Wildfire events pose increasing threats to public health, especially concerning the respiratory system. The chemistries of emission mixtures vary widely based on factors including fuel source, burn temperature, and atmospheric and photochemical processes. Because of these varying exposure conditions, differing biological responses may occur, making it difficult to identify common mediators of wildfire smoke-induced disease with which to base health and risk assessments upon. To address this difficulty, this study set out to identify genes and modes of action highly shared across biological responses to wildfire-relevant exposures and respiratory disease outcomes. Specifically, we mined the Molecular Signatures Database and Computational Toxicogenomics Database for human consensus gene expression signatures of respiratory diseases and infections putatively linked to wildfire smoke exposures. These gene signatures were then compared to transcriptomic signatures measured in the lung of mice exposed to condensates derived from variable controlled biomass burn conditions. Data cleaning followed by similarity scoring, clustering, data reduction, and pathway enrichment methods were used to identify patterns amongst exposure and disease profiles. Fifty-three genes were identified as highly shared across signatures of both exposure and disease. Jaccard-based similarity scoring analyses of these top shared genes revealed asthma as the respiratory disease most similar across the majority of biomass conditions under evaluation. Pathway enrichment of these top shared genes identified interleukin signaling, oxidative stress response, and estrogen signaling as mechanisms of action likely linking exposure-to-disease outcomes across these variable smoke exposure conditions. Altogether, these results highlight consistent mediators to use in future health risk-based evaluations of wildfire smoke emissions.
There are various radiopharmaceuticals and hybrid imaging techniques for evaluating pediatric patients in the acute care setting. The focus of this article is on common nuclear medicine applications in pediatric acute care. Brain scintigraphy is an important ancillary test for evaluation of brain death/death by neurologic criteria when the clinical examination or apnea test cannot be safely or completely performed. Ventilation-perfusion scintigraphy is considered as a safe and useful test for suspected pulmonary embolism in hemodynamically stable children, especially when the chest radiograph is normal or near normal and radiation reduction is important. 99mTc-pertechnetate scintigraphy is stated to be the best noninvasive nuclear medicine test for detecting ectopic gastric mucosa in Meckel's diverticulum, whereas 99mTc-labeled red blood cell scintigraphy is useful for evaluating active or intermittent lower gastrointestinal bleeding from different causes. Hepatobiliary scintigraphy provides functional assessment of biliary excretion and is useful for evaluation of acute cholecystitis, choledochal cysts, and bile leaks. 99mTc-DMSA renal cortical scintigraphy is a sensitive method for detecting acute pyelonephritis and renal cortical scarring, while 99mTc-MAG3 renal scintigraphy is used to evaluate early and late complications of renal transplantation. Bone scintigraphy is considered as a valuable imaging modality for evaluation of osteomyelitis, occult fracture, stress injury, sickle cell related bone pain, and selected cases of suspected physical abuse, especially when whole body assessment is needed. 18F-FDG PET/CT has an increasing role in selected children with fever of unknown origin and inflammatory disorders. Moving forward, continued refinement of pediatric administered activities, wider use of SPECT/CT and PET-based imaging and updated pediatric-specific guidelines are expected to further improve the role of nuclear medicine in acute pediatric care.
The emergence of methicillin-resistant Staphylococcus aureus (MRSA) calls for novel antibiotic adjuvants. Carvacrol (Car), a natural monoterpene phenol derived from the essential oils of aromatic plants, exhibits membrane-active properties and has potential as an antibacterial adjuvant. Here, we found that Car markedly enhanced the bactericidal activities of Gentamicin (Gen) against MRSA. Mechanistically, Car dissipated membrane potential, inhibited respiratory chain dehydrogenase activity, and depleted intracellular ATP. Moreover, Car promoted membrane lipid peroxidation, ultimately leading to structural and functional membrane damage and bacterial death. Notably, pharmacological perturbation of respiratory and metabolic pathways further supported that this synergistic effect depends on bacterial respiratory bioenergetics. In addition, the combination showed favorable in vivo antibacterial efficacy in both Galleria mellonella and murine infection models, without apparent toxicity under the tested conditions. Collectively, these findings indicate that Car may serve as a natural antibacterial adjuvant for combination therapy against drug-resistant infections.
