Isoniazid-monoresistant tuberculosis (HR-TB) is the most prevalent form of drug-resistant TB worldwide and in France and is associated with poorer treatment outcomes compared with drug-susceptible TB (DS-TB). The objective of this study was to determine the characteristics of HR-TB patients in France and to compare outcomes and safety of treatment for HR-TB and DS-TB. We performed a case-control multicenter study to identify risk factors associated with HR-TB and compare treatment outcomes and safety between HR-TB patients and DS-TB patients. Characteristics of 99 HR-TB patients diagnosed and treated in the university hospitals of Paris, Lille, Caen and Strasbourg were compared with 99 DS-TB patients. Female sex (OR = 2.2; 1.0-4.7), birth in the West-Pacific World Health Organization region (OR = 4.6; 1.1-18.7) and resistance to streptomycin (OR = 77.5; 10.1-594.4) were found to be independently associated with HR-TB. Rates of treatment success did not differ significantly between HR-TB and DS-TB. Factors associated with HR-TB are not significant enough to efficiently screen TB patients at risk of HR-TB. The systematic implementation of rapid molecular testing on clinical samples remains the only effective way to make the early diagnosis of HR-TB and adapt treatment.

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.

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.