International Journal of Antimicrobial Agents最新文献

{"title":"LightCPPgen: An Explainable Machine Learning Pipeline for Rational Design of Cell Penetrating Peptides.","authors":"Gabriele Maroni, Filip Stojceski, Lorenzo Pallante, Marco A Deriu, Dario Piga, Gianvito Grasso","doi":"10.1016/j.ijantimicag.2025.107611","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107611","url":null,"abstract":"<p><p>Cell-penetrating peptides (CPPs) are powerful vectors for the intracellular delivery of a diverse array of therapeutic molecules. Despite their potential, the rational design of CPPs remains a challenging task that often requires extensive experimental efforts and iterations. In this study, we introduce an innovative approach for the de novo design of CPPs, leveraging the strengths of machine learning (ML) and optimization algorithms. Our strategy, named LightCPPgen, integrates a LightGBM-based predictive model with a genetic algorithm (GA), enabling the systematic generation and optimization of CPP sequences. At the core of our methodology is the development of an accurate, efficient, and interpretable predictive model, which utilizes 20 explainable features to shed light on the critical factors influencing CPP translocation capacity. The CPP predictive model works synergistically with an optimization algorithm, which is tuned to enhance computational efficiency while maintaining optimization performance. The GA solutions specifically target the candidate sequences' penetrability score, while trying to maximize similarity with the original non-penetrating peptide in order to retain its original biological and physicochemical properties. By prioritizing the synthesis of only the most promising CPP candidates, LightCPPgen can drastically reduce the time and cost associated with wet lab experiments. In summary, our research makes a substantial contribution to the field of CPP design, offering a robust framework that combines ML and optimization techniques to facilitate the rational design of penetrating peptides, by enhancing the explainability and interpretability of the design process.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107611"},"PeriodicalIF":4.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033379","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":"Results of TOR001: An open-label single patient study using targeted bacteriophage therapy for the treatment of a chronic urinary tract infection","authors":"Jonathan D. Cook ,&nbsp;Payton B. Hooey ,&nbsp;Keiko C. Salazar ,&nbsp;Justin R. Clark ,&nbsp;Umesh Jain ,&nbsp;Carlos Fernando ,&nbsp;Hanjeong Harvey ,&nbsp;Alexander Cervantes ,&nbsp;Stephanie Omagari ,&nbsp;Udi Blankstein ,&nbsp;Andrew M. Kropinski ,&nbsp;Alan R. Davidson ,&nbsp;Karen L. Maxwell ,&nbsp;Lori L. Burrows ,&nbsp;Austen L. Terwilliger ,&nbsp;Anthony W. Maresso ,&nbsp;Greg J. German","doi":"10.1016/j.ijantimicag.2025.107613","DOIUrl":"10.1016/j.ijantimicag.2025.107613","url":null,"abstract":"<div><div>Chronic urinary tract infections are persistent bacterial infections with the potential to drive antibiotic resistance. Like other persistent bacterial infections, intracellular bacterial reservoirs and biofilm formation hinder the clearance of pathogens despite long courses of antibiotic therapy. New strategies for treatment of these persistent infections are needed.</div><div>Here we describe the results of an open-label individual patient study using bacteriophage therapy to treat a chronic urinary tract infection in an immunocompetent 72-year-old woman without underlying urolithiasis or indwelling devices. We co-administered HP3.1, HP3, and ES19 bacteriophages with demonstrated <em>in vitro</em> activity via bladder instillation, orally, and as a topical formulation.</div><div>The primary outcome was safety and tolerability of the treatment. Adverse events were monitored through daily symptom logs and laboratory analysis of blood samples obtained throughout the study. We found that the treatment was safe and well tolerated with no serious adverse events reported. No adverse events were deemed related to the study material. The secondary outcomes were clinical and microbiological efficacy as monitored through daily symptom logs and standard urine culture, respectively. Two weeks after initial clinical improvement, her condition relapsed and culture was consistent with previous isolates. Treatment with ertapenem following bacteriophage therapy led to sustained clinical and microbiologic cure. Exploratory analysis through whole genome sequencing of pre- and post-treatment isolates identified mutations in genes associated with adhesion and evasion that may influence virulence and promote clearance.