Publications

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.

Importance

Although strain on hospital capacity has been associated with increased mortality in nonpandemic settings, studies are needed to examine the association between coronavirus disease 2019 (COVID-19) critical care capacity and mortality.

Objective

To examine whether COVID-19 mortality was associated with COVID-19 intensive care unit (ICU) strain.

Design, Setting, and Participants

This cohort study was conducted among veterans with COVID-19, as confirmed by polymerase chain reaction or antigen testing in the laboratory from March through August 2020, cared for at any Department of Veterans Affairs (VA) hospital with 10 or more patients with COVID-19 in the ICU. The follow-up period was through November 2020. Data were analyzed from March to November 2020.

Exposures

Receiving treatment for COVID-19 in the ICU during a period of increased COVID-19 ICU load, with load defined as mean number of patients with COVID-19 in the ICU during the patient's hospital stay divided by the number of ICU beds at that facility, or increased COVID-19 ICU demand, with demand defined as mean number of patients with COVID-19 in the ICU during the patient's stay divided by the maximum number of patients with COVID-19 in the ICU.

Main Outcomes and Measures

All-cause mortality was recorded through 30 days after discharge from the hospital.

Results

Among 8516 patients with COVID-19 admitted to 88 VA hospitals, 8014 (94.1%) were men and mean (SD) age was 67.9 (14.2) years. Mortality varied over time, with 218 of 954 patients (22.9%) dying in March, 399 of 1594 patients (25.0%) dying in April, 143 of 920 patients (15.5%) dying in May, 179 of 1314 patients (13.6%) dying in June, 297 of 2373 patients (12.5%) dying in July, and 174 of 1361 (12.8%) patients dying in August (P < .001). Patients with COVID-19 who were treated in the ICU during periods of increased COVID-19 ICU demand had increased risk of mortality compared with patients treated during periods of low COVID-19 ICU demand (ie, demand of ≤25%); the adjusted hazard ratio for all-cause mortality was 0.99 (95% CI, 0.81-1.22; P = .93) for patients treated when COVID-19 ICU demand was more than 25% to 50%, 1.19 (95% CI, 0.95-1.48; P = .13) when COVID-19 ICU demand was more than 50% to 75%, and 1.94 (95% CI, 1.46-2.59; P < .001) when COVID-19 ICU demand was more than 75% to 100%. No association between COVID-19 ICU demand and mortality was observed for patients with COVID-19 not in the ICU. The association between COVID-19 ICU load and mortality was not consistent over time (ie, early vs late in the pandemic).

Conclusions and Relevance

This cohort study found that although facilities augmented ICU capacity during the pandemic, strains on critical care capacity were associated with increased COVID-19 ICU mortality. Tracking COVID-19 ICU demand may be useful to hospital administrators and health officials as they coordinate COVID-19 admissions across hospitals to optimize outcomes for patients with this illness.