Safety and Effectiveness of an All-Oral, Bedaquiline-Based, Shorter Treatment Regimen for Rifampicin-Resistant Tuberculosis in High Human Immunodeficiency Virus (HIV) Burden Rural South Africa: A Retrospective Cohort Analysis

Abstract

Background At the end of 2018, South Africa updated its all-oral regimen, to include bedaquiline (BDQ) and two months of linezolid (LZD) for all patients initiating the shorter 9 to 12 months regimen for rifampicin-resistant tuberculosis (RR-TB). We assessed a group of patients in rural KwaZulu-Natal for safety and effectiveness of this treatment regimen under programmatic conditions. Methods We conducted a retrospective cohort analysis on RR-TB patients treated with a standardized all-oral short regimen between July 1, 2018 and April 30, 2019 in three facilities in King Cetshwayo District. An electronic register (EDR Web) and facility-based clinical charts were used to collect variables which were entered into an Epi-Info database. Results Our cohort included 117 patients; 68.4%(95%CI:59.3-76.3) were HIV positive. The median time to culture conversion was 56 days(95%CI:50-57). Treatment success was achieved in 75.2%(95%CI:66.5-82.3) of patients. Mortality within the cohort was 12.8%(95%CI:7.8-20.3). Anaemia was the most frequent severe adverse event. The median time to develop severe anaemia was 7.1 weeks(IQR 4.0-12.9) after treatment initiation. LZD was interrupted in 25.2%(95%CI:17.8-34.5) of participants. Conclusions An all-oral shorter regimen, including BDQ and LZD as core drugs for the treatment of RR-TB, shows good outcomes, in a high HIV burden rural setting. Adverse events (AEs) are common, especially for LZD, but could be managed in the program setting. Support is needed when introducing new regimens to upskill staff in the monitoring, management and reporting of AEs.

Narrative review of the relationship between COVID-19 and PJP: does it represent coinfection or colonization?

“…In critically ill COVID-19 patients who are unable to tolerate diagnostic bronchoscopy, compatible clinical and radiological features with elevated serum biomarkers levels of LDH and BDG may be the only useful tools to warrant an empirical trial of anti-PJP therapy such as sulfamethoxazole-trimethoprim (SMX-TMP) [ 59 ]. BDG levels are typically low, less than the cut-off of 80 pg/mL in COVID-19 infection, as the COVID-19 virus lacks the polysaccharide cell walls present in certain fungal and bacteria microorganisms [ 60 , 61 ]. In 2011, a meta-analysis demonstrated that serum BDG had 94.8% sensitivity and 86.3% specificity for the diagnosis of PJP in the setting of compatible clinical manifestations and risk factors [ 62 ].…”

Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis

“…The odds of death within 30 days of ICU admission increased 1.41-fold (1.10–1.81; p = 0.007) for each point increase in the initial BAL GM index [ 19 ]. In the study of White et al, all-cause mortality rates ranged from 46.7% (95% CI 24.8–69.9) in CAPA patients receiving appropriate antifungal therapy to 100% (95% CI 51.1–100) in patients not receiving appropriate antifungal therapy [ 20 ]. Van Biesen et al found a mortality of 22.2% in patients with CAPA based on NBL and 15.1% in patients without CAPA [ 42 ].…”

Treatment outcomes 24 months after initiating short, all-oral bedaquiline-containing or injectable-containing rifampicin-resistant tuberculosis treatment regimens in South Africa: a retrospective cohort study

“…This finding is consistent with a meta-analysis 22 that established that the use of injectable agents was associated with higher mortality among patients with rifampicin-resistant tuberculosis and other meta-analyses 22 , 23 that suggested bedaquiline has the potential to achieve a higher sputum culture conversion rate and a lower mortality risk among patients with rifampicin-resistant tuberculosis compared with patients not receiving bedaquiline. A study by Tack and colleagues 24 suggests an all-oral, bedaquiline-based regimen that includes linezolid is safe and effective; however, the study was not comparative and it remains to be elucidated if such a regimen would be superior to the bedaquiline-containing regimen (without linezolid) in this analysis.…”