Macrolides – mechanisms of action, clinical use and antimicrobial resistance

Introduction. Macrolides are a class of antibiotics with a broad spectrum of activity and primarily bacteriostatic effects. They are commonly used in the treatment of respiratory tract infections, skin infections and genital infections, as well as recurrent infections associated with chronic inflammation. However, the emergence of bacterial resistance to macrolide antibiotics highlights the need for in-depth research, including at the genomic level, to better understand their mechanisms of action. A detailed understanding of these mechanisms enables the development of more effective chemotherapeutic agents and the formulation of innovative therapeutic strategies. Materials and method. A systematic review of the literature was conducted using databases such as PubMed Central, Cochrane Library, MEDLINE, HINARI and Google Scholar. A total of 42 sources from the period 2000-2025 were analyzed. The selected studies were chosen based on relevance and scientific quality, with a special focus on the mechanisms of action described in the context of the targeted conditions. Results and discussion. According to the literature, macrolides act by inhibiting bacterial protein synthesis, particularly by blocking the formation of the polypeptide chain. This is achieved by narrowing the nascent peptide exit tunnel (NPET). In the case of short peptides, macrolides block the ribosome through direct interaction. Research also shows that protein synthesis is influenced both by the timing of the interaction between the nascent peptide and the macrolide located in the NPET and by the specific codon sequence being translated at that time. The development of antimicrobial resistance to macrolides involves several mechanisms, including: structural modification of the binding site; efflux of macrolides from the bacterial cell; enzymatic modifications of the antibiotic molecule; and alterations in the peptidyl transferase center and the exit tunnel of the nascent protein. Understanding the mechanisms underlying resistance can support the optimization of macrolide-based therapies and the development of new, more effective antimicrobial agents. Conclusions. Macrolides inhibit bacterial protein synthesis, but are increasingly subject to microbial resistance. A thorough understanding of both their mechanisms of action and resistance is essential for optimizing current treatments and developing new, more effective therapeutic options.