RESUMO
Background: Linezolid has been prioritized for treating multidrug-resistant tuberculosis (MDR TB), but toxicity limits its use. We report treatment outcomes for MDR TB patients in California who received standard-dose linezolid vs those who switched to low-dose. Methods: We include culture-positive MDR TB cases treated with linezolid and receiving California MDR TB Service consultation during 2009-2016. Demographic, clinical, and laboratory data are analyzed using univariate analysis to compare patients who received linezolid of different dosing strategies. Analysis end points are linezolid treatment duration (measure of tolerability), treatment success (completion or cure), and adverse events (AEs). Results: Sixty-nine of 194 (36%) MDR TB patients met inclusion criteria. While all patients began linezolid treatment at 600â mg daily, 39 (57%) continued at this dosage (standard-dose), and 30 (43%) switched to 300â mg daily (29%) or intermittent dosing (14%) (low dose). Patients on standard-dose linezolid were treated for 240 days, compared with 535 for those on low-dose (P < .0001). Sixty-three patients (91%) achieved treatment success, 2 (2.9%) died, 1 (1.5%) failed treatment, 1 (1.5%) stopped treatment due to side effects, and 2 (2.9%) were lost or moved. Treatment success was higher (P = .03) in the low-dose group. Sixty-two patients experienced ≥1 hematologic (71%) or neurologic (65%) AE. Those on low-dose linezolid experienced significantly (P = .03) fewer AEs per linezolid-month after switching (0.32 vs 0.10). Conclusions: Patients who switched to low dose tolerated linezolid longer with better treatment outcomes and fewer recurring AEs.
RESUMO
BACKGROUND: Bedaquiline (BDQ) is recommended for the treatment of multidrug-resistant tuberculosis (MDR TB), however, it has the potential to prolong QTc interval. We assessed the frequency and severity of QTc prolongation in patients receiving BDQ in California. METHODS: Based on chart review for patients receiving BDQ as part of MDR TB therapy from January 2013-May 2019, we analyzed QTc values at six pre-specified time points during BDQ therapy (baseline, 2, 4, 8, 12, and 24 weeks), as well as peak QTc, time to peak QTc, and the clinical characteristics of patients who had QTc elevation >500 milliseconds (ms) during therapy. RESULTS: A total of 37 patients were treated with BDQ during the analysis period, with a total of 449 QTc measurements available for analysis. Most patients (89%) received at least one QTc-prolonging drug in addition to BDQ. Median QTc values at all pre-specified time points were <450 ms. Median peak QTc was 455 ms (interquartile range [IQR]: 437-486) and median time to peak was 57 days (IQR: 19-156). Four patients (11%) had a non-transient elevation in QTc to >500 ms, including one patient with profound hypokalemia and one receiving concurrent chemotherapy, but none had cardiac arrhythmia. Less than 10% of patient in our cohort had ECGs performed at all six pre-specified time points. DISCUSSION: BDQ was generally well-tolerated in a cohort of patients treated for MDR TB in California, with 11% of patients experiencing a non-transient QTc elevation >500 ms, and no episodes of arrhythmia. Frequent ECG monitoring during BDQ therapy presents a challenge for TB clinicians, even in well-resourced countries.
