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Rapid Molecular Detection and Differentiation of Influenza Viruses A and B
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Pharmacogenetic markers and macrolide safety in influenza patients: insights from a prospective study

A A Skryabina1, V V Nikiforov1, M Z Shakhmardanov1

  • 1Infectious Diseases Department, Pirogov Russian National Research Medical University, Moscow, Russia.

Pharmacogenomics
|January 20, 2025
PubMed
Abstract

Insights

Genetic variations in ABCB1 and CYP3A4 influence macrolide antibiotic safety. Pharmacogenetic testing may reduce adverse drug reactions in susceptible patients, improving antibiotic safety.

Area of Science:

  • Pharmacogenetics
  • Infectious Diseases
  • Clinical Pharmacology

Background:

  • Macrolide antibiotics are frequently prescribed but can cause adverse drug reactions (ADRs).
  • Genetic predisposition significantly impacts individual susceptibility to macrolide-induced ADRs.
  • Influenza complications provide a relevant clinical context for studying antibiotic safety.

Purpose of the Study:

  • To investigate the association between specific gene polymorphisms and the risk of ADRs.
  • To evaluate the role of transporter (ABCB1) and enzyme (CYP3A4, CYP3A5) gene variants in macrolide therapy safety.
  • To determine if pharmacogenetic markers can predict macrolide-related adverse events in patients with bacterial influenza complications.

Main Methods:

  • Prospective study of 100 participants with bacterial influenza complications.
  • Treatment with azithromycin or erythromycin for five days.
  • Genotyping for ABCB1 (3435C>T), CYP3A4 (C>T intron 6), and CYP3A5 (6986A>G) polymorphisms; daily ADR monitoring and correlation with genetic data.

Main Results:

  • The ABCB1 (3435C>T) polymorphism correlated with increased abdominal pain and diarrhea (OR=2.12, p=0.043).
  • CYP3A4 (C>T intron 6) polymorphism significantly elevated ADR risk with erythromycin (OR=24.0, p=0.0339).
  • No significant association was found for CYP3A5 (6986A>G) polymorphism with ADRs.

Conclusions:

  • Genetic variations in ABCB1 and CYP3A4 are predictive of macrolide-related adverse drug reactions.
  • Pharmacogenetic screening can enhance macrolide safety, especially in genetically susceptible individuals.
  • Personalized antibiotic therapy guided by pharmacogenetics may mitigate risks associated with macrolide use.
Keywords:
ABCB1CYP3A4Pharmacogeneticsadverse drug reactionsazithromycinmacrolidespersonalized medicine

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