Simone Tunesi

Background: Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide, while infections from non-tuberculous mycobacteria (NTM) represent a growing public health threat. In its 20th year of activity, the Tuberculosis Network European Trials group (TBnet; www.tbnet.eu) is one of the leading research networks in Europe. In this review, we summarize the main advances in TB and NTM that occurred in 2025. Methods: We conducted a non-systematic review of articles published in 2025, with a strong emphasis on research with current or potential impact on clinical practice. We also selected the most impactful papers regarding the management of adult TB, pediatric TB, and NTM infections. Results: Members of the TBnet Steering Committee summarize the main advances in their areas of interest, including epidemiology, pathogenesis, prevention, diagnosis, treatment, pediatric TB, and NTM infections. We also include a summary of future research priorities. Conclusions: The year 2025 presented many exciting advancements in almost all fields of mycobacterial science. This article provides an expert-based, clinically orientated summary of the main new findings in the TB and NTM fields and aims to provide an updated overview of the state of the art in those areas.

Background: Morbidity associated with central nervous system tuberculosis (CNS TB) remains high due to persistent inflammation despite standard-of-care (SOC) treatment, including antituberculosis therapy and corticosteroids. Tumour necrosis factor alpha (TNF-α) is a key cytokine driving this inflammatory response, and a limited number of case reports suggest that TNF-α inhibitor may improve outcomes. We report the 1-year outcome of a cohort of consecutive patients treated with infliximab for severe CNS TB. Methods: Following the guidance provided by the French Tuberculosis Consilium, a standardized regimen of intravenous infliximab at 5 mg/kg per dose was used to treat CNS TB unresponsive to SOC. We retrospectively included consecutive patients who received at least 1 infliximab injection for CNS TB from 2017 to September 2021. Results: Eighteen patients with CNS TB, 94% with tuberculous meningitis, were included. Most had severe disease: 82% were classified as British Medical Research Council grade II or III, and 44% required intensive care unit admission. All demonstrated clinical and radiological worsening despite SOC; in 89% due to paradoxical reaction. At infliximab initiation, symptoms remained disabling, with a median modified Rankin Scale (mRS) score of 3.5 (interquartile range, 3-4). One month after the first infusion, 38% showed improved mRS scores, increasing to 78% at 1 year. One-year survival was 94%; one death occurred 12 months after a single infliximab dose and was unrelated to TB treatment. Conclusion: Infliximab may represent a promising adjunctive treatment for CNS TB unresponsive to SOC, including paradoxical reaction. Prospective studies are needed to confirm these findings.

Preventing the progression of a drug-resistant tuberculosis (DR-TB) infection to disease is an important pillar of the DR-TB elimination strategy. International guidelines have recently proposed fluoroquinolones for tuberculosis preventive therapy (TPT) in DR-TB contacts, although the available evidence is low quality. The pooled data from small observational studies suggest that a fluoroquinolone-based TPT is safe, effective and cost-effective as a preventive treatment in DR-TB contacts. Three clinical trials are currently ongoing to generate higher quality evidence on the efficacy of levofloxacin and delamanid as a DR-TB preventive therapy. Additional evidence is also needed, regarding TPT treatment in fluoroquinolone-resistant-TB contacts, patient and health care worker perceptions on DR-TB preventive therapy for contacts, and the service delivery models to increase DR-TPT access. This state-of-the-art review presents the current literature on TPT for contacts of DR-TB cases, focusing on the available evidence and international guidelines.