Background/Objectives: Short-course regimens (SCRs) are increasingly used to treat drug-resistant tuberculosis (DR-TB), but data on post-treatment recurrence remain limited. We aimed to estimate the frequency of post-treatment recurrence after SCRs and compare recurrence between SCRs and comparator regimens. Methods: We conducted a systematic review and meta-analysis of clinical studies reporting treatment duration, post-treatment follow-up, and recurrent tuberculosis episodes after SCRs for DR-TB. The primary single-arm analysis used a binomial-normal random-effects generalized linear mixed model (GLMM) based on r/A, retaining zero-event cohorts without a continuity correction. Comparative analyses used pooled risk ratios (RRs) and person-time-adjusted incidence rate ratios (IRRs). Results: Twenty-five studies contributed 26 SCR cohorts. In the primary analysis, 98 recurrent tuberculosis episodes occurred among 6954 patients; the pooled proportion was 1.24% (95% confidence interval [CI], 0.79–1.93%; 95% prediction interval, 0.24–6.21%). The pooled proportion was 1.20% (95% CI, 0.70–2.03%) for fully oral SCRs, 1.57% (0.85–2.85%) for pretomanid-containing SCRs, 1.55% (0.93–2.56%) for SCRs lasting ≤ 39 weeks, and 1.95% (1.20–3.15%) for SCRs lasting ≤ 36 weeks. In the overall comparative analysis, no statistically significant difference in post-treatment recurrence was observed between SCRs and comparator regimens: the pooled RR was 1.35 (95% CI, 0.34–5.40), and the person-time-adjusted IRR was 1.25 (95% CI, 0.50–3.15). In the randomized controlled trial (RCT) subset, the pooled RR indicated a higher recurrence risk with SCRs (RR, 2.72; 95% CI, 1.25–5.89), whereas the corresponding person-time-adjusted estimate did not show a statistically significant difference (IRR, 1.66; 95% CI, 0.81–3.43). This divergence indicates that comparative estimates are sensitive to how post-treatment follow-up duration is accounted for. Meta-regression identified no statistically significant associations between recurrence frequency and the examined cohort-level clinical characteristics. The certainty of evidence, assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, was low for the estimated recurrence frequency after fully oral SCRs, very low for the subgroup estimates, and low for the comparative estimates. Conclusions: These findings indicate a low frequency of post-treatment tuberculosis recurrence after SCRs and support the durability of treatment outcomes achieved with these regimens. However, substantial between-study heterogeneity and differences in post-treatment follow-up limit the interpretation of the pooled estimate as a uniform long-term recurrence risk. Further studies with standardized follow-up beginning at treatment completion are needed to provide more precise estimates of long-term outcomes after SCRs.

Tuberculosis remains one of the leading infectious diseases worldwide, which is why new approaches are being developed as a foundation for future diagnostic methods. One promising strategy relies on porphyrins as biomarkers for the detection of Mycobacterium tuberculosis using fluorescence spectroscopy. Previous attempts have been made to detect microorganisms based on their porphyrin production. However, insufficient endogenous porphyrin production limits the applicability of this approach for mycobacterial detection. As a proof-of-principle study, we investigated the feasibility of using exogenous precursors to enhance porphyrin accumulation with the aim of detecting mycobacterial growth by means of fluorescence spectroscopy. The introduction of these precursors resulted in a significantly higher fluorescence signal intensity, making it possible to detect Mycobacterium tuberculosis and identify potential contamination.