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Bubble humidification is often utilized with low-flow nasal cannulas despite a lack of evidence to support its use. The practice was discontinued in our children's hospital based on recommendations from the American Association for Respiratory Care clinical practice guideline for management of pediatric patients with oxygen in the acute care setting and other available literature. The aim of this study was to evaluate staff feedback post de-implementation of the practice. Following staff and stakeholder communication, bubble humidification for low-flow oxygen therapy was discontinued in May 2024. Respiratory and nursing staff were invited to complete a post-de-implementation survey in August 2024. Domains included respondent demographics, clinical practice guideline familiarity, receipt of communication, agreement with the practice change, and patient concerns. Responses were collected electronically. Responses from 132 staff were analyzed. The majority were female (105, 79%), nurses (81, 61%), and had 5 years or less of work experience (49, 37%). Eighty-six (65%) reported familiarity with the guideline. Overall, 59 (45%) were indifferent to the practice change and 46 (35%) disagreed. More than half (75, 57%) were concerned about patients. Nurses were significantly younger (≤25 years, P = .052; 26-34 years, P = .005) and less experienced (0-5 years, P = .009) than respiratory therapists. There were no significant differences between disciplines for patient concern. Nasal irritation/dryness was the most common theme for the reason for disagreement and patient concern followed by epistaxis. Few nurses and respiratory therapists agreed with discontinuing bubble humidification despite clinical practice guideline recommendations, and many were concerned about patients. Prospective, randomized clinical trials for acute and chronic oxygen delivery are warranted.
The COVID-19 disease, presenting with complex immune dysregulation and leading to life-threatening organ dysfunction, represents a paradigm of viral sepsis. As heterogeneity of clinical presentation is contained in COVID-19 (one pathogen, one source of infection) related to bacterial sepsis, and due to the urgency of the pandemic for immediate responsive research networks, many trials have been conducted providing beneficial patient outcomes and changing the natural course of disease. In this review, we summarize lessons learnt from the COVID-19 pandemic related to immunotherapy, management of acute respiratory failure (ARF) and post-infectious sequalae that could be implemented in sepsis care. Biomarker-guided immunotherapy in a tailored, precision medicine approach may alter sepsis outcomes. Measures used during the pandemic to handle with ARF such as high flow nasal oxygen and awake prone position have been already incorporated in standard-of-care sepsis management. Last, post-infectious sequalae present equally after sepsis (post-sepsis syndrome-PSS) and COVID-19 (post-covid syndrome-PCS); management of PSS may share details from PCS management and vice versa. Teachings from the pandemic are not limited to the above. Overall, the COVID-19 pandemic has transformed global health to a top priority; focus should remain now active on the sepsis agenda.
Human metapneumovirus (hMPV) is a major cause of pediatric acute lower respiratory tract infections (ALRTIs), yet vaccine development has been hindered by the intrinsic metastability of the prefusion F glycoprotein (pre-F). Here, we used a structure-based design strategy to stabilize hMPV pre-F while preserving neutralization-sensitive epitopes. By applying combined stabilizing elements, including disulfide bonds, a designed salt bridge, and a trimer-interface sequence swap, we generated VM-874, a pre-F-stabilized trimer that was expressed at high levels in 293F cells and exhibited improved thermal stability and stress-resistant antigenicity. VM-874 also retained binding to multiple conformation-sensitive monoclonal antibodies following thermal and storage stress. VM-874 elicited high serum neutralizing titers against both hMPV A2 and B1 strains and conferred protection in BALB/c mice and cotton rats, as evidenced by reduced pulmonary viral burden and attenuated lung pathology after challenge. Although VM-874 elicited antibodies that cross-bound respiratory syncytial virus (RSV) F protein, no RSV-neutralizing activity was detected, underscoring the need to distinguish cross-reactivity from heterologous protection in combined RSV/hMPV vaccine strategies.
