Int J Med Sci 2019; 16(7):1018-1022. doi:10.7150/ijms.34141
Torsades de pointes and QT prolongation Associations with Antibiotics: A Pharmacovigilance Study of the FDA Adverse Event Reporting System
1. Pharmacotherapy Division, College of Pharmacy, The University of Texas at Austin, San Antonio, TX, USA
2. Pharmacotherapy Education and Research Center, Long School of Medicine, University of Texas Health-San Antonio, San Antonio, TX, USA
3. Division of Infectious Diseases, Long School of Medicine, University of Texas Health-San Antonio, San Antonio, TX, USA
4. South Texas Veterans Health Care System, San Antonio, TX, USA
5. University Health System, San Antonio, TX, USA
Introduction: Macrolides, linezolid, imipenem-cilastatin, fluoroquinolones, penicillin combinations, and ceftriaxone are known to be associated with Torsades de pointes/QT prolongation (TdP/QTP). Other antibiotics may also lead to TdP/QTP, but no study has systemically compared TdP/QTP associations for many available antibiotics.
Objectives: The objective of this study was to evaluate the association between TdP/QTP and many available antibiotics using the FDA Adverse Event Report System (FAERS).
Methods: FAERS reports from January 1, 2015 to December 31, 2017 were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify TdP/QTP cases. We calculated the Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95%CI) for the association between antibiotics and TdP/QTP. An association was considered to be statistically significant when the lower limit of the 95%CI was greater than 1.0.
Results: A total of 2,042,801 reports (including 3,960 TdP/QTP reports) were considered, after inclusion criteria were applied. Macrolides had the greatest proportion of TdP/QTP reports. Of the 4,092 reports associated with macrolides, 108 reports (2.6%) were associated with TdP/QTP. Significant TdP/QTP RORs (95%CI) for the antibiotics were (in descending order): macrolides 14.32 (11.80-17.38), linezolid 12.41 (8.52-18.08), amikacin 11.80 (5.57-24.97), imipenem-cilastatin 6.61 (3.13-13.94), fluoroquinolones 5.68 (4.78-6.76), penicillin combinations 3.42 (2.35-4.96), and ceftriaxone 2.55 (1.41-4.62).
Conclusion: This study confirms prior evidence for TdP/QTP associations with macrolides, linezolid, imipenem-cilastatin, fluoroquinolones, penicillin combinations, and ceftriaxone. This study also identifies a new association between amikacin and TdP/QTP.
Keywords: Torsades de pointes, QT prolongation, adverse drug events, antibiotics, antimicrobial stewardship
Teng C, Walter EA, Gaspar DKS, Obodozie-Ofoegbu OO, Frei CR. Torsades de pointes and QT prolongation Associations with Antibiotics: A Pharmacovigilance Study of the FDA Adverse Event Reporting System. Int J Med Sci 2019; 16(7):1018-1022. doi:10.7150/ijms.34141. Available from http://www.medsci.org/v16p1018.htm