Macrolides: What are they? Types, Uses and Risks in Pregnancy

The discovery of telithromycin and its introduction into the market has led to a renewed interest in the chemistry of antibiotics of this type in recent years.

Macrolide antibiotics such as erythromycin, clarithromycin, and azithromycin have been widely used to combat mainly respiratory diseases caused by Gram-positive pathogens and fastidious Gram-negative pathogens.

The popularity of this class of antibiotics is mainly due to its spectrum of activity and its relative safety.

The second-generation macrolides, clarithromycin, and azithromycin are derived from erythromycin and have a broader spectrum of activity and improved pharmacokinetic properties.

Macrolide antibiotics inhibit bacterial protein synthesis by interfering with ribosome function. The details of the inhibitory mechanisms have been clarified by recent advances in the X-ray structure of the ribosome-macrolide complexes.

The widespread use of these antibiotics has catalyzed the appearance of strains resistant to macrolides, especially between Streptococcus pneumonia, Streptococcus pyogenes, and Staphylococcus aureus.

Third-generation macrolides, represented by ketolide telithromycin, are being developed in response to these resistant pathogens.


These derivatives have an increased affinity for the bacterial ribosome and a reduced propensity to be efflux pump substrates compared to the first and second generation macrolides.

As a result, many novel and potent analogs were synthesized and are under investigation. This chapter reviews the main classes of macrolide antibiotics and the newer analogs.

Descriptions of its synthesis, mechanism of action, resistance mechanisms, structure-activity relationship (SAR), pharmacokinetics and safety properties are included.

Macrolide antibiotics include:

  • Azithromycin
  • Clarithromycin.
  • Erythromycin.
  • Spiramycin
  • Telitromicina


  • Sinusitis.
  • Otitis media.
  • Pharyngitis.
  • Tonsillitis.
  • Bronchitis.
  • Infection of skin and soft tissues.

Azithromycin is also used to treat chlamydia, and clarithromycin to eradicate Helicobacter pylori.

The big data for macrolides as a class and erythromycin do not suggest an increase in the overall risk of congenital malformation or cardiac malformations specifically.

There is less data for azithromycin and clarithromycin, and although those available do not suggest an increased risk of congenital malformation, they can not be excluded.

There are risks in pregnancy.

There are no human pregnancy data for telithromycin. The data for spiramycin is insufficient to assess fetal risk with use during pregnancy.

The use of these two macrolides should be reserved for situations in which there are no other therapies for which there is data available on human pregnancy or that are considered clinically appropriate.

Three studies have suggested an increased risk of miscarriage using clarithromycin and one with the help of azithromycin in pregnancy. However, the data for azithromycin are inconsistent, and the possibility of confusion can not be excluded.

The data do not suggest an increased risk of erythromycin, spiramycin, and telithromycin but are extremely limited for the latter two.

The rates of premature births, low birth weight, and neonatal complications did not increase the risk of macrolides as a class or individually when they were studied.

A theoretical risk of pyloric stenosis in the neonate after exposure to macrolides during pregnancy has not been supported by three extensive studies that found no increased rates among the exposed offspring.

Data regarding other neonatal and longer-term outcomes are absent or extremely limited.

Two randomized controlled trials investigating the neurodevelopment of offspring and the risk of cerebral palsy after the use of antibiotics in the management of spontaneous preterm birth or rupture of membranes are contradictory.

Although an electronic study of health records has reported an increased risk of cerebral palsy and epilepsy among children of women treated with macrolides during pregnancy compared to women who received penicillin.

The RCOG discourages the routine use of antibiotics in women in preterm labor without ruptured membranes. Still, treatment with antibiotics should not be stopped at any stage of pregnancy if a pregnant woman shows signs of infection.

A single study has identified an association between asthma and intrauterine exposure to macrolides but found the same for other classes of antibiotics studied and did not consider other reasons for asthma to be more common in these children.

Whenever possible, the results of culture and sensitivity tests should be available before making a treatment decision by local prescription guidelines.

If a macrolide is indicated, erythromycin is the preferred option during pregnancy because there is a more documented experience of its use than other macrolides.

In general, exposure to a macrolide antibiotic at any stage of pregnancy will not be considered medical reasons for the termination of pregnancy or additional control of the fetus.

However, other risk factors may be present in individual cases that may independently increase the risk of an adverse pregnancy outcome.

Physicians are reminded of the importance of taking these factors into account when conducting risk assessments specific to each case.