, Marcella Mori, Tiziano Fancello, Veronica Klausmark Jensen, Tone B Johansen, Margrete Solheim, Falk Melzer, Mandy C Elschner, Viviana Manzulli, Domenico Galante, Enrico Mantel, Roland Grunow, Gunnar Kahlmeter, Daniela Jacob, Sabine Zange
{"title":"Defining epidemiological cut-off (ECOFF) values for Brucella melitensis: An European multi-centre study.","authors":"Flavia Dematheis, Joseph Papaparaskevas, Erika Matuschek, Tara Wahab, Inga Fröding, Marcella Mori, Tiziano Fancello, Veronica Klausmark Jensen, Tone B Johansen, Margrete Solheim, Falk Melzer, Mandy C Elschner, Viviana Manzulli, Domenico Galante, Enrico Mantel, Roland Grunow, Gunnar Kahlmeter, Daniela Jacob, Sabine Zange","doi":"10.1016/j.cmi.2025.09.001","DOIUrl":"https://doi.org/10.1016/j.cmi.2025.09.001","url":null,"abstract":"<p><strong>Objectives: </strong>Brucellosis in humans is mainly caused by B. melitensis and is associated with a risk of chronic infections and relapses. For appropriate patient treatment decisions and outcomes, clinical breakpoints are needed as well as standard antimicrobial susceptibility testing (AST) procedures. In this study a Europe-wide network of Brucella reference laboratories aimed, in close collaboration with EUCAST (the European Committee on Antimicrobial Susceptibility Testing), at establishing standardized AST methods, wild-type (WT) MIC and zone diameter distributions and to set epidemiological cut-off (ECOFF) values for nine therapeutically relevant antimicrobial agents.</p><p><strong>Methods: </strong>A total of 499 B. melitensis strains were tested at six study centres by broth microdilution (BMD) and disc diffusion (DD). Minimum inhibitory concentrations (MIC) and inhibition zone diameters were curated according to EUCAST SOP 10.2 and the results were submitted to EUCAST for ECOFFs and clinical breakpoint determination.</p><p><strong>Results: </strong>BMD and DD data distributions revealed putative WT distributions for the tested antimicrobial agents. MIC ECOFFs were determined for all agents based on five to six distributions, encompassing 249-499 observations. Six isolates showed MIC values slightly above the ECOFFs, indicating the presence of potential resistance mechanism to rifampicin, streptomycin and trimethoprim-sulfamethoxazole. Zone diameter ECOFFs were established for rifampicin and ceftriaxone, while tentative (t)ECOFFs were determined for ciprofloxacin, levofloxacin, gentamicin and streptomycin.</p><p><strong>Conclusions: </strong>Standardized BMD and DD methodologies for B. melitensis were validated and AST results were used by EUCAST to set ECOFFs. Based on these, clinical breakpoints were released in v14.0 of the EUCAST clinical breakpoints table, enabling sensitive detection of resistance mechanisms and monitoring of resistance development. Genetic changes in isolates with slightly elevated MICs remain to be investigated.</p>","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Johannes Starp, Antonia Leonhardt, Michael Zoller, Christina Scharf, Johannes Zander, Michael Paal, Sebastian Greppmair, Lea M Schatz, Julian Ermtraud, Alexandra K Kunzelmann, Christina König, Jörn Grensemann, Lana Reiter, Cindy Lau, Deborah Marriott, Sophie L Stocker, Sebastian G Wicha, Uwe Liebchen
{"title":"Towards model-informed precision dosing of intravenous linezolid: a multicentre external evaluation of pharmacokinetic models in critically ill adults.","authors":"Johannes Starp, Antonia Leonhardt, Michael Zoller, Christina Scharf, Johannes Zander, Michael Paal, Sebastian Greppmair, Lea M Schatz, Julian Ermtraud, Alexandra K Kunzelmann, Christina König, Jörn Grensemann, Lana Reiter, Cindy Lau, Deborah Marriott, Sophie L Stocker, Sebastian G Wicha, Uwe Liebchen","doi":"10.1016/j.cmi.2025.08.032","DOIUrl":"https://doi.org/10.1016/j.cmi.2025.08.032","url":null,"abstract":"<p><strong>Objectives: </strong>Linezolid is a frequently utilised antibiotic to treat serious infections caused by resistant pathogens in critically ill patients. Using the currently recommended one-dose-fits-all strategy leads to insufficient target attainment. Model-informed precision dosing (MIPD), an approach combining mathematical models and therapeutic drug monitoring (TDM), can improve target attainment. The underlying population pharmacokinetic (popPK) model must be selected carefully. The aim of this study was to determine which models are applicable for MIPD in critically ill patients treated with intravenous linezolid.</p><p><strong>Methods: </strong>Data for intravenous linezolid administration was obtained from three sites and 166 patients (498 TDM samples). The predictive performance of 30 published popPK models was analysed in three scenarios: considering patients' covariates only (a priori, AP), and including one or two TDM samples (Bayesian forecasting, B1/B2). Metrics used for comparison were median relative prediction error (MDPE) [%], median absolute relative prediction error (MDAPE) [%], and the theoretical target attainment (TTA) [%] for trough concentrations of 2-8 mg/L.</p><p><strong>Results: </strong>The evaluated models were highly heterogeneous in model structure and predictive performance. MDPE, MDAPE and TTA were improved by inclusion of TDM samples. MDPE ranged from -135.9% to 110.9% (AP), -21.1% to 69.7% (B1) and -15.6% to 54.6% (B2). Overall, the lowest MDAPE was demonstrated by the models of Boak, Fang, and Wu. Several models that resulted in similarly good results are also potentially useful for MIPD.</p><p><strong>Conclusion: </strong>Predictive performance varied substantially underlining the importance of model evaluation prior to MIPD implementation for linezolid. Using the aforementioned models promises target attainment rates up to 80% in critically ill patients.</p>","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"'Hybrid and Vaccination Immunity Against Severe COVID-19 in the Post-Pandemic Era' - Author's reply.","authors":"Ilan Livne, Yair Goldberg, Amit Huppert","doi":"10.1016/j.cmi.2025.08.033","DOIUrl":"https://doi.org/10.1016/j.cmi.2025.08.033","url":null,"abstract":"","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marc Bonten, Valentijn Schweitzer, Henri van Werkhoven
{"title":"Empiric antibiotics for moderate-severe community-Acquired Pneumonia: We ought to serve patients better!","authors":"Marc Bonten, Valentijn Schweitzer, Henri van Werkhoven","doi":"10.1016/j.cmi.2025.08.029","DOIUrl":"https://doi.org/10.1016/j.cmi.2025.08.029","url":null,"abstract":"","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}