1322 - Quantifying the Effects of Frequently Prescribed Antimicrobials with Perceived Potential for QT Interval Prolongation during the COVID-19 Era

Background: Countless diseases and medications have been implicated in the past as causing prolongation of the QT interval. Their unique role through the means of quantifying the definite magnitude of relative risk they contribute during hospitalization still requires further investigation. The aim of this study was to describe the impact of commonly used anti-infectives on the QT interval in hospitalized patients during the COVID-19 era.

Methods: Demographic information, medical history, laboratory data, medication administration history and ECG recording data was collected from the electronic records of adult patients admitted to two urban hospitals. A mixed effects approach with four sub-models for the QT interval comprised of: heart rate, circadian rhythm, gender, and the drug (regressed as the cumulative mg dose administered over time) and disease effects was used. Fixed and random effects with between occasion variability were estimated for the parameters with a Bayesian approach using the STAN software.

Results: Data from 2180 patients were used with baseline characteristics shown in Table 1. Observed vs. predicted plots based on the training (Figure 1.A) and validation data set (Figure 1.B) showed excellent fit. The parameters for QT_c0, α, gender, and circadian rhythm were identified within the range previously described (Table 2.). Similarly, the model correctly identified the impact of acute or chronic diseases on the QT interval. Model coefficient estimates [mean (95% CI) of 0.010 (0.006, 0.15) and 0.0045 (0.0013, 0.01100) msec/mg cumulative dose, respectively] suggest that patients treated with conventional regimens of fluconazole and levofloxacin are most likely to present with a QT interval increase > 5 msec, the cutoff threshold of regulatory concern.Figure 1. A-B
Table 1.
Table 2.


Conclusion: The model developed accurately identified the impact baseline risk factors and concomitant medications have on the QT interval. When adjusted for these confounding variables, estimates of QT interval prolongation show that treatment with fluconazole and levofloxacin pose a considerable risk; while treatment with azithromycin or hydroxychloroquine is of moderate risk for QT interval prolongation.