Impact of Pharmacogenetic Markers on the Safety of Macrolide Therapy in Patients with Bacterial Complications of Influenza
Authors:   Pirogov Russian National Research Medical University, Moscow, Russian Federation, Skryabina A. A. , Nikiforov V. V. ,   Pirogov Russian National Research Medical University, Moscow, Russian Federation, Shakhmardanov M. Z. ,   Pirogov Russian National Research Medical University, Moscow, Russian Federation, Leontieva O. V. ,   Infectious Clinical Hospital No.1, Moscow, Russian Federation, Kostritskaya S. S. ,   Infectious Clinical Hospital No.1, Moscow, Russian Federation, Schetinina T. S. ,   Infectious Clinical Hospital No.1, Moscow, Russian Federation, Sychev D. A. ,   Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation
Published: October 2024

Background. Macrolides are a class of broad-spectrum antibiotics used to treat a variety of infectious diseases, both local and systemic. Although the use of macrolides is generally considered safe, some patients may be at risk of dose-dependent adverse drug reactions (ADRs), which may reduce the safety of treatment for this category of patients. Purpose of the study. To investigate the influence of polymorphism of genes encoding transporter proteins and biotransformation enzymes of macrolide antibiotics on the safety of therapy in patients with bacterial complications of influenza. Material and methods. An open non-comparative prospective study was conducted in which 100 patients diagnosed with bacterial complications of influenza from the lower respiratory tract (ICD-10 diagnosis codes J10.0-J10.1), treated in an infectious disease hospital, received macrolide antibiotics (azithromycin or erythromycin) in tablet form for 5 days. Genotyping was performed by real-time polymerase chain reaction with allele-specific hybridization. Results. The presence of statistically significant influence of the 3435C>T (rs1045642) polymorphic marker of the ABCB1 gene on the frequency of ADRs development in patients treated with macrolides was found: estimation – 0.751, OR = 2.12 (95% CI: 1.03 – 4.34), p = 0.043. In addition, the presence of a statistically significant effect of polymorphic marker C>T intron 6 (rs35599367) of the CYP3A4 gene on the overall incidence of ADRs in patients treated with erythromycin was revealed: estimation – 3.1781, OR = 24.0 (95% CI: 1.2775 – 450.9741), p = 0.0339; and on the incidence of abdominal pain and abdominal discomfort: estimation – 2.0794, OR = 8 (95% CI: 1.0377 – 61.7143), p = 0.046. Discussion: in patients carrying the CT and TT genotypes of the 3435C>T (rs1045642) polymorphic marker of the ABCB1 gene, a higher frequency of such ADRs as abdominal pain and discomfort in the abdomen and diarrhea was observed. Furthermore, the statistically significant influence of the C>T intron 6 (rs35599367) polymorphic marker of the CYP3A4 gene on the frequency of ADRs development against the background of erythromycin use was shown. Conclusion: the influence of ABCB1 genetic polymorphism on the safety parameters of macrolide therapy was demonstrated. It was found that carriage of the C>T intron 6 (rs35599367) polymorphic marker of the CYP3A4 gene may allow to predict the development of ADRs (and specifically abdominal pain) against the background of erythromycin use.