Do Vancomycin or Piperacillin/Tazobactam prolong the QT interval?

Vancomycin and Piperacillin/Tazobactam Do Not Prolong the QT Interval

Neither vancomycin nor piperacillin/tazobactam (Zosyn) are known to cause QT interval prolongation, and both can be safely used in patients with risk factors for QT prolongation or pre-existing QTc prolongation. 1

Vancomycin Safety Profile

• Vancomycin is notably absent from all major cardiac society lists of QT-prolonging medications, including comprehensive reviews by the American College of Cardiology, American Heart Association, and Heart Rhythm Society 2, 1

• Vancomycin represents a safe option from an electrophysiological standpoint for patients with multiple risk factors for QT prolongation, including age >65 years, hypokalemia, hypomagnesemia, heart failure, or concomitant use of other QT-prolonging medications 1

• The American College of Cardiology specifically recommends that vancomycin can be used safely in patients with risk of QT prolongation or those with already prolonged QTc, unlike macrolides and fluoroquinolones which require careful cardiac monitoring 1

Piperacillin/Tazobactam (Zosyn) Safety Profile

• Piperacillin/tazobactam does not appear on guideline lists of QT-prolonging antibiotics from the American College of Cardiology, American Heart Association, or European Society of Cardiology 2, 1

• One multicenter observational study found an association between piperacillin/tazobactam and QTc prolongation at univariate analysis, but this association did not remain significant after multivariate adjustment for confounding factors 3

• The lack of biological plausibility is important: piperacillin/tazobactam does not block the hERG potassium channels (IKr current) that are responsible for drug-induced QT prolongation, unlike macrolides, fluoroquinolones, and other known culprit antibiotics 2, 1

Antibiotics That DO Prolong QT Interval

For context, the following antibiotics are definitively associated with QT prolongation and should be avoided or used with caution in at-risk patients:

High-Risk Antibiotics

• Macrolides: Erythromycin (especially IV), azithromycin, and clarithromycin all block cardiac potassium channels and cause QT prolongation 2, 1

  • Intravenous erythromycin carries the highest risk of torsades de pointes among macrolides 1
  • Azithromycin is recognized as a definite cause of torsades de pointes by the American College of Cardiology, though with lower absolute risk than erythromycin 1, 4

• Fluoroquinolones: Moxifloxacin carries the greatest risk, followed by levofloxacin; ciprofloxacin has the lowest risk 1, 5

• Trimethoprim: Listed by the European Heart Journal as causing QT prolongation through IKr blockade 2, 1

Clinical Implications

• No baseline ECG or QTc monitoring is required when prescribing vancomycin or piperacillin/tazobactam solely based on cardiac safety concerns 1

• These agents can be used as preferred alternatives when treating infections in patients with prolonged QTc (≥500 ms), congenital long QT syndrome, or multiple risk factors for torsades de pointes 1

• Common pitfall to avoid: Do not confuse beta-lactam/beta-lactamase inhibitor combinations with macrolides or fluoroquinolones when assessing cardiac risk 1, 3