Neutrophilic inflammation is a common feature of chronic obstructive pulmonary disease (COPD). Mitiperstat, an inhibitor of myeloperoxidase expressed in neutrophils, may have potential as a COPD treatment. This phase 2a, randomised, placebo-controlled, double-blind, parallel-arm, event-driven trial evaluated the efficacy and safety of mitiperstat 5 mg daily up to 24 weeks (NCT05492877). Adults (40-80 years) with moderate-to-severe COPD, at high risk of exacerbation, and receiving dual or triple inhaled therapy were included. The primary endpoint was time to first composite endpoint for exacerbations in COPD (COPDCompEx) event. Secondary endpoints included time to first moderate-to-severe COPD exacerbation, post-bronchodilator forced expiratory volume in 1 s (post-BD FEV1) change at Week 12, respiratory symptoms, disease impact and safety. Overall, 381 participants (mean age, 66.0 years; 39.6% female) were randomised to mitiperstat (n=189) or placebo (n=192). In total, 125 (66.1%) mitiperstat-treated versus 125 (65.1%) placebo-treated participants experienced COPDCompEx events over 24 weeks. There was no improvement in time to first COPDCompEx event (hazard ratio [HR] 1.07 [90% confidence interval (CI) 0.87, 1.32]; p=0.599) or time to first moderate-to-severe COPD exacerbation (HR 1.23 [90% CI 0.88, 1.73]) with mitiperstat versus placebo. Improvements in post-BD FEV1, respiratory symptoms or disease impact were not seen with mitiperstat. A similar proportion of participants in both groups reported adverse events; seven mitiperstat-treated participants and two placebo-treated participants had pneumonia during the study. These results indicate that the risks outweigh the benefits of mitiperstat as a treatment for COPD.
Pulmonary function tests (PFTs) are central to assessing ventilatory impairment but are often limited by accessibility, repeatability, and patient compliance, particularly in community and longitudinal monitoring settings. This study investigates
whether acoustic features of voluntary coughs can serve as low burden surrogate signals reflecting trends in spirometry related indices of ventilatory impairment. We propose a dual output ensemble learning framework that integrates deterministic regression and probabilistic interval estimation to jointly model spirometry related parameters from cough acoustics and basic demographic information. Fifty eight cough derived acoustic features and four biometric variables were analysed using an optimized Extreme Gradient Boosting (XGBoost) model for point estimation, coupled with Natural Gradient Boosting (NGBoost) for uncertainty quantification. A hybrid Bayesian-Whale Optimization strategy was employed for robust hyperparameter tuning. In a cohort of 278 subjects with heterogeneous respiratory conditions, the proposed framework achieved root mean square errors of 0.20 L for forced vital capacity (FVC) and 0.27 L for forced expiratory volume in one second (FEV1), with coefficients of determination up to 0.94 and 0.87, respectively. Interval estimates provided uncertainty bounds consistent with model reliability, with the actual prediction interval coverage probabilities reaching 84.0% for FVC and 77.8% for FEV1. Performance for the composite FEV1/FVC ratio was comparatively lower, reflecting the increased variability of ratio based metrics. These findings suggest that cough acoustics encode physiologically relevant
information associated with ventilatory impairment and can support proxy trend modelling of spirometry related indices, rather than direct spirometry replacement. The proposed framework demonstrates the feasibility of cough based physiological assessment
for low cost respiratory screening and longitudinal monitoring, particularly where conventional spirometry is impractical. Larger multi centre studies are warranted to further evaluate generalizability and clinical integration.
In 2024, two respiratory syncytial virus (RSV) immunisation strategies were introduced on the island of Ireland: nirsevimab in Republic of Ireland (ROI) and RSVpreF in Northern Ireland (NI). The primary objective was to estimate effectiveness against hospitalised RSV-associated acute lower respiratory infection (ALRI) in infants <6 months. The secondary objective was to compare impact on emergency department (ED) bronchiolitis attendances. We conducted a multicentre, test-negative, case-control study across five sites during the 2024/25 season. Effectiveness against hospitalisation was estimated using multivariable logistic regression adjusting for age <3 months, sex, and prematurity. Infants born after 1 September 2024, hospitalised with ALRI, and tested for RSV were eligible. Time series modelling compared ED bronchiolitis attendances during the study season with five preceding seasons. 254 infants were included (ROI:165, NI: 89). In ROI, 34% of cases and 83% of controls received nirsevimab; in NI, 6% and 30% received RSVpreF respectively. Adjusted effectiveness against hospitalisation was 90.7% (95% CI 80.7-95.8) for nirsevimab and 83.9% (95% CI 41.5-96.6) for RSVpreF. Modelling showed significant reductions in ED bronchiolitis attendances; greater in ROI (52%) than NI (37%). Both interventions were highly effective against RSV-ALRI hospitalisation. However, coverage differed markedly, with important implications for population-level impact.
