Search Results (75)

Background/Objectives: Reactive oxygen species (ROS) are key effectors of innate immunity but can also contribute to inflammation and tissue injury when their production is dysregulated. Although antibiotics are primarily selected for their antimicrobial activity, prolonged treatment may also influence host immune responses. However, the effects of anti-tuberculosis drugs on ROS production across innate immune cell subsets have not been assessed, especially not for novel drugs currently used against multi drug-resistant (MDR) tuberculosis (TB). Methods: Whole blood from healthy donors was incubated with seven antimycobacterial drugs used against MDR TB at sub-therapeutic, therapeutic, and supra-therapeutic concentrations. ROS production was quantified by flow cytometry using dihydrorhodamine 123 (DHR-123) in neutrophils, classical monocytes, and eosinophils under unstimulated conditions or following stimulation with Escherichia coli, fMLP, or PMA. Results: Bedaquiline and clofazimine decreased ROS production in neutrophils and classical monocytes across multiple stimuli (median values of Rh-123⁺ classical monocytes after E. coli stimulation without BDQ was 30.8% versus 24.9% with 1 µg/mL BDQ (p < 0.05, therapeutic concentration) and 31.3% without CFZ versus 19.2% with 1 µg/mL CFZ (p < 0.01, therapeutic concentration) in the same conditions). In contrast, levofloxacin and linezolid showed no detectable impact on ROS production in any cell population. Pretomanid uniquely induced a reduction in ROS generation in eosinophils and classical monocytes while sparing neutrophil oxidative burst activity, distinguishing it from other antibiotics tested (34.1% decrease in Rh-123 MFI of eosinophils between the control and PA 3 µg/mL after fMLP stimulation, p < 0.01, therapeutic concentration). Conclusions: These findings demonstrate that first line drugs against MDR TB display heterogeneous and cell type-specific effects on innate immune oxidative responses. Such differential effects on host immunity may have implications for both antimicrobial efficacy and inflammation control during tuberculosis treatment. Full article

Tuberculosis (TB) treatment is severely hampered by the rise in multi-drug-resistant strains and the prevalence of drug-induced toxicities. Host-Directed Therapies (HDTs) have emerged as a promising strategy to overcome these challenges by modulating innate immunity and circumventing Mycobacterium tuberculosis (Mtb) evasion mechanisms. A hallmark of Mtb pathogenesis is the arrest of phagosome maturation and the induction of host cell necrosis over protective apoptosis. In this study, we investigated the potential HDT effects of α-Lipoic acid (α-LA), a well-known antioxidant and metabolic cofactor, within an in vitro model of Mtb-infected THP-1 macrophages. Our findings indicate that α-LA treatment modulates the macrophage redox state and selectively promotes apoptosis in infected cells without increasing necrotic lysis. Furthermore, α-LA administration led to a significant, dose-dependent restoration of phagolysosome acidification, effectively reversing the maturation blockade imposed by Mtb. Notably, this enhanced acidification inversely correlated with intracellular bacterial survival. These results suggest that α-LA might act as a multifaceted HDT agent capable of restoring both host-protective cell death and phagosomal microbicidal mechanisms. Given its established safety profile and its ability to complement standard anti-TB drugs like Bedaquiline (BDQ), α-LA represents a highly promising candidate for adjunct therapy to improve TB treatment outcomes and mitigate the impact of antibiotic resistance. Full article

Tuberculosis is one of the hardest-to-treat bacterial diseases with a high capacity to develop antibiotic resistance. The treatment scheme based on bedaquiline and linezolid was introduced in Russia in 2014 and, since 2018, has been widely used for the treatment of resistant tuberculosis. In our study of clinical M. tuberculosis isolates, we identified a case of a recent transmission of a strain with mutations in the genes rv0678 and rplC, associated with resistance to bedaquiline and linezolid. We analyzed five isolates obtained from patient A between 2015 and 2019 after unsuccessful treatment and three isolates from patient B obtained between diagnosis in 2019 and death in mid-2020 via whole-genome sequencing and 24-loci MIRU-VNTR genotyping. During the treatment of patient A, a large spectrum of different mutations in rv0678 developed, accompanied by an increase in bedaquiline MIC from 0.06 to 0.5 mg/L. Simultaneously, rplC C154R substitution emerged, leading to linezolid resistance. The isolates from patient B contained nearly the same mutation spectra as the isolates from patient A, differing in only four variants that emerged during transmission. The possible transmission event must have occurred in a public place in Moscow, since there was no evidence of direct contact between the patients. This finding confirms the worrying trend of untreatable M. tuberculosis strains circulating in the general population. Full article