Background: Despite extensive development of liposomal antibiotics, the structural determinants governing their stability, release, and biological activity remain poorly understood. This study investigated how the cholesterol content and drug-to-lipid ratio affect membrane organization and thereby determine the physicochemical and biological properties of linezolid-loaded liposomes. Methods: Nine liposomal formulations, varying in their cholesterol content (10–30 wt%) and drug-to-lipid ratios (1–5%), were prepared by thin-film hydration. Membrane organization was analyzed by ATR-FTIR spectroscopy and principal component analysis. Liposomes were further characterized by particle size, ζ-potential, encapsulation efficiency, storage stability, in vitro release in phosphate buffer with and without bovine serum albumin, antibacterial activity against B. subtilis, and antimycobacterial activity in an ex vivo PBMC-derived Mycobacterium tuberculosis granuloma model. Results: The cholesterol content and drug-to-lipid ratio markedly altered membrane interfacial organization, particularly the hydration of the carbonyl and phosphate regions. These structural changes correlated with differences in storage stability, protein-responsive release, and antibacterial activity. Functional behavior was non-monotonic, as 30-L showed the highest overall storage stability, while the apparent release depended jointly on the cholesterol content, drug loading, and medium. BSA altered the composition-dependent release pattern instead of producing a uniform effect. In the exploratory granuloma model, the formulations 10-S, 10-L, and 30-M reduced M. tuberculosis CFU by >99%, whereas free linezolid produced approximately 60% inhibition. Conclusions: Membrane interfacial organization is a key determinant of the functional performance of liposomal linezolid, establishing a structure–property–function relationship that provides a mechanistic basis for the rational design of liposomal antibiotic delivery systems for tuberculosis therapy.

The global spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) demands fundamentally new approaches combining diagnostic speed and therapeutic efficacy. Within the strategy of personalised medicine, the lytic mycobacteriophage D29 represents a promising tool for both phenotypic drug susceptibility testing and the targeted delivery of therapeutic agents to the infection site. We developed a two-component platform based on D29: (1) a diagnostic test system combining a rapid anti-mycobacterial susceptibility testing (AMST) module, which detects phage D29 replication in drug-resistant isolates via multiplex real-time PCR; and (2) a liposomal therapeutic formulation. Therapeutic efficacy was evaluated in C57BL/6 mice (n = 55) with experimental pulmonary tuberculosis receiving liposomal D29 either aerosolised (inhalation chamber) or intranasally. Bacterial burden (CFU/lung) was assessed at days 3 and 14 post-therapy. Pharmacokinetics were studied in 90 mice using the double-layer agar method. The diagnostic test showed an average sensitivity and specificity of 90.0% and 96.3% across nine drugs, with results available within five days. The lyophilised components and phage remained stable for 12 months. Aerosol therapy demonstrated a trend towards a higher efficacy compared to intranasal administration: the median CFU/lung at day 3 was 107 (i.e., one hundred and seven) vs. 23,500 (control 65,000); 60% of aerosol-treated animals achieved ≤200 CFU/lung (not statistically significant, p = 0.089). Both routes significantly outperformed controls (p < 0.01 and p < 0.05). Pharmacokinetics revealed exclusive lung tropism with peak concentrations at 5 min (1.9 × 10³–5.1 × 10⁴ PFU/organ) and phage levels falling below the limit of detection (<5 × 10³ PFU/organ) within 24 h. Infected lungs showed significantly higher phage titres than uninfected ones, indicating in vivo replication. Safety studies showed no significant toxicity, immunogenicity, or local irritation. The integrated D29-based platform represents a comprehensive, integrated diagnostic–therapeutic solution covering the full “diagnosis–therapy” cycle. The test system provides rapid phenotypic drug susceptibility profiling, while the liposomal phage demonstrates potent therapeutic activity and favourable pharmacokinetics, supporting its clinical translation.

