Real-life use of delamanid: results from the European post-authorisation safety study.

BACKGROUND: A post-authorisation safety study (PASS) on delamanid (DLM) was conducted as part of a post-approval commitment to the European Medicines Agency. The aim of this study was to evaluate the use of DLM in a real-life setting, its safety, and treatment outcomes in patients with multidrug-resistant TB (MDR-TB). METHODS: This was a prospective, multicentric, non-interventional study conducted in the European Union. MDR-TB Regimen selection and patient monitoring were conducted in accordance with existing medical practices. Data on the use of DLM, related adverse events, and treatment outcomes were collected for up to 30 months after the first DLM dose. Descriptive summary statistics were used for continuous and categorical variables. RESULTS: Out of 86 patients, one had extrapulmonary TB. Two-thirds of the patients were treated with DLM for more than 24 weeks. The most frequent adverse drug reaction to DLM was QT interval prolongation. Resistance to DLM was detected in one patient during treatment. The treatment success rate was 77%. CONCLUSION: No new safety concerns were revealed, including in patients treated with DLM for more than 24 weeks. QT interval prolongations were well managed and did not lead to any clinically significant cardiac effects. The treatment outcomes were in line with the WHO target for Europe.

CONTEXTE: Une étude de sécurité post-autorisation (PASS) sur le délamanide (DLM) a été menée dans le cadre d'un engagement post-approbation auprès de l'Agence européenne des médicaments. L'objectif de cette étude était d'évaluer l'utilisation du DLM dans un contexte réel, son innocuité et les résultats du traitement chez les patients atteints de TB multirésistante (MDR-TB). MÉTHODES: Il s'agissait d'une étude prospective, multicentrique et non interventionnelle menée dans l'Union européenne. La sélection du schéma thérapeutique de la MDR-TB et le suivi des patients ont été effectués conformément aux pratiques médicales existantes. Les données sur l'utilisation du DLM, les effets indésirables connexes et les résultats du traitement ont été recueillies jusqu'à 30 mois après la première dose de DLM. Des statistiques sommaires descriptives ont été utilisées pour les variables continues et catégorielles. RÉSULTATS: Sur 86 patients, un avait une TB extrapulmonaire. Les deux tiers des patients ont été traités avec du DLM pendant plus de 24 semaines. L'effet indésirable le plus fréquent du DLM était l'allongement de l'intervalle QT. Une résistance au DLM a été détectée chez un patient pendant le traitement. Le taux de réussite du traitement était de 77%. CONCLUSION: Aucun nouveau problème de sécurité n'a été révélé, y compris chez les patients traités par le DLM pendant plus de 24 semaines. Les allongements de l'intervalle QT ont été bien gérés et n'ont pas entraîné d'effets cardiaques cliniquement significatifs. Les résultats du traitement étaient conformes à l'objectif de l'OMS pour l'Europe.

Thoracic manifestations of tularaemia: a case series.

BACKGROUND: Tularaemia is a zoonotic disease caused by Francisella tularensis, a highly virulent bacterium that affects humans and small wild animals. It is transmitted through direct contact with infected animals or indirectly through contaminated soil, water or arthropod bites (e.g. ticks). Primary thoracic manifestations of tularaemia are infrequent and, therefore, a diagnostic challenge for clinicians. METHODS: We report six tularaemia cases with exclusively thoracic involvement diagnosed in a clinic for pulmonary diseases in Bavaria between 10/2020 and 02/2022. RESULTS: All patients lived or were active in rural areas, four reported a recent tick bite. All patients presented with thoracic lymphadenopathy and pulmonary tumours or consolidations; all underwent bronchoscopy with EBUS-TBNA of lymph nodes, three lung biopsies as well. Five patients showed inflammatory changes in the endobronchial mucosa. The main histological findings were necrotic epithelioid granulomas with remarkable granulocyte infiltration. All cases were identified by positive serology, five by PCR (here identification of F.t. ssp. Holarctica) from biopsy as well. As first-line therapy, oral ciprofloxacin was given (5/6); in 2/6 cases, a combination of quinolone-rifampicin was given. CONCLUSIONS: Pulmonary tularaemia may occur after tick bites and without extrathoracic manifestations. In patients who present with thoracic lymphadenopathy and pulmonary consolidations and who are exposed to increased outdoor activities, tularaemia should be included in the diagnostic pathway. Histologically, the presence of neutrophil-granulocyte infiltrations might help to distinguish tularaemia from other granulomatous infections, e.g. tuberculosis. The combination of quinolone-rifampicin rather than i.v. gentamicin reduced length of hospital stay in two patients.

[Diffuse pulmonary meningotheliomatosis]. / Diffuse pulmonale Meningotheliomatose.

In two patients with bilateral micronodular pulmonary changes a diffuse pulmonary meningotheliomatosis was found. A 73-year-old woman presented with bilateral disseminated miliary pulmonary nodules as a radiological incidental finding. The surgical lung biopsy showed multiple tiny nodular proliferations meningothelial-like cells, corresponding "minute pulmonary meningothelial-like nodules", MPMN. A 60-year-old lady with similar radiological findings showed also proliferations of meningothelial-like cells in a transbronchial cryo-biopsy. These lesions are well known to pathologists as curious isolated incidental findings on histological examination of lung specimens. The here described diffuse form of these changes is very rare; its knowledge is important for the differential diagnosis with neoplastic proliferations and other diffuse parenchymal diseases of the lung. This rare diagnosis is made on histological grounds and is also possible in transbronchial biopsies when careful correlation with clinical and radiological data, knowledge of the entity and adequate specimens are provided.