Background: South Korea continues to report a considerable burden of drug-resistant tuberculosis (TB). Bedaquiline-containing regimens are recommended for multidrug-resistant pulmonary TB, but evidence regarding the optimal treatment for extrapulmonary manifestations such as spinal TB remains limited. Case presentation: Herein, we report two cases of drug-resistant tuberculous spondylitis that were successfully managed using bedaquiline-containing regimens. Case 1 involved a 67-year-old man who was receiving chemotherapy for lymphoma and had a history of spinal TB treated 20 years earlier. The patient presented with dysphagia and upper limb weakness. Cervical magnetic resonance imaging revealed C4–5 spondylitis with an epidural abscess. He underwent surgical treatment, and Mycobacterium tuberculosis resistant to rifampin was isolated from cultured intraoperatively obtained tissue specimens. The patient received an antibiotic regimen consisting of bedaquiline, levofloxacin, linezolid, cycloserine, and clofazimine. Clinical and radiological improvements were achieved after 12 months of this treatment; bedaquiline was included in the regimen for the first 6 months, while the other agents were continued for the entire course. Case 2 involved a 71-year-old man with T12–L2 spondylitis and a left psoas abscess. Tissue culture confirmed Mycobacterium tuberculosis resistant to isoniazid, rifampin, and ethambutol. The patient was started on the same bedaquiline-containing regimen. Clinical and radiological improvements were observed after 18 months of this therapy, including 6 months of bedaquiline. Conclusions: Our clinical experiences suggest that bedaquiline-containing regimens represent a feasible and effective therapeutic option for drug-resistant tuberculous spondylitis. Larger studies are warranted to establish the optimal management strategies for extrapulmonary drug-resistant TB infections. Full article

Tuberculosis (TB) remains a critical global public health challenge, requiring therapeutic strategies that ensure high cure rates while minimizing bacillary transmission. The 2022 World Health Organization (WHO) update for drug-resistant TB treatment prioritized a novel, 6-month, all-oral regimen composed of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) as the preferred treatment for rifampicin- and multidrug-resistant tuberculosis (RR-/MDR-TB). However, the clinical success of this shortened therapy is intrinsically linked to managing complex drug–drug interactions and treatment-emergent adverse effects which may necessitate regimen modifications. This article provides a comprehensive pharmacological review of the BPaLM components, detailing their mechanisms of action, pharmacokinetics (absorption, metabolism, and excretion), and safety profiles. Furthermore, we analyze critical drug interactions—including those involving food and antacids—and provide evidence-based guidance for special clinical populations, such as pregnant and breastfeeding women, and patients with hepatic or renal impairment. Mastery of these pharmacological nuances is essential for clinicians to optimize treatment adherence and ensure improved treatment completion rates and reduced resistance emergence. Full article

Background: Drug-resistant tuberculosis (DR-TB) continues to pose a major challenge in Limpopo Province, a predominantly rural region of South Africa with high prevalence of HIV and mobility of the cross-border population. Despite the scale-up of short all-oral bedaquiline-based regimens, there is limited recent provincial evidence describing DR-TB epidemiological characteristics and treatment outcomes in the post-COVID-19 period. This study aimed to assess resistance patterns, treatment outcomes, and factors associated with unfavorable outcomes among patients with DR-TB in Limpopo Province from 2020 to 2024. Methods: A retrospective cohort study was conducted using routinely collected data from the Electronic Drug Resistant Tuberculosis Register (EDRWeb). All laboratory-confirmed DR-TB cases diagnosed between January 2020 and December 2024 were included. Descriptive statistics were used to summarize demographic and clinical characteristics. Multivariable logistic regression was performed to identify predictors of unfavorable outcomes (treatment failure, death, and loss to follow-up). Kaplan–Meier survival analysis was used to estimate survival probability following treatment initiation. Results: A total of 1240 DR-TB cases were recorded, of which 1165 (94%) had documented treatment outcomes. Rifampicin-resistant TB (RR-TB) predominated throughout the study period, accounting for 76% (951/1240) of cases and remaining stable over time. Treatment success improved from 173/260 (67%) in 2020 to 130/166 (78%) in 2024, while loss to follow-up declined from 34/260 (13%) to 4/166 (2%). Kaplan–Meier survival analysis showed that mortality occurred predominantly during the early phase of treatment. Patients receiving bedaquiline-containing regimens demonstrated significantly higher survival probability compared with those not receiving bedaquiline (log-rank p = 0.024; HR 0.58, 95% CI: 0.35–0.94). In multivariable analysis, HIV infection was independently associated with unfavorable outcomes (aOR 1.36; 95% CI: 1.04–1.77; p = 0.025), while increasing age showed a modest association with poorer outcomes. Conclusions: Treatment outcomes for DR-TB improved over the study period, accompanied by declining loss to follow-up and improved survival. The survival advantage observed among patients receiving bedaquiline-containing regimens supports continued prioritization of bedaquiline-based treatment strategies in DR-TB management. Strengthening access to these regimens, alongside integrated HIV care, may further improve treatment outcomes in Limpopo Province and similar high-burden settings in South Africa. Full article

