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What Happened to Z-Packs, the Only Antibiotics I Was Ever Excited to Take?

Like many kids, I was plagued with regular strep throat infections. And, like some kids, my penicillin allergy prevented me from taking the first-line antibiotics to treat those illnesses. So, like many—probably too many—kids and adults, I got Z-Pack antibiotics. Now, decades later, I’m sad to say that basically never happens. Unlike other antibiotics that were usually difficult for me to take as a kid and required multiple doses a day for 10 days or more, Z-Packs only required a breezy five-day course of small, often pink pills. When I got a Z-Pack, I wasn't exactly happy, but I felt like the end to my misery was just a few days away. It was a solution—and I knew relief would come relatively…

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 Azithromycin Use and Risk for Cardiovascular Death

Macrolide antibiotics, as a class, are now known to cause QT prolongation in some at-risk populations Azithromycin, a macrolide, has been associated with cardiovascular death in previous observational studies, although many patients had underlying CVD Although these analyses cannot establish causality, prescribers should be aware of this potential association.

Articles of Interest

Administration of macrolide antibiotics increases cardiovascular risk

The findings of this meta-analysis indicate that macrolide use increases the risk of CVD death, VA or SCD, and myocardial infarction, although not increasing all-cause death. Both azithromycin and clarithromycin increase the incidence of VA or SCD, and azithromycin tends to increase the risk of CVD death and MI. Different CVD risks are increased with different timing of macrolide use.

Association of Azithromycin Use With Cardiovascular Mortality

This cohort study found an approximately 2-fold increased risk of cardiovascular death and noncardiovascular death after outpatient azithromycin use compared with use of amoxicillin within a 5-day window after dispensing. Although these analyses cannot establish causality, prescribers should be aware of this potential association.

Azithromycin Again Linked to Higher CV Mortality Risk

Azithromycin use outside the hospital setting is associated with significantly higher risk of death—both cardiovascular and noncardiovascular—but not sudden cardiac death, according to a retrospective cohort study of data on nearly 3 million people.

Azithromycin tied to higher risk of death

"The benefits of using azithromycin to treat serious infections such as pneumonia are well established and should outweigh the very small possible risk of cardiovascular death in the large majority of cases," said Jonathan Zaroff, MD, a cardiologist at Kaiser Permanente Northern California. "Physicians will need to use their judgment in the rarer situations when the patient has very serious heart disease and there are alternative antibiotics which might be effective in treating the infection."

Azithromycin, cardiovascular risks, QTc interval prolongation, torsade de pointes, and regulatory issues: A narrative review based on the study of case reports

Azithromycin has a broad range of indications and is among the most commonly prescribed macrolide antibiotics in ambulatory care settings]. Safer alternatives may not be available. All macrolides are associated with QTc interval prolongation with risk apparently greater with erythromycin and clarithromycin than with azithromycin

F.D.A. Raises Heart Alert on Antibiotic in Wide Use

Patients at risk for developing this condition include the aging, those with histories of heart problems or with low levels of potassium or magnesium in their blood, those with slow heart rates and those taking medication that is known to lengthen the intervals between heartbeats.

FDA Drug Safety Communication: Azithromycin (Zithromax or Zmax) and the risk of potentially fatal heart rhythms

Health care professionals should consider the risk of fatal heart rhythms with azithromycin when considering treatment options for patients who are already at risk for cardiovascular events...

Should Azithromycin No Longer Be Considered a Drug of Choice for Community-Acquired Pneumonia Because of Its Potential to Cause Cardiovascular Death?

It may be some time before the major societies update their guidelines, but individual institutions and health regions should re-evaluate their CAP guidelines with the goal of removing azithromycin from treatment algorithms, particularly for inpatient use. Hospital inpatients are typically older individuals, often with pre-existing cardiac disease, who are taking multiple medications and are at particular risk for the proarrhythmic effects of azithromycin. If azithromycin is to be used in selected patients, a protocol should be in place to identify how those individuals should be monitored and what degree of QTc prolongation would be tolerated before the drug is discontinued. However, the best approach would be to not use a drug that is not indicated, not effective, and not safe.

The cardiovascular safety of azithromycin

Caution is warranted when prescribing azithromycin to patients with pre-existing QT prolongation or risk factors for it, including hypokalemia, hypomagnesemia and use of other QT-prolonging drugs.

Resources

Azithromycin

Azithromycin is a broad-spectrum macrolide antimicrobial and is among the most prescribed antimicrobial drugs in the United States. It is a derivative of erythromycin with greatly enhanced activity against gram-negative bacteria (including Enterobacteriaceae) and provides coverage of many gram-positive organisms.