</div><div>These results inform expanded randomized clinical trials and support the growing literature that bacteriophage therapies are safe and effective.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107613"},"PeriodicalIF":4.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033323","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":"The prospect of approved and commercially available phage therapeutics","authors":"Harald König","doi":"10.1016/j.ijantimicag.2025.107612","DOIUrl":"10.1016/j.ijantimicag.2025.107612","url":null,"abstract":"<div><div>As antibiotic resistance of bacterial pathogens spreads, interest in bacteriophage (phage) therapy has soared again in many countries. Currently, there is no phage therapeutic with marketing approval and phage treatments are relegated to few patients, mostly under compassionate use schemes when approved drugs failed or are unavailable. Commercially manufactured and approved phage preparations could both expand the availability of therapeutic phages for existing, exemptional treatment schemes and result in more broadly usable phage therapeutics with marketing authorization. The lack of clinical evidence from modern clinical trials and issues with the patenting of phages are often seen as important challenges toward commercially produced and approved therapeutic phages. Here, an analysis of available data suggests that while a surge in patent filings and new clinical trials by biotech companies has begun and these challenges may be surmountable, the long-term success of commercial phage therapeutics will hinge on policy solutions that address post-approval regulatory and economic barriers.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107612"},"PeriodicalIF":4.6,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023308","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":"Cross-border dialogue: An international survey of regulators on phage therapy.","authors":"Riley D Alvarez, Christine Årdal, Annika Y Classen, Tobi E Nagel, Pieter-Jan Ceyssens, Greg J German","doi":"10.1016/j.ijantimicag.2025.107614","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107614","url":null,"abstract":"<p><p>With antimicrobial resistance as a worldwide public health concern, bacteriophage (phage) therapy (PT) may help treat bacterial infections. However, given its particularities compared with traditional small molecule drugs, there are variations in how it is regulated worldwide. Regulators are key players governing PT, yet their perspectives have been largely unexplored. Here, we present findings from the first international survey aimed at capturing the current and future landscape of PT according to regulators. We distributed the survey to members of the second European Union-Joint Action on Antimicrobial Resistance and Healthcare-Associated Infections and individually contacted regulators. Results were collected between October 30, 2024 and March 26, 2025. Twenty-three respondents represented twenty-one countries across Europe, North America, Africa, and Oceania (response rate 67%). Phages or PT were reported as being mentioned in only three national action plans (13%). Nearly half of the respondents declared no prior involvement in phage-related regulatory processes in the past decade, and 32% were uncertain if phages have ever been used therapeutically in their country. Among those who were aware of previous in-country PT, single-use cases dominated, with 27% of respondents acknowledging this as a resource burden (compared to other regulatory applications). Some regulators reported that adapted frameworks are being explored for PT, while one indicated a new framework was being considered. These results underscore that globally major steps aimed at increasing awareness, engagement, and collaboration on best practices amongst regulators are still required to clarify and improve clinical access pathways for PT.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107614"},"PeriodicalIF":4.6,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023221","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":"Optimizing linezolid dosing for nosocomial urinary tract infections in critically ill patients with renal impairment","authors":"Adela Benítez-Cano ,&nbsp;Xin Liu ,&nbsp;Haiping Xu ,&nbsp;Xinyi Tang ,&nbsp;Luigi Zattera ,&nbsp;Daniel Fresan ,&nbsp;Luisa Sorlí ,&nbsp;Jesús Carazo ,&nbsp;Isabel Ramos ,&nbsp;Ramón Adalia ,&nbsp;Juan Pablo Horcajada ,&nbsp;Nuo Xu ,&nbsp;Wenyao Mak ,&nbsp;Xiaoqiang Xiang ,&nbsp;Julia Miedes-Aliaga ,&nbsp;Cristina Bosch ,&nbsp;Elena Colominas-González ,&nbsp;Sonia Luque ,&nbsp;Xiao Zhu","doi":"10.1016/j.ijantimicag.2025.107610","DOIUrl":"10.1016/j.ijantimicag.2025.107610","url":null,"abstract":"<div><h3>Background</h3><div>This study characterized the urinary pharmacokinetics and pharmacodynamics (PK/PD) of linezolid (LNZ) in critically ill patients with renal impairment and nosocomial multidrug-resistant Gram-positive urinary tract infections (UTIs). The aim was to address therapeutic challenges arising from limited treatment options and uncertain urinary excretion, to establish optimized dosing strategies.