Myth-busting: Azithromycin does not cause torsade de pointes or increase mortality

There are two reasons that azithromycin does not share erythromycin's ability to cause torsade de pointes. First, azithromycin's affinity for cardiac potassium channels is 27 times lower than erythromycin's. Second, azithromycin prolongs the QT interval due to prolongation of the action potential itself, unlike erythromycin which delays repolarization. This could actually give azithromycin anti-arrhythmic properties.

Macrolides: The Plug Is Out

Antibiotics of the macrolide (and streptogramin B) class are unique among the ribosome-targeting antibiotics, as they do not block peptide bond formation in the PTC directly.

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

Macrolides have diverse biological activities and an ability to modulate inflammation and immunity in eukaryotes without affecting homeostatic immunity. These properties have led to their long-term use in treating neutrophil-dominated inflammation in diffuse panbronchiolitis, bronchiectasis, rhinosinusitis, and cystic fibrosis.

The appropriate use of macrolides

Macrolides are effective against gram-positive (excluding enterococci) and some gram-negative bacteria. They are also active against Mycoplasma pneumoniae, Treponema pallidum, Bordetella pertussis, Chlamydia trachomatis, Chlamydophila pneumoniae, Legionella spp., Campylobacter spp. and Borrelia spp.

Adverse events in people taking macrolide antibiotics

People treated with a macrolide antibiotic experienced gastrointestinal adverse events such as nausea, vomiting, abdominal pain, and diarrhoea more often than those treated with placebo.

Antimicrobials and QT prolongation

Despite the long-standing, strong and extensive documentation of antibiotic-associated QT prolongation and resultant life-threatening ventricular arrhythmias,9 this risk seems to be largely ignored by clinicians.

Association of Azithromycin Use With Cardiovascular Mortality

In this cohort study of more than 7.8 million antibiotic exposures, there was a statistically significantly increased relative risk and absolute risk of cardiovascular death associated with azithromycin exposure compared with amoxicillin within 5 days of index date but not within 6 to 10 days after index date.

Does Azithromycin and Cetirizine Combination Given for Upper Respiratory Tract Infections has any Significant Effect on QTc?

During three days treatment with azithromycin and cetirizine, there was significant change in QTc between day 1 and day 4. Patients with baseline QTc greater than 377.5 ms were at risk of QTc prolongation above 430 ms on day 4.

Estimated Cardiac Risk Associated With Macrolides and Fluoroquinolones Decreases Substantially When Adjusting for Patient Characteristics and Comorbidities

Macrolide use is also associated with QT prolongation, and multiple case reports describe cardiac arrhythmias in patients treated with macrolides. However, despite these reports, multiple large retrospective clinical studies investigating the potential risk of the use of macrolides in practice have yielded conflicting results.

Macrolide Antibiotics and the Risk of Cardiac Arrhythmias

Macrolides can prolong the QT and QTc interval and cause cardiac arrhythmias, including TdP, ventricular tachycardia, and ventricular fibrillation, via their effect on the IKr potassium channel. Having conditions associated with QT prolongation or various other comorbidities increases the risk of developing arrhythmias in response to macrolides, perhaps by more than 24-fold.

Macrolide antibiotics and the risk of ventricular arrhythmia in older adults

Among older adults, macrolide antibiotics were not associated with a higher 30-day risk of ventricular arrhythmia than nonmacrolide antibiotics. These findings suggest that current warnings from the US Food and Drug Administration may be overstated.

Macrolide Antibiotics, Prolonged QTc, and Ventricular Dysrhythmias

This study, while not without its limitations, is another piece of evidence that suggests that the risk of ventricular dysrhythmias and death secondary to macrolide antibiotic use may not be as high as once thought. The authors of this study provided a very large sample size, with clinically important outcomes.

Macrolides - Don't Upset the Rhythm

Healthcare professionals should consider the risk of QT prolongation when weighing the risks and benefits of macrolide antibiotics, particularly in at-risk groups.

Macrolides Can Kill

Did you know that the macrolide group of antibiotics (erythromycin and all its cousins) could kill you? Drop dead – sudden death. Well there is a growing body of literature saying just that.

Pharmacokinetics of Macrolide Antibiotics and Transport into the Interstitial Fluid: Comparison among Erythromycin, Clarithromycin, and Azithromycin

Recent research has found higher levels and longer total exposure of azithromycin, a macrolide antibiotic agent, in the interstitial fluid of the skin than in the plasma. This unique distribution is expected to contribute to its antimicrobial activity at the primary infection site.

POTD: QTc Prolongation

Antbiotics – the -ofloxacin’s, Bactrim, macrolides (azithromycin).

So much fear, Roberta, for an antibiotic tablet

It has been known for a long time that some macrolides, such as erythromycin and clarithromycin, can cause proarrhythmic effects – from QT interval prolongation to the appearance of phenomena, sometimes fatal, as polymorphic tachycardia and the more feared “tornades de pointes”. The etiopathogenesis of these phenomena is fundamentally due to two causes: one related to pharmacodynamics and the other one to pharmacokinetics.

Torsades de pointes and QT prolongation Associated with Antibiotics

A new study confirmed the previously-known antibiotics to be associated with Torsades de pointes and QT prolongation (Macrolides, Linezolid, Imipenem and Fluoroquinolones). However, this study found new association between amikacin and Torsades de pointes/QT prolongation.