Bedaquiline plus delamanid for XDR tuberculosis
We read with interest the correspondence by Caitlin Reed and colleagues, reporting a patient with a severe case of extensively drug-resistant (XDR) tuberculosis who was treated with bedaquiline and subsequently denied delamanid because of concerns over additive cardiac toxic effects.1 Here we report the case of a man with XDR tuberculosis who was treated with a regimen containing bedaquiline and delamanid in combination.
A 20-year-old man from Democratic Republic of the Congo was diagnosed with pulmonary tuberculosis in October, 2014. Sputum smears were positive. Cultures confirmed an XDR Mycobacterium tuberculosis strain. On the basis of genotypic and phenotypic drug susceptibility testing, an individualised combination of ethambutol, para-aminosalicylic acid, linezolid, cycloserine, ethionamide, and bedaquiline was initiated with directly observed treatment. After some initial improvement, the patient showed clinical and radiological worsening. In March, 2015, after the consilium organised by the French National Reference Center for Mycobacteria, a pulmonary lobectomy was done and the patient was initiated on a new tuberculosis treatment regimen under close medical supervision: ethambutol, para-aminosalicylic acid, linezolid, and bedaquiline to which delamanid, imipenem, and amoxicillin plus clavulanic acid were added. Serum potassium, calcium, magnesium, and albumin were measured before treatment initiation. An electrocardiography was done before treatment, and repeated twice a week during the first month, once a week for 2 months, and twice a month thereafter. After 6 months of treatment the patient had favourable clinical, microbiological, and radiological responses. No QT interval prolongation was observed. No other known adverse events were reported except nausea.
This is, to our knowledge, the first patient with XDR tuberculosis in whom a bedaquiline–delamanid combination has been initiated. The combination was initiated in a patient in whom an effective treatment cannot be designed, in the consideration that its potential life-saving benefits outweigh its unknown adverse event risks; in a department in which more than 100 tuberculosis cases a year are admitted to hospital, of which 14 cases are multidrug-resistant or XDR disease; after a multisciplinary consultation at the national level; and after patient's informed consent. Conditions for this combination use described by Alberto Matteelli and colleagues2 were therefore fulfilled. Moreover, this combination was initiated under close cardiac monitoring and was well tolerated over a 6 month period. These data need to be confirmed in a larger number of patients and ideally in clinical trials. In the meantime, from an individual and societal perspective, compassionate use of these combinations should not be denied to specific patients if conditions such as those enumerated by Matteelli and colleagues2 are respected.
NV has received grants from Janssen, outside the submitted work. YY has received personal fees from AbbVie, Bristol-Myers Squibb, Gilead, MSD, Roche, Johnson & Johnson, ViiV Healthcare, Pfizer, and Janssen for board membership, and for payment for development of educational presentation outside the submitted work. All other authors declare no competing interests.
References
- Reed, C, Mason, L, Cox, H, Seaworth, B, Lessem, E, and Furin, J. Compassionate and optimum use of new tuberculosis drugs. Lancet Infect Dis. 2015; 15: 1131
| Summary| Full Text| Full Text PDF - Matteelli, A, D'Ambrosio, L, Centis, R, Tadolini, M, and Migliori, GB. Compassionate and optimum use of new tuberculosis drugs. Lancet Infect Dis. 2015; 15: 1131–1132
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Source: The Lancet Infectious Diseases