Background: Bedaquiline (BDQ) resistance poses a serious threat to its long-term efficacy, particularly in high-burden settings like South Africa, where data remain scattered and largely non-synthesized. Objective: This study aimed to estimate the trends of BDQ resistance in drug resistant tuberculosis (DR-TB), characterize associated resistance mechanisms, and evaluate implications for treatment outcomes in South Africa. Eligibility criteria: We included primary studies reporting BDQ resistance, resistance mechanisms, minimum inhibitory concentrations (MICs), or treatment outcomes among patients with MDR- or XDR-TB treated with BDQ-containing regimens in South Africa. Information sources: PubMed, Web of Science, and Embase were searched for studies published between January 2016 and July 2024. Risk of bias: Study quality was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Synthesis of results: Random-effects meta-analysis with Freeman–Tukey double-arcsine transformation was used to estimate pooled BDQ resistance prevalence. Heterogeneity, sensitivity analyses, and publication bias were assessed. Results: Twenty-eight studies were included. The pooled prevalence of BDQ resistance was 6.0% (95% CI: 4.1–7.9%; I² = 62%). Treatment success averaged 63.5%, and culture conversion reached 84.1%. Resistance-associated mutations were most frequently reported in Rv0678, followed by atpE and pepQ, often associated with elevated MICs (≥2–4 μg/mL). Evidence of small-study effects was observed (Egger’s test, p = 0.0012). A pooled prevalence estimate was calculated; however, evidence of small-study effects suggests that estimates should be interpreted cautiously. Limitations: Heterogeneity in study design, outcome definitions, and resistance testing methods limited comparability across studies. Conclusions: Bedaquiline remains effective for DR-TB treatment in South Africa; however, emerging resistance and its molecular drivers pose a growing threat to regimen sustainability, including BPaL. Strengthened surveillance and standardized resistance testing are urgently needed. Full article

Background: Drug susceptibility testing in Mycobacterium species typically requires prolonged incubation periods during which the chemical integrity of antibiotics may not be maintained, potentially compromising the reliability and accuracy of minimum inhibitory concentration (MIC) determinations. Objectives: This study evaluated the in vitro stability of several antibiotics, including recently introduced agents (bedaquiline [BDQ], pretomanid, delamanid and clofazimine) used for treating multidrug-resistant mycobacteriosis (linezolid and moxifloxacin), and those commonly included in combination regimens (rifampicin, isoniazid, ethambutol and clarithromycin). Methods: Antibiotics were pre-incubated at 37 °C before MIC determination and those exhibiting two or more dilutions in MIC were further tested in combination with ascorbic acid (AA) and pyruvate (P). Results: All antibiotics demonstrated stability except BDQ, which showed significant MIC variation after pre-incubation, which was prevented when BDQ was combined with AA and P. Conclusions: These findings suggest that the combined use of AA and P may serve as an effective stabilizing strategy for BDQ during MIC determination. Full article