</div></div><div><h3>Methods</h3><div>A prospective observational study was conducted in ICU patients with renal impairment. LNZ plasma and urine concentration and urine volume were analyzed to develop semi-mechanistic population PK model. Simulations evaluated dosing regimens based on PK/PD target (AUC₂₄/MIC ≥ 80) and toxicity threshold (C_ss,min ≥ 8 mg/L).</div></div><div><h3>Results</h3><div>A plasma/bladder urine joint model described PK in 20 critically ill patients (median age 85, APACHE-II 20) using 398 plasma/urine samples. Estimated clearances: non-renal (CL_NR) 4.9 L/h, renal (CL_R) 0.261 L/h, urine (CL_U) 0.062 L/h. Renal excretion accounted for 5% of the dose at eGFR 30 mL/min/1.73m². Urinary LNZ exposure increased with eGFR; age significantly increased plasma exposure. Simulations indicated 600 mg Q12h achieved sufficient urinary exposure for eGFR 15–60 mL/min/1.73m², but not for eGFR &lt;15 mL/min/1.73m². Lower eGFR correlated with higher plasma toxicity risk.</div></div><div><h3>Conclusions</h3><div>Renal function was positively associated with LNZ urinary exposure. The standard LNZ 600 mg Q12h was appropriate for treating UTIs in renal impairment patients, except for those with eGFR &lt;15 mL/min/1.73 m². The use of extended infusion may help mitigate the risk of toxicity while maintaining urinary exposure.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107610"},"PeriodicalIF":4.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015193","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":"Model-informed precision dosing of vancomycin in Chinese adult patients receiving renal replacement therapy: Systematic evaluation of published pharmacokinetic models and dosing regimen simulations","authors":"Ping Yang ,&nbsp;Huifang Zhang ,&nbsp;Mengting Chen ,&nbsp;Wanqiu Yang ,&nbsp;Fangqing Zhou ,&nbsp;Yuancheng Chen ,&nbsp;Ruilan Wang ,&nbsp;Hailan Wu ,&nbsp;Yan Chen ,&nbsp;Beining Guo ,&nbsp;Xiaofen Liu ,&nbsp;Yaxin Fan ,&nbsp;Jing Zhang","doi":"10.1016/j.ijantimicag.2025.107608","DOIUrl":"10.1016/j.ijantimicag.2025.107608","url":null,"abstract":"<div><h3>Objectives</h3><div>The pharmacokinetics of renally cleared vancomycin are significantly altered in critically ill patients undergoing renal replacement therapy (RRT), affecting the achievement of therapeutic targets. We evaluated the predictive performance of RRT patient-based PopPK models for model-informed precision dosing and subsequently simulated optimal dosing regimens for this population.</div></div><div><h3>Methods</h3><div>Six adult PopPK models were systematically identified and evaluated using a dataset of 226 concentrations from 23 adult patients on RRT from two study centers. Predictive performance was assessed using simulation and prediction-based diagnostics for a priori dosing based on patient characteristics and Bayesian dosing incorporating more than one measured trough concentration.</div></div><div><h3>Results</h3><div>The Oda model showed the best performance in prediction-based evaluation, with a median prediction error of –8.4%. Bayesian forecasting incorporating at least one measured trough concentration improved predictive capability, and the inclusion of dialysis filter characteristics in the model may further enhance its performance. For a 70 kg patient under this scenario: A 1 g loading dose during the first dialysis session achieves target concentrations within 24–48 h. Subsequent 0.5 g maintenance dose should be administered post-dialysis. Dose escalation is required for extended dialysis sessions (≥12 h).</div></div><div><h3>Conclusion</h3><div>The Oda model demonstrated the best predictive capability for dose prediction among the tested models in Chinese adult patients receiving RRT. However, its F20 and F30 values were undershot compared to the standard external evaluation criteria of F20 ≥35% and F30 ≥50%, highlighting the need for further study to optimize the model or collect additional data to validate its performance.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107608"},"PeriodicalIF":4.