Antimicrobial Agents and Chemotherapy

Culture-based monitoring of bacterial load is slow and susceptible to missing data, contributing to the length and cost of TB clinical trials. Non-culture-based alternatives, like the Tuberculosis Molecular Load Bacterial Assay (TB-MBLA), could represent a solution. Our objectives were to evaluate TB-MBLA as a biomarker in early bactericidal activity (EBA) studies and explore whether combining biomarkers with joint modelling could provide insight into underlying biological processes and reduce d...

IntroductionBuruli ulcer (BU) is a neglected tropical disease primarily affecting skin and sometimes bone. Standard therapy consists of rifampicin (RIF, once daily) plus clarithromycin (CLA, twice daily) over 8 weeks. Adding amoxicillin-clavulanate (AMX/CLV) may shorten treatment, but predicting treatment success before clinical trial implementation is challenging. AimsTo assess the probability of bacterial eradication following treatment with novel investigational BU regimens over different in...

We genotyped 1189 multidrug-resistant Mycobacterium tuberculosis isolates identified during 2013-2022 in Argentina, through a mixed strategy using PCR-based methods and whole-genome sequencing. Epidemiological, geographic distribution and microbiological data were integrated. Most cases belonged to a cluster (75.7%). The proportion of orphan and clustered cases varied across regions. The Euro-American lineage4 was virtually predominant. The most important clusters, M, Ra, Rb and Callao2 strains,...

We designed a platform model that integrates physiologically-based pharmacokinetic (PBPK) modeling with quantitative systems pharmacology (QSP) to bridge translational challenges in antibody-drug conjugate (ADC) development. The PBPK-QSP platform model was developed for the ADC trastuzumab emtansine (T-DM1) in breast cancer patients. This mechanistic framework facilitates translation across preclinical in vitro experiments, in vivo studies, and clinical trials, supporting decision-making for nov...

ContextErogothioniene (EGT), a potent natural antioxidant, exerts hepatoprotection. However, human clinical evidence remains absent. Objectiveto observe the clinical efficacy and safety studies of GeneIII(R) L-Ergothioneine Capsules in the Hepatoprotective Efficacy. Materials and methodsThirty subjects with some abnormal liver function indicators were selected to take 2 capsules of 30mg GeneIII(R) L-Ergothioneine Capsules per day, for 30 consecutive days. The changes in serum liver function bi...

Topiramate (TPM) is approved for seizures and migraine prophylaxis and is used off-label for several neuropsychiatric conditions. The available dosage forms, including tablets and sprinkle capsules, are unsuitable for patients who may be unable to take medicine orally. The resulting potential treatment interruptions could have untoward consequences and underscores the importance of developing a parenteral formulation. In this study, we developed a population pharmacokinetic model of a novel, int...

Background Antibiotic pricing is a key determinant of access and stewardship in low- and middle-income countries (LMICs), yet empirical evidence on how prices are formed within pharmaceutical markets remains limited. However, there is little longitudinal evidence on how antibiotic prices behave within national pharmaceutical supply systems. This study evaluated the patterns and determinants of systemic antibiotic pricing in Tanzania using national regulatory import permit data. Methods We conduc...

Artificial intelligence (AI), particularly large language models (LLMs), is increasingly explored in healthcare, yet its real-world usability and safety in high-risk clinical pharmacy tasks remain uncertain. Vancomycin therapeutic drug monitoring (TDM), which requires precise pharmacokinetic calculations and context-sensitive interpretation within a narrow therapeutic window, provides a stringent test case for AI-assisted decision support. This proof-of-concept study developed and evaluated a hy...

Autologous CAR-T cell therapy has demonstrated remarkable clinical efficacy in hematologic malignancies, yet its broader application remains limited by complex, labor-intensive manufacturing and inconsistent product quality. We describe a novel microfluidic cell separation platform based on Deterministic Lateral Displacement (DLD), integrated into a fully automated, closed-system instrument (Curate System), capable of processing full leukopacks in under one hour. Compared to Ficoll(R)-based dens...

Virtual clinical trials (VCTs) hold significant promise for improving the drug development process, yet their predictive reliability depends critically on design decisions that remain poorly understood. This study examines how model complexity influences VCT outcomes, as well as how the choice of prior parameter distributions and virtual patient inclusion criteria affects those outcomes. Using oncolytic virotherapy treatment of murine tumors as a case study, we compared three mathematical models...

