Antimicrobial Agents and Chemotherapy

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...

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...

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...

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...

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...

BackgroundGabapentin prescriptions have increased 123% since 2010, reaching 15.5 million Americans annually. Recent studies suggest gabapentin-dementia associations, but whether concomitant medications modify this risk is unknown. Both gabapentin and calcium channel blockers (CCBs) affect neuronal calcium signaling through distinct mechanisms, raising the possibility of pharmacodynamic interaction. MethodsActive comparator new-user cohort study using Rutgers Clinical Research Data Warehouse (20...

BackgroundPreoperative biliary stenting alters biliary colonization and may reduce the effectiveness of perioperative antibiotic prophylaxis in pancreatoduodenectomy. Although broader-spectrum regimens have been associated with improved infectious outcomes, their microbiological adequacy in routine clinical practice remains poorly defined. We therefore evaluated the real-world adequacy of a prolonged ampicillin-sulbactam protocol, its association with infectious outcomes and survival, and the po...

Human genetics has become a cornerstone of drug target discovery, yet the value of Mendelian randomization (MR) for predicting clinical success remains uncertain. Here, we systematically evaluated MR across 11,482 target-indication pairs with documented Phase II clinical outcomes to assess its utility for drug development. We find that MR statistical significance alone does not enrich for Phase II success, in contrast to genome-wide association study (GWAS) support, which confers an increase in ...

BackgroundHospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP), particularly those caused by multi-drug resistant organisms (MDROs), often require newer antibiotic treatment. The efficacy and safety of newer antibiotics compared to generic antibiotics in randomized controlled trials (RCTs) have not been evaluated before. MethodsIn this systematic review, we searched RCTs in the United States National Library of Medicine (PubMed), Cochrane Central Reg...

BackgroundSpatial emanators disrupt mosquito behaviour by inducing movement away from chemical stimuli and interfering with host detection and feeding. These tools were recently endorsed by the World Health Organization (WHO) for malaria control, based largely on clinical evidence from East Africa. Mosquito ShieldTM is a passive, transfluthrin-based emanator designed to provide month-long protection in enclosed or semi-enclosed spaces. This study evaluated its entomological efficacy under experi...

BackgroundReliable identification of early predictors of adverse outcomes was essential during the pre-vaccination phase of the COVID-19 pandemic. Few studies have comprehensively integrated clinical presentation, laboratory parameters including arterial blood gas analysis, and chest computed tomography (CT) findings within a single well-characterized cohort, particularly in underrepresented regions of Brazil. MethodsThis retrospective cohort study included 482 consecutive adults (median age 61...

ObjectiveThis study explored the recovery experiences of individuals who report having (largely) recovered from long covid and who attributed their improvement to mind-body approaches. Design, setting and participantsWe conducted an explorative qualitative study using purposive recruitment through social media and snowball sampling. Eighteen adult women (aged 37-62 years), who self-identified as having had long covid and having substantially recovered through mind-body approaches participated i...

Microbial keratitis is a sight-threatening corneal infection with varying etiological agents, primarily bacteria and fungi. Assessing and contrasting the virulence factors of microorganisms isolated from a non-contact lens-associated keratitis (NCLAK) and contact lens-associated keratitis (CLAK) is the goal of the current investigation. Samples were collected from over 60 patients and analysed using standard microbiological techniques, including culture, Gram staining, KOH mount, biochemical tes...

BackgroundImproving tuberculosis (TB) treatment success is critical for improving the health of individuals with TB, reducing transmission, and lowering treatment costs. We conducted a four-arm randomized controlled trial (RCT) to evaluate whether three digital interventions with increasing support improved treatment outcomes compared to the standard of care. MethodsIn this open-label, parallel RCT in Kenya, all TB patients at 902 participating clinics who had at least 2 months of treatment rem...

BackgroundCambodia has made great progress in reducing malaria transmission and is targeting elimination. While this progress is particularly marked for Plasmodium falciparum, the situation is different for Plasmodium vivax. It is generally assumed that symptomatic patients are effectively diagnosed using rapid diagnostic tests (RDTs), regardless of transmission intensity. MethodsIn 2023 we conducted a cross-sectional survey among 986 treatment-seeking patients in 6 provinces of Cambodia with v...

BackgroundThe widespread insecticide resistance increasingly threatens malaria elimination, prompting a reassessment of vector control strategies. As Tanzania transitions from standard pyrethroid-only insecticide-treated nets (ITNs) to new-generation nets, evaluating the impact of this shift on malaria transmission and resistance is critical. MethodsUsing the agent-based malaria model, EMOD, we assessed the impact of three ITN types, standard pyrethroid-only nets, pyrethroid-PBO nets (Olyset(R)...

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSINTRODUCTIONC_ST_ABSTreatment response in Alzheimers disease (AD) varies substantially across patients, yet no validated frameworks exist to estimate heterogeneous treatment effects (HTE) from observational data while controlling for confounding bias. METHODSWe developed a causal machine learning framework integrating expert-guided causal graphs, complementary HTE estimators, sensitivity analyses, and policy learning. We applied it to cholinesterase inhibitors (C...

BackgroundThe 2024 blood culture bottle shortage brought diagnostic resource allocation to the forefront, reflecting persistent, foundational challenges with low-value testing and empiric treatment approaches under clinical uncertainty. ObjectiveTo determine whether a machine learning approach using electronic medical record data can predict bacteremia more effectively than existing systems and practices to guide diagnostic testing and empiric treatment strategies. MethodsIn a retrospective co...