bedaquiline and Peripheral-Nervous-System-Diseases

Extensively drug-resistant tuberculosis (XDR TB) is a very serious form of tuberculosis that is burdened with a heavy mortality toll, especially before the advent of new TB drugs. The Democratic Republic of the Congo (DRC) is among the countries most affected by this new epidemic.. A retrospective analysis was performed of the records of all patients with pre- and extensively drug-resistant tuberculosis hospitalized from January 1, 2015 to December 31, 2017 and monitored for at least 6 months to one year after the end of their treatment in Kinshasa; an individualized therapeutic regimen with bedaquiline for 20 months was built for each patient. The adverse effects were systematically monitored.. Of the 40 laboratory-confirmed patients, 32 (80%) patients started treatment, including 29 preXRB and 3 XDR TB patients. In the eligible group, 3 patients (9.4%) had HIV-TB coinfections. The therapeutic success rate was 53.2%, and the mortality rate was 46.8% (15/32); there were no relapses, failures or losses to follow-up. All coinfected HIV-TB patients died during treatment. The cumulative patient survival rate was 62.5% at 3 months, 53.1% at 6 months and 53.1% at 20 months. The most common adverse events were vomiting, Skin rash, anemia and peripheral neuropathy.. The new anti-tuberculosis drugs are a real hope for the management of Drug Resistant tuberculosis patient and other new therapeutic combinations may improve favorable outcomes.

Topics: Adolescent; Adult; Aged; Anemia; Antitubercular Agents; Cost of Illness; Democratic Republic of the Congo; Diarylquinolines; Drug Administration Schedule; Drug Therapy, Combination; Exanthema; Extensively Drug-Resistant Tuberculosis; Female; Humans; Male; Middle Aged; Peripheral Nervous System Diseases; Retrospective Studies; Survival Rate; Treatment Outcome; Vomiting; Young Adult

Drug-resistant tuberculosis is an increasing healthcare challenge. Drug regimen building demands the use of different therapeutic groups, many of which harbor neurotoxicity as a side-effect, whether central or peripheral. Peripheral neuropathy is a major concern as it tends to be severe and usually irreversible. Anti-tubercular drugs that may contribute to peripheral neuropathy include INH, ethambutol, linezolid, cycloserine and para-amino salicylic acid. This potential adverse effect must be balanced against the intrinsically grave prognosis that drug resistant tuberculosis harbors. We present such a clinically challenging case of a 25 years-old female with extremely drug resistant tuberculosis whose treatment necessitated the use of several neurotoxic anti-tubercular drugs, leading to severe sensory peripheral neuropathy who did not improve despite the withdrawal of culprit drugs. She developed positive and negative sensory symptoms in both lower limbs. Nerve conduction studies were suggestive of sensory neuropathy affecting both lower limbs. Alternate causes of peripheral neuropathy including HIV, vasculitis, B12 deficiency and diabetes were ruled out. Despite drug withdrawal, the patient did not improve significantly. This case emphasizes the irreversibility of anti-tubercular therapy-induced peripheral neuropathy, demanding more rigorous clinical screening for the same while managing such patients.

Topics: Adult; Aminosalicylic Acid; Antitubercular Agents; Clofazimine; Cycloserine; Deprescriptions; Diarylquinolines; Ethionamide; Extensively Drug-Resistant Tuberculosis; Female; Humans; Kanamycin; Linezolid; Neural Conduction; Neurotoxicity Syndromes; Peripheral Nervous System Diseases; Pyrazinamide; Pyridoxine; Tuberculosis, Pulmonary

Treatment outcomes of patients with extensively drug-resistant tuberculosis (XDR-TB) are suboptimal and treatment options remain limited. Linezolid is associated with improved outcomes but also substantial toxicity, and details about the relationship between these are lacking from resource-poor HIV-endemic settings.. This was a prospective follow-up study of 63 South African XDR-TB patients (58.7% HIV-infected; median CD4 131 cells/μl) between 2014 and 2018. The frequency and severity of linezolid-associated adverse events and the impact on treatment outcomes were compared between linezolid interrupters and non-interrupters.. Twenty-two patients (34.9%) discontinued or underwent dose reduction due to presumed linezolid-associated toxicity. Anaemia (77.3% vs. 7.3%; p< 0.001), peripheral neuropathy (63.6% vs. 14.6%; p= 0.003), and optic neuritis (18.2% vs. 9.8%; p= 0.34) occurred more frequently in linezolid interrupters than in non-interrupters. Anaemia, peripheral neuropathy, and optic neuritis occurred at a median of 5, 18, and 23 weeks, respectively, after treatment initiation. Linezolid interruption was not associated with unfavourable outcomes but was strongly associated with HIV co-infection (adjusted hazard ratio 4.831, 95% confidence interval 1.526-15.297; p= 0.007) and bacterial load (culture days to positivity; adjusted hazard ratio 0.824, 95% confidence interval 0.732- 0.927; p= 0.001).. Linezolid-related treatment interruption is common, is strongly associated with HIV co-infection, and system-specific toxicity occurs within predictable time frames. These data inform the clinical management of patients with drug-resistant TB.

Topics: Adult; Anemia; Antitubercular Agents; Coinfection; Diarylquinolines; Drug Resistance, Bacterial; Drug Therapy, Combination; Extensively Drug-Resistant Tuberculosis; Female; Fluoroquinolones; Follow-Up Studies; HIV Infections; Humans; Linezolid; Male; Optic Neuritis; Peripheral Nervous System Diseases; Prospective Studies; Treatment Outcome