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Key messages
Macrolides target protein synthesis at the bacterial ribosomes and exert immunomodulatory effects. They usually cover Gram-positive and Gram-negative aerobic bacteria, and atypical bacteria.
The different macrolides demonstrate varying pharmacokinetic profiles, which is an important factor to consider when prescribing, as it results in different dosing schedules, interactions and side effects.
Long-term prophylactic azithromycin likely reduces the exacerbation frequency of children with bronchiectasis, and might improve the lung function. However, prolonged use increases antimicrobial resistance. Therefore, it is imminent to review prophylactic indications regularly.
Introduction
Erythromycin was the first macrolide, a group of antibiotics that share a macrocyclic ring at a molecular level. Clarithromycin and azithromycin are newer agents of this group, and are among the most frequently prescribed antibiotics for children.1 Beyond antibacterial effects, macrolides exert immunomodulatory actions. Macrolides are increasingly prescribed for prophylactic indications. Furthermore, owing to its prokinetic action, erythromycin is sometimes prescribed to increase gastric emptying. In this medicines update, we provide the reader with a pharmacological background to prescribe macrolides judiciously.
Mode of action
Macrolides inhibit protein synthesis through binding at the 50 s subunit of bacterial ribosomes.2 Translation, the process of protein synthesis from mRNA, is inhibited after attachment to this subunit, so that it impedes further bacterial growth. Hence, the antibacterial effect of macrolides is usually bacteriostatic. Furthermore, macrolides decrease neutrophil count and function, resulting in lower concentrations of neutrophil elastase, interleukin 8, and tumour necrosis factor alpha.3 To a lesser extent, macrolides have been reported to reduce the function of eosinophils and T-helper 2 cells. However, mechanisms responsible for these effects are not fully understood, and data comparing these effects between different macrolides are scarce.
Pharmacokinetics
Macrolides are time-dependent antibiotics, meaning that their antibacterial effect is determined by the time above the minimum inhibitory curve, which is governed by the pharmacokinetic processes absorption, distribution, metabolism and …
Footnotes
Contributors Both authors contributed equally.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; externally peer reviewed.