Chloroquine-induced QTc prolongation in COVID-19 patients.

BACKGROUND: In the battle against the SARS-CoV­2 pandemic, chloroquine has emerged as a new potential therapeutic option for the treatment of infected patients. A safety consideration for the application of chloroquine is its QTc-prolonging potential. Thus far, no data are available on the QTc-prolonging potential of chloroquine in COVID-19 patients. OBJECTIVE: To assess the degree of chloroquine-induced QTc prolongation in hospitalised COVID-19 patients. METHODS: A baseline electrocardiogram (ECG) and ECGs recorded during chloroquine treatment were retrospectively collected in patients suspected of having COVID-19. The QTc interval was calculated by computerised and manual interpretation. Baseline and follow-up QTc intervals were compared using the paired samples t-test. RESULTS: A total of 95 patients had a baseline ECG recording and at least one ECG recording during chloroquine therapy. Chloroquine treatment resulted in a mean QTc prolongation of 35 ms (95% CI 28-43 ms) using computerised interpretation and 34 ms (95% CI 25-43 ms) using manual interpretation. No torsade de pointes was observed during chloroquine treatment. After manual review, 22 patients (23%) had a QTc interval exceeding 500 ms during chloroquine treatment. None of these patients had a prolonged QTc interval prior to the initiation of chloroquine treatment. CONCLUSIONS: Chloroquine significantly prolongs the QTc interval in a clinically relevant matter. This highlights the need for ECG monitoring when prescribing chloroquine to COVID-19 patients.

Monitoring of tobramycin serum concentrations in selected critically ill patients receiving selective decontamination of the digestive tract: a retrospective evaluation.

INTRODUCTION: Selective decontamination of the digestive tract (SDD) is a strategy in mechanically ventilated patients to reduce mortality. Treatment consists of enterally administered non-absorbable antibiotics, i.e., tobramycin. However, most intensive care unit (ICU) patients with SDD appear to have detectable tobramycin serum concentrations. The Rijnstate Hospital implemented a protocol for therapeutic drug monitoring (TDM) of tobramycin in patients at risk. The aim of this study was to evaluate the necessity of TDM in these patients and to optimize the current protocol. METHODS: This retrospective observational study included ICU patients with SDD treatment for ≥ 7 days and renal failure. These patients were considered eligible for monitoring of tobramycin. Tobramycin serum concentrations, relevant laboratory parameters (i.e., renal function, lactate), and patient data were extracted from the National Intensive Care Evaluation database and the hospital electronic patient data system. RESULTS: In 23 subjects, a total of 43 tobramycin serum concentrations was determined. The median tobramycin serum concentration was 0.33 (IQR 0.17-0.49) mg/L of which 12 (27.9%) samples had concentrations < 0.2 mg/L, 30 (69.8%) had concentrations 0.2-1.0 mg/L and 1 (2.3%) had a toxic concentration > 1.0 mg/L. In 3 (7.0%) cases, an intervention was conducted based on the tobramycin serum concentration. CONCLUSION: The majority (83.7%) of samples had detectable tobramycin serum concentrations. Monitoring of tobramycin serum concentrations can be considered necessary in patients at risk. However, the current protocol should be optimized to intercept patients more precise.

The long-term safety of chronic azithromycin use in adult patients with cystic fibrosis, evaluating biomarkers for renal function, hepatic function and electrical properties of the heart.

Background: Azithromycin maintenance therapy is widely used in cystic fibrosis (CF), but little is known about its long-term safety. We investigated whether chronic azithromycin use is safe regarding renal function, hepatic cell toxicity and QTc-interval prolongation.Methods: Adult CF patients (72 patients using azithromycin for a cumulative period of 364.8 years and 19 controls, 108.8 years) from two CF-centers in the Netherlands with azithromycin (non)-use for at least three uninterrupted years were studied retrospectively.Results: There was no difference in mean decline of estimated glomerular filtration rate (eGFR), nor in occurrence of eGFR-events. No drug-induced liver injury could be attributed to azithromycin. Of the 39 azithromycin users of whom an ECG was available, 4/39 (10.3%) had borderline and 4/39 (10.3%) prolonged QTc-intervals, with 7/8 patients using other QTc-prolonging medication. Of the control patients 1/6 (16.7%) had a borderline QTc-interval, without using other QTc-prolonging medication. No cardiac arrhythmias were observed.Conclusion: We observed no renal or hepatic toxicity, nor cardiac arrythmias during azithromycin use in CF patients for a mean study duration of more than 5 years. One should be aware of possible QTc-interval prolongation, in particular in patients using other QTc-interval prolonging medication.