Multidrug-resistant tuberculosis is a major global health concern. Newer agents, including bedaquiline (BDQ), delamanid (DLM), pretomanid (PMD), and linezolid (LZD), are essential for treatment; however, the resistance mechanisms of these drugs remain poorly understood in South Korea. This study aimed to investigate correlations between phenotypic and genotypic resistance to these drugs using 49 clinical Mycobacterium tuberculosis isolates collected in South Korea between 2017 and 2022. The minimum inhibitory concentrations were determined using the 7H9 broth microdilution method, and whole-genome sequencing (WGS) results were compared with the May 2024 World Health Organization (WHO) mutation catalogue. Phenotypic drug susceptibility testing (pDST) revealed elevated MICs to BDQ in 12 isolates (24.5%), DLM in nine (18.4%), and PMD and LZD in two each (4.1%). No Group 1 or 2 resistance-associated mutations were detected in BDQ-, PMD-, or LZD-elevated-MIC isolates. A Group 2 mutation (fbiC_LoF) was observed in one DLM-elevated-MIC isolate, whereas fbiC_p.Ala855fs (WHO Group 2) mutations occurred in four susceptible isolates. These findings suggest resistance mechanisms beyond the current WHO catalog. Discrepancies between pDST and WGS highlight the need for integrated diagnostics and reinforce the importance of ongoing surveillance and refinement of mutation classification systems to improve genotypic resistance prediction. Full article

Tuberculosis (TB) remains a global public health emergency, with multidrug-resistant TB (MDR-TB) and rifampicin-resistant TB (RR-TB) posing critical challenges. Conventional longer regimens are characterized by suboptimal effectiveness, high toxicity, and poor tolerability. Consequently, there is an urgent demand for more effective, safer, shorter regimens with enhanced tolerability to replace traditional treatments. The present study aimed to systematically assess the effectiveness and safety of bedaquiline-containing modified shorter regimens (adaptations of the WHO-recommended 9–12-month bedaquiline-containing shorter regimen, with ethionamide, ethambutol, isoniazid, and pyrazinamide partially or fully substituted by linezolid, cycloserine/terizidone, and/or delamanid) for MDR/RR-TB. Databases (PubMed, Cochrane Library, Embase, and Web of Science) were searched up to 17 December 2025. Data on treatment success, adverse events, and patient characteristics were extracted. Heterogeneity was assessed using Cochrane Q test and I² statistic. Eleven studies involving 8166 patients were included. The pooled treatment success rate was 78.5% (95% CI: 0.69~0.87, I²: 98.45%; p = 0.00). The incidence of serious adverse events was 10.0%. Bedaquiline-containing modified shorter regimens may offer a potentially viable treatment option for MDR/RR-TB patients, giving an option for patients who are ineligible for standardized regimens. In order to verify these findings, further large-scale trials are required. Full article

Targeted next-generation sequencing (tNGS) closes the gap between point-of-care rapid tests and phenotypic drug susceptibility testing (pDST) in drug-resistant tuberculosis (DR-TB). The 2025 World Health Organization (WHO) consolidated guidelines and the operational handbook place tNGS after initial automated nucleic acid amplification tests (aNAATs) for the delivery of catalogue-linked molecular drug susceptibility testing (DST) for a broad drug panel, reserving whole-genome sequencing (WGS) and/or pDST for discordance resolution, confirmation, and surveillance. This review summarizes (i) the core tNGS principles and panel design; (ii) platform-specific workflows for Illumina and Nanopore, including direct-from-sample implementations and typical turnaround times; (iii) catalogue-based interpretation against the 2023 WHO Mycobacterium tuberculosis mutation catalogue, with emphasis on bedaquiline/clofazimine (BDQ/CFZ) resistance and management of uncertain variants; (iv) pooled accuracy and sources of genotype–phenotype discordance; and (v) practical requirements for bioinformatics, quality assurance/external quality assessment (QA/EQA), and standardized reporting. We summarize operational and economic considerations (throughput, batching, and network design) to clarify where tNGS adds value compared with alternative strategies and to outline priority research needs, including (i) performance standards for culture-free tNGS, (ii) robust heteroresistance detection, (iii) standardized variant curation, and (iv) data-sharing frameworks to refine genotype–phenotype links. When embedded within validated QA/EQA frameworks and catalogue-linked reporting systems, tNGS can shorten the time to effective therapy by rapidly informing fluoroquinolone (FQ) susceptibility and providing early, tiered resistance signals for newer agents (e.g., BDQ), with indeterminate findings prompting reflex pDST/WGS. Full article

