Continuing Education Activity

Macrolides are a class of drugs used in the management and treatment of various bacterial infections. This activity reviews the mechanism of action, indications, contraindications, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) related to macrolides.


  • Identify the mechanism of action of the macrolide class of antibiotics.
  • Describe the adverse effects and contraindications of the macrolide class of antibiotics.
  • Review the appropriate monitoring and toxicity of the macrolide class of antibiotics.
  • Describe interprofessional team strategies for improving the proper administration and management of macrolide antibiotics.


The FDA has approved the use of macrolide antibiotics for a wide variety of bacterial infections. Azithromycin, clarithromycin, and erythromycin, in particular, are used commonly to treat infections like pneumonia, sinusitis, as well as pharyngitis and tonsillitis. Also, the FDA has approved its use in uncomplicated skin infections and otitis media in pediatric patients. Moreover, clarithromycin, in particular, is used to treat Helicobacter pylori infections in standard triple therapy protocol regardless of clarithromycin resistance status. Macrolides are also commonly used to treat sexually transmitted infections such as gonococcal and chlamydial infections. The majority of macrolide use, like other antibiotics, is dictated by susceptibility and resistance status of the targetted organism.[1][2][3] Macrolides have also been one of the primary drugs used to treat atypical pneumonia, usually caused by organisms like Mycoplasma pneumoniae, Legionella, as well as Chlamydia pneumoniae.[4]

In recent studies, macrolide maintenance therapy has been shown to improve quality of life and spirometry findings in adults and children with non-cystic fibrosis bronchiectasis. Further, these agents have been shown to reduce the number of bronchiectasis exacerbations. However, these studies revealed no reduction in hospital admissions pertaining to exacerbations.[5]

Macrolides remain an integral part of treatment regimens for COPD exacerbations. The use of these drugs in COPD is because of their anti-inflammatory and immunomodulating characteristics.[6]

Mechanism of Action

The mechanism of action of macrolides revolves around their ability to bind the bacterial 50S ribosomal subunit causing the cessation of bacterial protein synthesis. Once bound, the drug prevents the translation of mRNA, specifically the growing peptide chain, by preventing the addition of the next amino acid by the tRNA. Since the bacterial ribosomal structure is highly conserved across most, if not all, bacterial species, it is considered to be broad-spectrum.[7] Macrolides are considered to be bacteriostatic as they only inhibit protein synthesis, although, at high doses, they can be bactericidal.

The anti-inflammatory and immunomodulatory effects of macrolides, particularly azithromycin, are attributed to interactions with phospholipids as well as transcription factors AP-1, NF-kappaB, and other inflammatory cytokines. Later changes seen in macrophages that interact with macrolides include inhibition of cell function and cellular transport along with surface receptor expression regulation. All of these culminate in the immunomodulatory effects of macrolides in the body.[1]

Due to the overprescription of antibiotics, there has been tremendous growth in resistance to many mainstay therapies. Macrolides are no exception to this, and many organisms are excessively resistant to them. Studies show a strong link to genetic mutations in bacteria and the ability to spread these genes via transposable elements. The gene in question allows bacteria to be resistant to macrolides as well as lincosamides, and streptogramin groups of antibiotics at once.[8]


The formulation of the drug requires discussion with the administering provider. The factors that one needs to take into account are strength, dosage, route, clinical goals of treatment, etc. Macrolides come in various forms for administration, depending on the desired medication and reason for their use. Most commonly used are oral formulations in tablet form, but they also come as topical creams, intravenous formulations, as well as ophthalmic preparations.

The following list includes the most common macrolides and their most common formulations, however, other formulations and dosages do exist[3]:

  • Erythromycin
    • 250mg / 500mg – oral tablets
  • Clarithromycin
    • 125mg / 250mg / 500mg / 1000mg (extended release) – oral tablets
  • Azithromycin
    • 100mg / 250mg / 500mg / 600mg – oral tablets

Adverse Effects

Like any other antibiotic, macrolides carry a significant risk of the typical adverse effects like nausea, vomiting, abdominal pain, as well as diarrhea. Abdominal symptoms are largely the result of macrolides being motilin agonists causing an increased risk of gastrointestinal upset and side effects.[9] Besides, the enteric gut flora is susceptible to the effects of macrolides; therefore, it can cause an imbalance between commensal bacteria native to the human gut and pathogenic bacteria to be kept in check.

