Treatment of pre-extensively drug-resistant tuberculosis in a critically ill patient using bedaquiline, pretomanid, and linezolid therapy in Canada: A brief report.

内容摘要

Pre-extensively drug-resistant tuberculosis (pre-XDR-TB) infections are rare in Canada. Drug therapies to treat pre-XDR TB are limited and acquisition of World Health Organization guideline regimens that are not marketed in Canada pose delays in patient care. Our report describes the case of a critically ill patient with pre-XDR TB and their journey to recovery using bedaquiline, pretomanid, and linezolid (BPaL) therapy. In 2024, a 20-year-old international student from India with no past medical history presented to hospital complaining of respiratory symptoms and had evidence of cavitary findings on chest imaging. While hospitalized, sputum samples reported acid fast bacilli (AFB) on smear. Subsequently, Mycobacterium tuberculosis complex DNA was detected using molecular methods and confirmed in culture. The standard four-drug regimen was initiated after the positive AFB report. Upon staged availability of drug susceptibility results, drug therapy was altered as the strain was resistant to the entire empiric regimen. Due to challenges in the early detection of resistance, the patient clinically worsened resulting in mechanical ventilation. The patient was converted from four-drug intravenous therapy to BPaL therapy obtained through Health Canada's Special Access Program on hospital day 70. The patient reached non-infectious status on hospital day 200. This case highlights clinical challenges encountered in the management of pre-XDR TB in Canada and describes the successful use of BPaL therapy in a mechanically ventilated patient. In Canada, drug-resistant TB is rarely encountered. Consequently, there is limited access to rapid susceptibility testing in hospital laboratories and obtaining non-Health Canada approved medications is procedurally complex. Both of these issues cause significant delays in patient treatment. We present the case of a young female studying in Canada from India who developed signs and symptoms suggestive of a TB infection. The patient was started on usual TB medications used in Canada, but after a lengthy wait it was discovered that the patient's infection was caused by a strain that was resistant to all four of the TB medications she had been started on. While in hospital awaiting further TB testing results, the patient’s condition worsened, and they required transfer to the intensive care unit (ICU) where they were placed on a ventilator to help maintain oxygen levels. An alternative treatment regimen consisting of four intravenous medications was initiated while the hospital pharmacy service worked to obtain two medications that are not approved for use in Canada. The patient was started on the optimal treatment regimen 70 days from when they first presented to hospital due to challenges in resistance testing and medication acquisition. After a lengthy hospitalization, the patient clinically improved and, once deemed no longer infectious, returned home to India. This patient case highlights some of the challenges Canadian clinicians face when trying to manage patients with drug resistant TB and discusses potential solutions. La tuberculose pré-ultrarésistante (TB-pré-UR) est rare au Canada. Les médicaments pour la traiter sont limités et l'acquisition de ceux recommandés par l'Organisation mondiale de la Santé qui ne sont pas commercialisés au Canada retardent les soins aux patients. Ce rapport décrit le cas d'une personne gravement malade atteinte de TB-pré-UR et de son parcours vers le rétablissement grâce à un traitement à la bédaquiline, au prétomanide et au linézolide (BPaL). En 2024, une personne de 20 ans originaire de l'Inde venue étudier au pays et qui n'avait pas de problèmes médicaux a consulté à l'hôpital à cause de symptômes respiratoires. L'imagerie pulmonaire a révélé des lésions cavitaires. Pendant l'hospitalisation, le frottis des expectorations a démontré la présence de bacilles acido-alcoolo-résistants (BAAR). Par la suite, des méthodes moléculaires ont détecté la présence de l'ADN complexe du Mycobacterium tuberculosis a, ensuite confirmée par cultures. La posologie standard de quatre médicaments a été entreprise après le résultat positif de BAAR. Après l'obtention graduelle des résultats de susceptibilité aux médicaments, la pharmacothérapie a été modifiée, puisque la souche était résistante à la posologie empirique. En raison des difficultés liées à la détection rapide de la résistance, l’état clinique de ce cas s'est aggravé et a nécessité une ventilation mécanique. Au 70e jour d'hospitalisation, les quatre médicaments intraveineux ont été remplacés par un traitement par BPaL obtenu grâce au Programme d'accès spécial de Santé Canada. L’état non infectieux a été atteint le 200e jour d'hospitalisation. Ce cas fait ressortir les difficultés cliniques liées à la prise en charge de la TB-pré-UR au Canada et décrit l'utilisation réussie du traitement par BPaL chez une personne sous assistance ventilatoire mécanique.