Tuberculosis (TB) probably returned to being the world’s leading cause of death from a single infectious agent after three years during which it was replaced by COVID-19. Currently, there are two major, closely related challenges in TB treatment: a large number of cases of drug-resistant TB, as well as cases complicated by severe comorbidities. Materials and Methods: Our study included 219 patients with pulmonary multidrug-resistant TB (MDR-TB) who were treated in several clinics in St. Petersburg, Russian Federation. Of these patients, 47.0% had extensively drug-resistant TB (XDR-TB), and 48.4% had severe comorbidities. Univariate and multivariate exploratory analyses were performed to hypothesize factors affecting treatment success. Results: Both extensive drug resistance (XDR-TB) and the presence of comorbidity were significantly associated with a lower probability of successful treatment: OR = 0.56 (CI: 0.32–0.96, p = 0.033) and OR = 0.53 (CI: 0.30–0.91, p = 0.020), respectively. The use of bedaquiline was significantly associated with successful treatment in cases of XDR-TB: OR = 4.15 (CI: 1.32–16.20, p = 0.012). Only an insignificant opposite effect was identified for cases of non-XDR-TB: OR = 0.77 (p = 0.62). Resistance to thioamides was associated with unsuccessful treatment in cases complicated by comorbidity: OR = 0.46 (CI: 0.21–0.99, p = 0.044). Again, an only insignificant opposite effect was identified for cases without comorbidities: OR = 1.11 (p = 0.81). Almost all the patterns described above were replicated in the multivariate model. The following two differences with the univariate results were observed. First, the association between the use of bedaquiline and successful treatment became even more pronounced, and, as before, this was true only for XDR-TB: OR = 6.51 (CI: 1.98–26.04, p = 0.0036) for XDR-TB, and OR = 0.99 (p = 0.98) for non-XDR-TB. Second, the impact of comorbidities on treatment success remained significant only in conjunction with thioamide resistance. In addition, we found that the association between resistance to thioamides and unsuccessful treatment was especially pronounced in cases complicated by heart disease: OR = 0 (CI: 0–0.79, p = 0.0088). Conclusions: We confirmed that both XDR-TB and the presence of comorbidities are serious challenges in the treatment of tuberculosis. We also have reason to hypothesize that, first, bedaquiline can be a much more crucial component of therapy in cases of XDR-TB than in other cases of MDR-TB and, second, thioamides can play a positive role in cases complicated by comorbidities, especially by heart diseases. These findings should be considered as weak hypotheses that require further verification using independent data, as our analysis was exploratory rather than confirmatory. Full article

Tuberculosis (TB) is a global health challenge caused by Mycobacterium tuberculosis, with drug resistance, treatment toxicity, and treatment adherence challenges continuing to impede control efforts. The objective of this review is to explore current advancements in TB treatment, for both drug-sensitive and drug-resistant TB, focusing on pharmacologic regimens, diagnostics, and adjunctive therapies. For drug-sensitive TB, a 4-month rifapentine–moxifloxacin regimen has been proven to be non-inferior to the traditional 6-month standard, while optimized pyrazinamide dosing or faropenem substitution may improve culture conversion and reduce adverse events. In drug-resistant TB, regimens such as the bedaquiline, pretomanid, linezolid, and moxifloxacin have demonstrated efficacy with substantially shorter treatment duration; however, incidents of hepatotoxicity and linezolid-related neuropathy require careful monitoring. Adjunctive therapies, such as metformin, N-Acetylcysteine, aspirin, and statins, show promising effects in modulating host immunity and reducing long-term lung damage. Advances in diagnostics, including whole genome sequencing and CRISPR-based methods, are enabling rapid detection of resistance mutations and directed therapy. Vaccine development has advanced beyond the BCG vaccine to explore vaccines with enhanced immunogenicity or ones that are safe for immunocompromised patients. Implementation strategies such as video directly observed therapy are improving adherence; additionally, community-based, technology-supported interventions significantly improve TB knowledge and compliance. An integrated approach that combines optimized pharmacologic regimens, host-directed therapies, advanced diagnostics, and patient-centered public health strategies is essential to reduce TB incidence, long-term morbidity, and mortality. Full article