Another common, but serious adverse effect associated with macrolides use, is their propensity to prolong the QT and QTc interval in the cardiac cycle. Erythromycin has the highest tendency, and azithromycin has the lowest. The increase in the intervals puts patients at risk of cardiac arrhythmias like Torsades de pointes, ventricular tachycardia, and ventricular fibrillation. The most common arrhythmia arising from the use of macrolides would be Torsades de Pointes.[10]  

Recent studies on macrolides have also shown that the use of these drugs correlates with sensorineural hearing loss. While the majority of cases were reversible with cessation of the drug, few cases resulted in irreversible sensorineural hearing loss. Studies have shown that hearing loss can occur both at standard doses and increased doses.[11] 

Serious side effects like Stevens-Johnsons syndrome and toxic epidermal necrolysis, although rare, are a possibility and should be kept in mind while prescribing these drugs.[12]  

Erythromycin also has correlations with hepatotoxicity in pregnant women. Moreover, these drugs increase the chances of pyloric stenosis in newborns.[3]


Overall, macrolides are a safe group of antibiotics to take, but relative contraindications exist due to the adverse effects profile and their ability to interact with other drugs. Primarily, patients with prolonged QT intervals on electrocardiograms should avoid macrolides due to their arrhythmogenic characteristics. Further, patients with congenital conditions like long QT syndrome type 2 should also avoid these drugs. Patients taking Class Ia and Class III antiarrhythmic agents should also avoid macrolides as both of these drug classes cause an increase in QT interval and induce arrhythmias.

Pregnant women should also try to avoid the use of macrolides, specifically erythromycin, due to possible side effects to the mother or the newborn.

Due to the increasing rate of antibiotic resistance, macrolides should be prescribed with caution, and the prescriber should take into account the local resistance status of common pathogens.


When prescribing macrolides, the prescriber should consider the variety of gastrointestinal side effects as well as cardiac effects that the patient could encounter with macrolide use. In most patients, gastrointestinal side effects will be the most common, and the team should be ready to take proper measures to counter these effects. Due to the risk of QT prolongation, careful monitoring of patients, with cardiac conditions as well as those taking antiarrhythmics or drugs known to cause interaction, should be carried out. Prescribers should also be aware of possible dermatologic side effects and thus should counsel patients on the side effects. Concerning possible side effects in pregnant women and newborns, patients require counsel on the adverse effects of these drugs in pregnancy, as well as the probable adverse impact on the newborn when prescribing these drugs.


Due to the severity of the cardiac side effects, monitoring of the QT interval on ECG should be done in high-risk patients to avoid the induction of deadly arrhythmias like Torsades de Pointes. Patients that are at high risk should have electrolytes checked before administration of the medications, specifically calcium, potassium, and magnesium.[3] Cessation of the drug is necessary if serious side effects arise in a patient. If possible, another antibiotic should be used over macrolides in these high-risk patients to avoid the chance of inducing arrhythmias.

Enhancing Healthcare Team Outcomes

Although macrolides are a very safe class of antibiotics, proper healthcare administration by the entire team should be done to minimize adverse events. All members of the interprofessional healthcare team should monitor patients for the common side effects as well as the uncommon ones. All members need education regarding common gastrointestinal side effects as well as the serious cardiac effects this drug has. Every member of the healthcare team shares in the responsibility of providing top-notch care to their patients and should always be on the lookout for potential side effects.

When deciding to initiate macrolide therapy, the clinician would do well to include a pharmaceutical consult, which would consist of verifying the appropriateness of the agent chosen, verification of proper dosing, and checking for drug-drug interactions. Nursing can provide monitoring and also answer patient questions about their therapy, and report on treatment progress or lack thereof, or the presence of adverse effects. All members of the healthcare team should know the most common uses of the macrolide class of antibiotics and exercise collaborative efforts to ensure optimal patient outcomes. [Level 5]

Article Details

Article Author

Parth Patel

Article Editor:

Muhammad Hashmi


2/11/2021 12:09:01 AM

PubMed Link:




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