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006202","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":"Extraintestinal pathogenic Escherichia coli (ExPEC) O-serotype distribution and antibiotic resistance profiles among the aging population in China: A longitudinal, multi-center study","authors":"Renru Han ,&nbsp;Chengkang Tang ,&nbsp;Feng Yu ,&nbsp;Ting Li ,&nbsp;Siquan Shen ,&nbsp;Li Ding ,&nbsp;Weiwei Yang ,&nbsp;Qingyu Shi ,&nbsp;Yang Yang ,&nbsp;Shi Wu ,&nbsp;Dandan Yin ,&nbsp;Yan Guo ,&nbsp;Fupin Hu ,&nbsp;China Antimicrobial Surveillance Network (CHINET) Study Group","doi":"10.1016/j.ijantimicag.2025.107607","DOIUrl":"10.1016/j.ijantimicag.2025.107607","url":null,"abstract":"<div><h3>Objective</h3><div>Extraintestinal pathogenic Escherichia coli (ExPEC) is a leading cause of community-acquired bacteremia and sepsis, which contributes to the substantial burden of invasive E. coli disease (IED) in older adults. This study aimed to estimate the O-serotype distribution of blood and sterile site ExPEC among older adults in China and the characteristics of antimicrobial resistance, O-serotypes, and O genotypes.</div></div><div><h3>Methods</h3><div>A total of 499 non-duplicated clinical isolates of E. coli derived from sterile body fluids from subjects aged ≥ 60 years from 55 medical institutions participating in the CHINET from different regions of China from 2016 to 2022 were collected. Antimicrobial susceptibility testing and whole genome sequencing (WGS) were performed for all isolates. For isolates with an O genotype pertaining to ExPEC9V (a group of 9 O-serotypes with high prevalence among bloodstream infections globally), an agglutination assay was conducted for validation.</div></div><div><h3>Results</h3><div>In this study, 82.2 % and 10.7 % of ExPEC isolates were tested as multidrug-resistant (MDR) and carbapenem-resistant E. coli (CREC), respectively. WGS revealed diverse STs and phylogroups. The most prevalent O serotypes were O25 (14.2 %), O75(6.2 %), O1(5.6 %), O6(4.6 %), O15(3.8 %), O45(3.6 %), O101(3.4 %), O11(3.4 %), O153(3.4 %), O8(3.4 %), O2/O50(3.0 %), and O9/O9a(3.0 %). Among MDR isolates, O25 was the dominant O serotype. 40.1 % of isolates were identified as ExPEC9V.</div></div><div><h3>Conclusions</h3><div>In conclusion, O25 is the most prevalent O serotype among ExPEC isolates. The ExPEC9V O-serotype prevalence is generally consistent across MDR and different sexes.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107607"},"PeriodicalIF":4.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000452","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":"Population pharmacokinetics and pharmacodynamics of eravacycline in patients with complicated intra-abdominal infections and community acquired bacterial pneumonia: Support for a fixed-dose treatment regimen","authors":"Yuancheng Chen ,&nbsp;Xiaojie Wu ,&nbsp;Size Li ,&nbsp;Jicheng Yu ,&nbsp;Yi Jin ,&nbsp;Jufang Wu ,&nbsp;Shuyan Yu ,&nbsp;Jufang Shen ,&nbsp;Jianzhong Tang ,&nbsp;Yaoxuan Fu ,&nbsp;Xu Zhu ,&nbsp;Jing Zhang","doi":"10.1016/j.ijantimicag.2025.107603","DOIUrl":"10.1016/j.ijantimicag.2025.107603","url":null,"abstract":"<div><div>Eravacycline is a tetracycline used for the treatment of complicated intra-abdominal infections (cIAI) and has the potential to treat community-acquired bacterial pneumonia (CABP). The approved regimen for cIAI is 1 mg/kg (Q12h). However, studies have reported the inconvenience of drug preparation based on body weight (BW) and wastage of the drug, because the specification is 50 mg per vial. A fixed-dose regimen based on population pharmacokinetic/pharmacodynamic (PK/PD) modeling and simulations may address these limitations. Three clinical trials were performed in healthy Chinese participants and patients with cIAI and CABP. A PopPK model was developed using nonlinear mixed-effects modeling. A fixed-dose regimen in patients with a BW of 40–175 kg was recommended by the Monte Carlo simulation. The probability of target attainment and the cumulative fraction of response (CFR) were calculated. Overall, 79 participants were included in the study. BW, sex, albumin level, and subject type were covariates on PK. When patients received a fixed-dose, AUC_0-12 _h,ss was 80–125% in patients with BW 60 kg receiving 1 mg/kg eravacycline. The PK/PD cutoff and CFR for the fixed-dose regimens were close to those of 1 mg/kg. The recommended fixed-doses (body weight range) were 50 mg (40–60 kg), 75 mg (60–100 kg), 100 mg (100–125 kg), 125 mg (125–150 kg), and 150 mg (150–175 kg). This should be used with caution in patients with BW &gt;137 kg because the actual PK data were not collected. Nonetheless, fixed dosing is more convenient for drug preparation, avoids drug waste, and reduces medical costs compared with weight-based dosing.</div><div>Trial Registration Number: ChiCTR1900022906, ChiCTR1900022060, and ChiCTR2200055666.