What is the clinical evidence from this study?

Study design: Observational. Population: Torsades de pointes and QT prolongation (n=2042801). Intervention: Macrolides vs. All other drugs in FAERS. Primary outcome: Torsades de pointes/QT prolongation (TdP/QTP) (ROR 14.32, 95% CI 11.80-17.38).

January 1, 2019International Journal of Medical Sciences48 citationsOpen Access

Torsades de pointes and QT prolongation Associations with Antibiotics: A Pharmacovigilance Study of the FDA Adverse Event Reporting System

CTChengwen Teng EWElizabeth Walter DGDaryl Kevin S. Gaspar

Key Result

Macrolides had the strongest association with Torsades de pointes and QT prolongation among evaluated antibiotics, demonstrating a reporting odds ratio of 14.32.

Study Design

Type

Observational (n=2,042,801)

Structured PICO

Do specific antibiotics increase the reporting odds of Torsades de pointes and QT prolongation?

Population

2,042,801 adverse event reports from the FDA Adverse Event Report System (FAERS) between January 1, 2015 and December 31, 2017

Intervention

Various antibiotics including macrolides, linezolid, amikacin, imipenem-cilastatin, fluoroquinolones, penicillin combinations, and ceftriaxone

Comparator

Other adverse event reports in the FAERS database

Outcome

Torsades de pointes/QT prolongation (TdP/QTP) identified using the Medical Dictionary for Regulatory Activities (MedDRA)safety

Pharmacovigilance data confirms that macrolides, linezolid, and amikacin have the highest reporting odds for Torsades de pointes and QT prolongation among antibiotics.

Main Result

Effect estimate: ROR 14.32 (95% CI 11.80-17.38)

Limitations

A causal relationship between a drug and an ADR cannot be determined by FAERS.
Significant bias may occur because of the spontaneous and voluntary reporting of ADRs.
The association between a drug and an ADR is confounded by comorbid diseases and concomitant drugs.

Abstract

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).

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