Treatment outcomes of bedaquiline-resistant tuberculosis: a retrospective and matched cohort study
Notice bibliographique
Résumé
BACKGROUND: Rising prevalence of bedaquiline resistance undermines benefits from this life-saving drug for rifampicin-resistant tuberculosis (RR tuberculosis). Despite increasing awareness, patient-level outcomes for bedaquiline-resistant tuberculosis have not been well characterised and case management has been poorly defined. METHODS: We did a retrospective cohort study of bedaquiline-resistant tuberculosis with matched RR tuberculosis controls at a tuberculosis referral hospital in East London, South Africa. Cases included patients aged 13 years or older with a phenotypic bedaquiline-resistant Mycobacterium tuberculosis isolate identified between Jan 1, 2018 and June 30, 2023. Controls with confirmed bedaquiline-susceptible tuberculosis, matched 1:1 by baseline culture status, age, and HIV status, were selected from a prospective observational study conducted during an overlapping period at the same facility. Primary outcomes included time to sputum culture conversion (SCC), a modified WHO-defined unfavourable outcome, and tuberculosis-free survival (alive, with SCC, and in care or treatment completed) up until 18 months. Adjusted analyses used Cox proportional hazards and logistic regression models. FINDINGS: 82 patients with bedaquiline-resistant tuberculosis were included, 57 (70%) of whom were HIV positive. Bedaquiline was prescribed for 72 (88%) of 82 patients and meropenem (plus amoxicillin-clavulanate) for 32 (39%) of 82. Together with bedaquiline, the most frequently prescribed drugs included clofazimine, linezolid, and terizidone. Median time to SCC after treatment initiation was 175 days (IQR 100-254) in the bedaquiline-resistant cohort and 32 days (30-42) in matched controls. In the analysis of the combined cohorts, bedaquiline resistance (adjusted hazard ratio 0·03, 95% CI 0·0023-0·29, p=0·003) was associated with longer time to SCC when adjusted for baseline microscopy grade and baseline fluoroquinolone resistance. WHO treatment outcomes in those with bedaquiline-resistant tuberculosis were unfavourable in 54 (67%) of 81 patients, driven by treatment failure in 35 (43%) of 81. At 18 months, 43 (52%) of 82 patients had reached tuberculosis-free survival, 19 (23%) of 82 had died, and 50 (79%) of 63 survivors were still on treatment. INTERPRETATION: Current treatment options for bedaquiline-resistant tuberculosis result in prolonged therapy, delayed microbiological responses, and poor clinical outcomes. Implementation of more rapid resistance testing, including targeted next-generation sequencing, and access to novel treatment options within randomised controlled trials for bedaquiline-resistant tuberculosis, are priorities for tuberculosis programmes. FUNDING: The South African Medical Research Council.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».