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107603"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992434","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":"Evaluation of the Roche cobas MTB and MTB-RIF/INH for detecting Mycobacterium tuberculosis complex and resistance to isoniazid and rifampicin: A prospective, multicenter diagnostic accuracy study","authors":"Shun-Chung Hsueh ,&nbsp;Chieh-Lung Chen ,&nbsp;Chang-Ru Lin ,&nbsp;Hsiu-Hsien Lin ,&nbsp;Tai-Fen Lee ,&nbsp;Kun-Hao Tseng ,&nbsp;Hsueh-Wei Chu ,&nbsp;Chin-Li Lee ,&nbsp;Wei-Yu Hsu ,&nbsp;Yu-Tsung Huang ,&nbsp;Chih-Hao Chen ,&nbsp;Mao-Wang Ho ,&nbsp;Ruwen Jou ,&nbsp;Jung-Yien Chien ,&nbsp;Po-Ren Hsueh","doi":"10.1016/j.ijantimicag.2025.107605","DOIUrl":"10.1016/j.ijantimicag.2025.107605","url":null,"abstract":"<div><h3>Objectives</h3><div>To evaluate the diagnostic performance of Roche cobas MTB and MTB-RIF/INH assays for detecting <em>Mycobacterium tuberculosis</em> complex (MTBC) and resistance to isoniazid (INH) and rifampicin (RIF).</div></div><div><h3>Methods</h3><div>This multicentre study was conducted in Taiwan between September 2023 and June 2024. Clinical specimens were collected from adult patients with presumptive tuberculosis (TB). All samples underwent acid-fast staining, culture, Xpert MTB/RIF Ultra assay and cobas MTB assays. The MTB-RIF/INH assay was conducted as a reflex test for specimens that tested positive with the cobas MTB assay. Thirty-seven MTBC control strains from the Taiwan Centers for Disease Control (TCDC) were also analysed to assess drug resistance detection. Whole genome sequencing was used to resolve discrepancies with phenotypic drug susceptibility testing (pDST).</div></div><div><h3>Results</h3><div>A total of 425 clinical samples from 378 adult patients were analysed. Among 392 respiratory samples, 53 were culture-positive for MTBC. cobas MTB showed 98.1% sensitivity (95% confidence interval [CI], 89.9%–100%) and 95.9% specificity (95% CI, 93.2%–97.7%) for MTBC detection. Drug resistance detection was evaluated using 37 TCDC stains. For RIF resistance, the cobas MTB-RIF/INH assay correctly identified all 11 phenotypically resistant strains. Among the 26 phenotypically susceptible strains, 25 were correctly identified, with 1 false-positive result (overall accuracy: 97.3%). For INH resistance (0.2 µg/mL), the assay identified 16 resistant and 19 susceptible strains, with 2 false negatives (accuracy: 94.6%).</div></div><div><h3>Conclusions</h3><div>Roche cobas MTB and MTB-RIF/INH assays demonstrated high accuracy for detecting MTBC and drug resistance, supporting their use as reliable diagnostic tools in clinical practice.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107605"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992405","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 Single Amino acid in PBP1a drives high-level penicillin and amoxicillin resistance in streptococcus suis","authors":"Zeren Peng ,&nbsp;Jianping Wang ,&nbsp;Shun Kang ,&nbsp;Sixiang Xu ,&nbsp;Hongkun Zhuang ,&nbsp;Jinlu Zhu ,&nbsp;Huochun Yao ,&nbsp;Han Zheng ,&nbsp;Zongfu Wu","doi":"10.1016/j.ijantimicag.2025.107604","DOIUrl":"10.1016/j.ijantimicag.2025.107604","url":null,"abstract":"<div><div><em>Streptococcus suis</em> is an important zoonotic pathogen that causes severe diseases in both humans and pigs, with β-lactam antibiotics serving as the primary treatment. However, resistance to penicillin and amoxicillin has been steadily increasing, and the mechanisms underlying their resistance remain poorly understood. In this study, we analyzed 534 <em>S. suis</em> strains collected from diseased and healthy pigs in China between 2005 and 2024. Among them, 123 strains exhibited high-level resistance to penicillin (minimum inhibitory concentration (MIC) ≥8 µg/mL), and 78 also displayed co-resistance to amoxicillin. Amino acid sequence alignment of penicillin-binding proteins (PBPs), molecular docking, acylation efficiency assays, site-directed mutagenesis, and MIC testing revealed that the S695A mutation in PBP1a significantly reduces its binding affinity to penicillin and amoxicillin, contributing to high-level resistance. Substituting alanine (A) with serine (S) at position 695 in the highly resistant <em>S. suis</em> strain YS682 resulted in a 64-fold reduction in penicillin resistance (MIC decreased from 128 µg/mL to 2 µg/mL) and a 16-fold reduction in amoxicillin resistance (MIC decreased from 32 µg/mL to 2 µg/mL). Furthermore, 95.56% (366/383) of penicillin-susceptible strains carried S at position 695 of PBP1a. This study provides new insights into the molecular mechanisms driving penicillin and amoxicillin resistance in <em>S. suis</em>.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107604"},"PeriodicalIF":4.6,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953167","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}