Tuberculosis remains a serious infectious disease that causes over 1.3 million deaths annually. Following the COVID-19 pandemic, the global incidence of tuberculosis has increased to 10.8 million cases. Pregnant women represent a particularly vulnerable population requiring tailored approaches to the prevention, diagnosis, and treatment of tuberculosis. SARS-CoV-2 infection may have impacted existing clinical protocols. Implementing updated methods of tuberculosis prevention, diagnosis, and treatment in pregnant women could help reduce adverse maternal and fetal outcomes. The aim of this review was to explore potential modifications in tuberculosis management among pregnant women in the post-COVID-19 era, including co-infection with SARS-CoV-2. Methods: A review was conducted, incorporating a systematic literature search across major international databases, including Medline, PubMed, Web of Science, Scopus, and Google Scholar. The search covered publications released between December 2019 and September 2024 and used targeted keywords such as “COVID-19” OR “SARS-CoV-2”, “tuberculosis” OR “TB” OR “latent tuberculosis infection” OR “pulmonary tuberculosis”, and “pregnancy” OR “pregnant women”. Results: Pregnant women living with HIV are at increased risk of developing tuberculosis, which can negatively affect both maternal and perinatal outcomes. Screening for tuberculosis is recommended for all HIV-positive pregnant women, even in the absence of clinical symptoms. Notably, immunological testing before and during pregnancy facilitates the timely and safe detection of tuberculosis infection, enabling preventive and therapeutic interventions during any stage of gestation and the early postpartum period, for the benefit of both mother and child. Drug–drug interactions play a significant role in tuberculosis management, both among anti-tuberculosis agents and with medications for comorbid conditions. Current knowledge of the pharmacokinetics and pharmacodynamics of antituberculosis agents, coupled with therapeutic drug monitoring, supports the development of individualized and effective treatment regimens, which are particularly critical for pregnant patients. Recommendations for managing tuberculosis in pregnant women after COVID-19 infection include measuring D-dimer levels, performing echocardiography, and consulting cardiologists to prevent treatment-related complications. Conclusions: Pregnant women represent a distinct subgroup of tuberculosis patients requiring individualized management. Changes observed in tuberculosis progression and treatment responses in pregnant women before and after SARS-CoV-2 infection should inform therapeutic choices, especially in cases of drug-resistant tuberculosis treated with bedaquiline. COVID-19 has been associated with increased cardiovascular risk, which may heighten the likelihood of adverse drug reactions in this population, especially given the limited therapeutic options. Further research is required to assess the long-term outcomes of latent tuberculosis infection in pregnant women and to evaluate the safety and efficacy of novel regimens for drug-resistant TB during pregnancy. Full article

Bedaquiline is known to shorten the duration of therapy of tuberculosis but has limitations, e.g., poor solubility and adverse effects such as prolongation of the QT interval. In this study, bedaquiline was incorporated into an inherently targeted nanosystem for improved permeation of the drug, with ex vivo diffusion studies performed to investigate its penetration. The bedaquiline-loaded mannan–chitosan oligosaccharide lactate nanoparticles were prepared by a one-step ionic gelation probe sonication method. A PermeGear 7-in-line flow-through diffusion system was used for the ex vivo diffusion studies across porcine and human pericardia. Bedaquiline-loaded nanoparticles with a particle size and potential of 192.4 nm and 40.5 mV, respectively, were obtained. The drug-loaded mannan–chitosan nanoparticles had an encapsulation efficacy of 98.7% and drug loading of 0.6%. Diffusion data indicated a steady-state flux of 2.889 and 2.346 µg.cm⁻².min⁻¹ for porcine and human pericardia, respectively. The apparent permeability coefficients were calculated to be 2.66 × 10⁻⁴ cm.min⁻¹ and 2.16 × 10⁻⁴ cm.min⁻¹ for porcine and human pericardia, respectively. The lag phases were 52.72 min and 0 min for porcine and human pericardia, respectively. The drug permeation indicated a consistent and linear diffusion pattern across both porcine and human pericardia, additionally approving the porcine pericardium as a great comparable tissue to human tissue for pericardial studies. This study is the first to demonstrate ex vivo diffusion of bedaquiline-loaded, macrophage-targeted chitosan–mannan nanoparticles across both human and porcine pericardia, representing a novel platform for disease-targeted, localized treatment of TB pericarditis. Full article