Mild and moderate asthma are the most common forms of asthma, but they often remain poorly controlled due to inappropriate treatment strategies and low adherence. Formal consensus on best practices for managing mild-to-moderate asthma is still lacking. To achieve formal consensus on the management of mild-to-moderate asthma and validate the appropriateness and clinical feasibility of the recommendations in clinical practice. A modified Delphi process involving a panel of respiratory experts was employed to formulate consensus statements across the following key domains identified through a cross-sectional survey administered to Italian allergists and immunologists: definition of asthma control, tools for assessment of asthma control, patient phenotyping, personalized treatment, and patient education and empowerment. The appropriateness and clinical feasibility of the agreed statements were validated with a RAND/UCLA method. Full consensus was reached on asthma control in mild-to-moderate asthma, defined as the absence of symptoms, exacerbations, limitation of daily activities, and oral corticosteroids, and the optimization of lung function. Assessment of control, future risk, and phenotype should be performed with appropriate tools and timing, to implement proactive management especially in patients at risk of exacerbations and disease progression. This study provides a comprehensive, expert-driven consensus for the management of mild-to-moderate asthma, formally validated for appropriateness despite variability in real-world implementation. The findings support a patient-centric, proactive approach and offer practical recommendations to bridge the gap between guidelines and clinical practice.
The opioid epidemic remains a persistent public health challenge in the United States, leaving many people affected by or vulnerable to opioid use disorder (OUD). Although US Food and Drug Administration-approved medications for OUD improve the odds of recovery and reduce mortality, relapse rates remain high and access, adherence, and individual response variabilities limit their overall impact. The ongoing burden of OUD therefore underscores the need to develop additional therapeutics that target complementary biological mechanisms and support long-term recovery. One strategy of interest is to delineate the biological overlap between OUD and other motivated behaviors, particularly the neurobiology underlying appetitive and reward-driven processes. The orexigenic peptide hormone ghrelin, often referred to as the "hunger hormone," regulates energy homeostasis, hedonic feeding, and reward sensitivity by binding to the growth hormone secretagogue receptor 1α (GHS1αR), a receptor expressed in mesolimbic circuits implicated in addiction. In the present study, we used the inverse agonist/antagonist PF5190457 to assess the impact of full GHS1αR blockade on fentanyl-mediated behaviors in preclinical models. We found that PF5190457 significantly reduced fentanyl self-administration and attenuated drug-seeking during cue tests while maintaining a favorable pharmacological and safety profile in risk assessment assays, including measures of withdrawal and respiratory depression. Collectively, these findings demonstrate a functional role for ghrelin-GHS1αR signaling in the reinforcing effects of fentanyl and positions GHS1αR inverse agonism as a promising, mechanistically novel therapeutic strategy for OUD treatment. SIGNIFICANCE STATEMENT: The present work demonstrates that the growth hormone secretagogue receptor 1α (GHS1αR) inverse agonist/antagonist PF5190457 reduces fentanyl self-administration and drug-seeking while maintaining a favorable safety profile in male rats, supporting ghrelin-GHS1αR modulation as a promising therapeutic strategy for opioid use disorder.
Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), remain major challenges in critical care medicine, characterized by alveolar-capillary barrier disruption, excessive inflammation, and impaired gas exchange. With the growing aging population, aging has emerged as an important determinant of ALI/ARDS susceptibility, progression, and prognosis. Aging promotes pulmonary vulnerability through multiple interconnected mechanisms, including immune dysregulation, chronic inflammation, cellular senescence, mitochondrial dysfunction, and impaired tissue repair capacity, thereby facilitating inflammatory imbalance and defective lung regeneration. This review summarizes the key mechanisms underlying aging-associated susceptibility to ALI and discusses emerging therapeutic strategies targeting aging-related alterations, with emphasis on their translational challenges and clinical implications. These insights may provide new perspectives for the development of precision prevention and treatment approaches for elderly patients with ALI/ARDS.
Physical conditions are increasingly recognized as contributors to suicide risk, independent of psychiatric comorbidity. The aim of this study was to descriptively examine the association between a range of lifetime physical conditions and suicide attempts in a large, population-based US sample. Data were analyzed from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III; N = 36,171). Lifetime suicide attempts (n = 1995) were assessed via self-report. Physical conditions were self-reported based on physician diagnosis and included a range of metabolic, infectious, cardiovascular, gastrointestinal, neurological, respiratory, and autoimmune diseases. Over 20% of those with arteriosclerosis and hypertension, arthritis, and dyslipidemia, sleep problems, and cardiovascular disease (20.1-27.9%) endorsed a lifetime suicide attempt. With the exception of cancer, all physical conditions were associated with suicide attempts. After adjustment for sociodemographic factors and psychiatric conditions, most associations were attenuated but remained significant (adjusted odds ratio [AOR] range across the significant conditions: 1.16-2.75), with the strongest associations observed for epilepsy and HIV/STIs. Only cancer, osteoporosis, and traumatic brain injury were not significantly associated with suicide attempts in the fully adjusted models. Increasing number of health conditions was also significantly associated with suicide attempts across all models. Findings may inform suicide prevention efforts by highlighting the need for integrated physical and mental health care, particularly for patients living with multimorbidity. Results were correlational and future research should examine relationships longitudinally.
