TY - JOUR
T1 - Torsades de pointes and QT prolongation Associations with Antibiotics
T2 - A Pharmacovigilance Study of the FDA Adverse Event Reporting System
AU - Teng, Chengwen
AU - Walter, Elizabeth A.
AU - Gaspar, Daryl Kevin S.
AU - Obodozie-Ofoegbu, Obiageri O.
AU - Frei, Christopher R.
N1 - Funding Information:
No funding was sought for this research study. Dr. Frei was supported, in part, by a NIH Clinical and Translational Science Award (National Center for Advancing Translational Sciences, UL1 TR001120, UL1 TR002645, and TL1 TR002647) while the study was being conducted. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs, the National Institutes of Health, or the authors’ affiliated institutions.
Funding Information:
No funding was sought for this research study. Dr. Frei was supported, in part, by a NIH Clinical and Translational Science Award (National Center for Advancing Translational Sciences, UL1 TR001120, UL1 TR002645, and TL1 TR002647) while the study was being conducted. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs, the National Institutes of Health, or the authors? affiliated institutions.
Publisher Copyright:
© 2019 Ivyspring International Publisher. All rights reserved.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - QT prolongation
KW - Torsades de pointes
KW - adverse drug events
KW - antibiotics
KW - antimicrobial stewardship
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U2 - 10.7150/ijms.34141
DO - 10.7150/ijms.34141
M3 - Article
C2 - 31341415
AN - SCOPUS:85070501153
VL - 16
SP - 1018
EP - 1022
JO - International Journal of Medical Sciences
JF - International Journal of Medical Sciences
SN - 1449-1907
IS - 7
ER -