BackgroundBiomedical Large Language Models (LLMs) combined with prompt engineering offer domain-specific reasoning, yet their application to individual-level causality assessment remains unexplored. This study evaluated five combinations of biomedical LLMs, prompting strategies, and causality algorithms by comparing their agreement with two human expert evaluators. Research design and methodsA total of 150 Individual Case Safety Reports (ICSRs) were analyzed: 140 reports from Food and Drug Admi...

Hypoglycemia is a common issue in diabetes pharmacotherapy, with seasonal variations potentially influencing its occurrence. It has been reported that blood glucose levels exhibit seasonal variation, suggesting that seasonal factors may influence the occurrence of hypoglycemia. In this study, we examined the seasonal patterns of drug-related hypoglycemia according to causative drug categories using the Japanese Adverse Drug Event Report database. We assessed a total of 545,012 adverse event repo...

BackgroundGlucagon-like peptide-1 (GLP-1) receptor agonists, including liraglutide and semaglutide, are widely prescribed to treat type 2 diabetes mellitus and obesity. Recent anecdotal reports have suggested these agents might be associated with allodynia, a neuropathic pain syndrome, but large-scale epidemiologic evidence is lacking. MethodsTo investigate this potential link, a retrospective cohort study was conducted using the IQVIA PharMetrics(R) Plus database. Adults aged 18 and older who ...

ObjectivesThe 2025 Global Consensus recommends continuing biologics throughout pregnancy in women with inflammatory bowel disease (IBD). Real-world evidence on biologic treatment patterns and outcomes remains limited. This study compared maternal and neonatal outcomes across different biologic use trajectories during pregnancy. MethodsA retrospective study was performed in pregnant women with IBD, treated and/or delivering at the University Hospitals Leuven, Belgium, between 2017 and 2025. Pati...

GLP-1 receptor agonists (GLP-1 RAs) are effective in delaying progression of chronic kidney disease in individuals with type 2 diabetes mellitus (T2DM). We evaluated whether GLP-1 RA prescription is associated with reduced nephrotoxicity in adults receiving long-term lithium therapy. We conducted a retrospective, propensity score-matched cohort study using electronic health records from the TriNetX global network, which includes de-identified data from over 127 million patients across 109 health...

Inflammatory pain is a major clinical challenge, yet appropriate human models mimicking local infection are lacking. We established a novel human pain model based on intradermal administration of lipopolysaccharide (LPS), a component of Gram-negative bacteria, and investigated the time course and underlying molecular mechanisms of inflammatory pain hypersensitivity. In a placebo-controlled pilot study with 12 healthy subjects, the intradermal LPS injection induced hyperaemia peaking at 4.5 h and...

Understanding host susceptibility to Mycobacterium tuberculosis (Mtb) is critical for the development of new vaccines. Certain individuals "resist" becoming infected with Mtb despite intensive exposure; however, it is unknown whether there is a genetic basis for "resistance" to Mtb infection across populations. Here we conducted a genome-wide association study (GWAS) of resistance to Mtb infection by carefully characterizing exposure to TB patients among 4,058 close contacts in India, Brazil, an...

BackgroundMore than 6.2 million people have died already from COVID-19. Drug resistance and relapse cases from first generation therapeutics calls for development of new drugs in alternative medicine. Complementary and Alternative Medicines (CAM) that include herbal remedies and phytochemicals are usually not fully integrated into mainstream healthcare systems. The study proposes a CAM remedy, a new polyherbal formulation NAOQ19 against the SARS-CoV-2. MethodsThe present study consists of invi...

We summarize an outbreak of N. gonorrhoeae ST16676 associated with disseminated gonococcal infections (DGIs) in Minnesota, USA in 2025. This novel strain replaced ST11184 as the predominant sequence type circulating among DGI cases in the state, encoded a porB1a allele, and carried a tetracycline resistance gene on a mobilizable plasmid.

Hospital-acquired infections are a known and growing problem worldwide. Far-UVC is a novel disinfection method that inactivates bacteria with limited penetration into human skin or eyes. A clustered, unmatched, randomized control trial (RCT) will be implemented in two Bolivian hospitals. The intervention arm will receive functioning Far-UVC lamps, whereas the control arm will receive identical lamps that do not emit UV light (shams). Based on baseline data, 40 lamp fixtures will be installed abo...