Tezepelumab has demonstrated efficacy in patients with severe, uncontrolled asthma in randomized controlled trials (RCTs). Real-world studies assessing patient-reported outcomes are required to complement RCT findings. ASCENT is an ongoing, multi-country, single-arm, prospective, real-world study assessing asthma symptom control in participants (≥12 years old) with severe, uncontrolled asthma initiating tezepelumab as routine standard of care in Europe and Canada. This interim analysis assessed changes from baseline in Asthma Control Questionnaire-6 (ACQ-6) score, St George's Respiratory Questionnaire (SGRQ) total score, and pre-bronchodilator forced expiratory volume in 1 second (FEV1) at weeks 4, 12, and 24, and the annualized asthma exacerbation rate (AAER) in the 52-week baseline and 24-week follow-up periods. Overall, 211 participants were included in this analysis. ACQ-6 and SGRQ total scores improved from baseline to week 4 (least-squares mean [95% CI] change: -0.99 [-1.13, -0.84] and -13.2 [-15.6, -10.8], respectively) and further improved to week 24 (-1.28 [-1.44, -1.12] and -19.8 [-22.6, -17.0], respectively). AAER decreased by 65% (95% CI: 55, 73) between baseline (1.75) and follow-up (0.61) periods. Least-squares mean changes from baseline in pre-bronchodilator FEV1 at weeks 4 and 24 were 0.09 L (0.03, 0.14) and 0.12 L (0.06, 0.18), respectively. These changes were observed across asthma phenotypes and biomarker levels. Patients with severe, uncontrolled asthma treated with tezepelumab had clinically meaningful improvements in asthma control, health-related quality of life, lung function, and exacerbations as early as week 4 through to week 24, irrespective of asthma phenotype. NCT05677139.
Pseudomonas aeruginosa infection remains a major challenge in donor lung management and post-transplant respiratory care, particularly in the setting of antimicrobial resistance. Ex vivo lung perfusion (EVLP) provides an opportunity for localized antimicrobial intervention before transplantation and allows detailed assessment of infection-associated lung injury under controlled conditions. In this study, we evaluated inhaled sphingosine in a porcine EVLP model of acute P. aeruginosa airway contamination using three experimental groups: uninfected controls, infected lungs treated with 0.9% NaCl, and infected lungs treated with sphingosine. This design allowed us to assess both the impact of P. aeruginosa infection on EVLP physiology and the effects of sphingosine on bacterial burden and infection-associated lung changes. Infected porcine lungs showed greater declines in dynamic and static compliance than uninfected controls, whereas pulmonary artery pressure, peak airway pressure, oxygen-exchange capacity, lactate accumulation, lung weight gain, and histological injury scores were not significantly worsened under the present experimental conditions. Inhaled sphingosine reduced bronchial P. aeruginosa CFU counts, whereas 0.9% NaCl did not. Sphingosine treatment did not further impair lung physiology, oxygenation, lactate accumulation, histological injury, or lung weight gain. Mechanistic analyses showed association of sphingosine with bacterial cardiolipin and increased colocalization of sphingosine with P. aeruginosa, consistent with a membrane-associated antibacterial mechanism described in previous studies. In exploratory experiments using four explanted human recipient lungs, sphingosine inhalation increased sphingosine levels in bronchial and parenchymal tissue and altered related sphingolipid metabolites, including sphingosine-1-phosphate, ceramide, and sphingomyelin, without apparent acute histological damage in assessed airway samples. One of the four human specimens showed bacterial colonization, in which a marked reduction in detectable bacterial growth after sphingosine inhalation was observed as a hypothesis-generating finding. Together, these data suggest that inhaled sphingosine can reduce acutely accessible bronchial P. aeruginosa burden during porcine EVLP without detectable short-term adverse effects and provide a basis for further investigation of sphingosine-related lipid metabolism and local antimicrobial strategies during EVLP.