Tuberculous meningitis (TBM) is a critically severe form of extrapulmonary tuberculosis in pediatric patients. Presents a significant diagnostic challenge during the early stages of clinical manifestation. Delayed recognition of meningeal tuberculous inflammation leads to the involvement of the brain parenchyma (encephalitis) and may result in irreversible neurological sequelae. Objective: To evaluate the clinical features, the spectrum of complications, and the outcomes of tuberculous meningitis in pediatric patients under current epidemiological conditions. Materials and Methods: A retrospective analysis of 21 medical records was conducted for pediatric patients aged 3 months to 17 years (mean age: 6.7 ± 5.8 years) with a confirmed TBM diagnosis. The study included pediatric patients treated in the tuberculosis department or evaluated through the telemedicine consultation system between January 2017 and May 2025. Results: A history of contact with a tuberculosis patient was established in 62% (13/21) of cases. At initial presentation, fever was recorded in 67% (14/21) of patients, headache and nausea/vomiting in 52% (11/21), and meningeal signs in 38% (8/21). The majority of patients (52%, 11/21) had not received BCG vaccination. Mycobacterium tuberculosis (MBT) was identified in 19 patients (90%). MTB DNA was detected in the cerebrospinal fluid (CSF) in 79% of patients (15/21). Drug resistance (DR) was confirmed in 57.9% of patients (11/19), including MDR/XDR strains in 81.8% (9/11) of the DR subgroup. Complications included motor deficits in 38% (8/21), hydrocephalus in 47.6% (10/21), and epileptic syndrome in 19% (4/21). Four patients (19%) with an unfavorable outcomes were transitioned to palliative care. Conclusion: In pediatric patients; TBM delayed diagnosis results in a more severe clinical course characterized by the development of profound neurological deficits. This study demonstrates that TBM has evolved from a predominantly meningeal disease into a severe form of meningoencephalitis; frequently accompanied by hydrocephalus; epilepsy; and motor deficits. Notably; seizure disorder serves as a critical predictor of an unfavorable outcome. These findings underscore the urgent need to optimize early diagnostic strategies within general healthcare networks.

Tuberculous meningitis (TBM) is a critically severe form of extrapulmonary tuberculosis in pediatric patients, presenting a significant diagnostic challenge during the early stages of clinical manifestation. Delayed recognition of meningeal tuberculous inflammation leads to the involvement of the brain parenchyma (encephalitis) and may result in irreversible neurological sequelae. Objective: To evaluate the clinical features, the spectrum of complications, and the acute outcomes of tuberculous meningitis in pediatric patients managed at a tertiary reference center. Materials and Methods: A retrospective observational study of 21 medical records was conducted for pediatric patients aged 3 months to 17 years (mean age: 6.7 ± 5.8 years) with a confirmed TBM diagnosis. The study included pediatric patients treated in the inpatient pediatric department (n = 6) or evaluated through the national telemedicine consultation system (n = 15) between 2017 and 2025. Results: A history of contact with a tuberculosis patient was established in 62% (13/21) of cases. At initial presentation, fever was recorded in 67% (14/21) of patients, nausea and/or vomiting in 52% (11/21), headache in 33% (7/21), and meningeal signs in 38% (8/21). The majority of patients (52%, 11/21) had not received BCG vaccination. Mycobacterium tuberculosis (MTB) was microbiologically confirmed in 19 patients (90.5%). MTB DNA was detected in the cerebrospinal fluid (CSF) in 71.4% of all patients (15/21; 78.9% of confirmed cases). Drug resistance (DR) was confirmed in 47.4% of confirmed patients (9/19; 42.9% of the total cohort), comprising MDR (15.8%, 3/19), pre-XDR (15.8%, 3/19), and XDR (15.8%, 3/19) strains. Neurological complications included hydrocephalus in 47.6% (10/21), motor deficits in 38.1% (8/21), and epileptic syndrome in 19.0% (4/21). In-hospital mortality was 0%, while four patients (19.0%) with critically severe irreversible brain damage were transitioned to palliative care. Conclusion: In this tertiary pediatric cohort, TBM presented predominantly as a severe form of meningoencephalitis with extensive brain parenchymal involvement and high rates of systemic dissemination, frequently complicated by hydrocephalus, motor deficits, and seizures. Epileptic seizures showed an exploratory statistical trend toward an association with unfavorable neurological outcomes (p = 0.052). These findings underscore the urgent need to optimize early diagnostic strategies within general healthcare networks.