Influenza A and B viruses are considerable public health threats. Annual seasonal epidemics are driven by antigenic drift and cause an estimated 3-5 million severe cases and 290,000-650,000 deaths annually. The clinical presentation of seasonal influenza is typically an abrupt, uncomplicated acute respiratory illness with full recovery; however, it can lead to severe, life-threatening complications in individuals at high risk. Antigenic shift caused by reassortment of a seasonal influenza A virus with avian and/or swine influenza A viruses has led to unpredictable pandemics. The successful cross-species transmission of influenza A viruses requires key viral adaptations, including changes in receptor specificity and compatibility with host factors such as ANP32A. Host defence involves a layered innate response, which is antagonized by proteins, such as non-structural protein 1, and a robust adaptive immunity comprising cytotoxic CD8+ T cells targeting conserved internal proteins and B cells producing neutralizing antibodies. Diagnosis primarily depends on highly sensitive PCR-based methods and multiplexed rapid antigen tests. Prevention involves annually updated seasonal vaccines (including inactivated, live attenuated and protein-based vaccines), while treatment relies on early use of neuraminidase and polymerase acidic protein inhibitors. Research priorities include the development of improved vaccines and a better understanding of influenza virus transmission from animals to humans.
In this study, we demonstrate for the first time that post-injury creatine supplementation (300mg/kg, p.o.) administered for two weeks attenuates blood-brain barrier disruption, cortical lesion volume (by ~60%), spatial memory deficits (reducing escape latency by ~50% in the Barnes maze), hippocampal theta/delta rhythm alterations, and epileptiform activity in 35-day-old male rats subjected to severe fluid percussion injury (FPI). In the hippocampus, the FPI protocol did not cause overt neuronal loss-particularly of parvalbumin-positive neurons in the CA1 and CA2 regions-but it significantly reduced creatine levels and induced marked mitochondrial dysfunction. These alterations were evidenced by impaired MTT reduction, disrupted mitochondrial membrane potential (Δψ), decreased SDH activity, inhibition of respiratory chain complexes I-III, COX, citrate synthase (CS), and CKm activity, together with increased mitochondrial oxidative stress (enhanced DCFH-DA oxidation, elevated 4-hydroxynonenal levels, depletion of free -SH groups, and reduced GSH levels). We propose a mechanistic cascade wherein mitochondrial dysfunction and elevated oxidative stress drive the inhibition of Na⁺,K⁺-ATPase, which in turn contributes to neuronal hyperexcitability and cognitive deficits. Creatine's ability to maintain mitochondrial integrity directly interrupts this cascade, protecting against dysfunctions in these essential ion-gradient systems. In conclusion, post-injury creatine supplementation preserves mitochondrial function, maintains Na⁺,K⁺-ATPase activity, and prevents epileptiform activity and cognitive deficits, highlighting creatine as a promising strategy to mitigate secondary injury. However, these findings must be interpreted in light of certain limitations, including the use of a male-only cohort, a single time-point assessment, and the correlational nature of the proposed mechanistic pathways, warranting further investigation.
In the current study, a novel formulation comprising gold Nanoparticles (AuNPs) and Fagonia arabica L. (F. arabica L.) phytochemicals, was designed and conjugated to evaluate inhibitory potential against Mycobacterium tuberculosis (Mtb). The chemically synthesized AuNPs were characterized followed by anti-Mtb potential of F. arabica L. extracts were which is significantly increased when used as a conjugate with AuNPs. The drug-resistant Mtb isolates in MGIT show that F. arabica L. phytochemicals, in conjugation with AuNPs, exhibit greater inhibitory activity than plant extracts alone at a concentration of 4.28 µg/mL. In vivo analysis showed no significant toxicity of the nanoconjugates. The plant extract was analyzed using ultra-high performance liquid chromatography in which 17 antimycobacterial components, including 14 from Traditional Chinese Medicine Class, were also identified. While plant-mediated AuNPs synthesis and their general antibacterial properties have been reported, our study offers distinct novelty through the specific use of F. arabica L., direct comparison of chemical versus green synthesis, the efficacy against MDR clinical isolates, and combined in vitro efficacy and in vivo safety validation. Overall, a good anti-TB activity of F. arabica L. in conjugation with AuNPs was found, paving the way for the development of new anti-TB agents against drug-resistant Mtb.