INHIBITORII DE BETA-LACTAMAZE - O CALE EFICIENTĂ DE COMBATERE A REZISTENŢEI LA ANTIBIOTICE

Abstract

Introducere. Creşterea rezistenţei microbilor la antibiotice constituie o problemă de sănătate publică. Una din cauzele majore ale rezistenţei la beta-lactamine s-a raportat a fi producerea de beta-lactamaze. Pentru combaterea inactivării beta-lactaminelor prin beta-lactamaze s-au elaborat inhibitori de beta-lactamaze. Scopul studiului a constat în analiza şi sistematizarea proprietăţilor şi mecanismelor de acţiune ale inhibitorilor de beta-lactamaze pentru argumentarea perspectivelor de combatere a rezistenţei. Material şi metode. A fost realizată o selectare a articolelor publicate în perioada 2018-2025 din bazele de date PubMed, urmată de analiza şi sistematizarea ulterioară a datelor referitor la structura, proprietăţile şi mecanismele de acţiune prin utilizarea cuvintelor cheie: antibiotice beta-lactamice, beta-lactamaze, mecanism de acţiune, rezistenţă. Rezultate. S-a raportat că microorganismele produc patru clase de beta-lactamaze: A, B, C şi D. Clasa B este metalo-beta-lactamaza, în timp ce restul sunt serin beta-lactamaze. În baza studiului structurii beta-lac-tamazelor s-au elaborate: a) inhibitori de beta-lactamaze cu structură beta-lactamică: acidul clavulanic, sulbactam, tazobactam, avibactam, relebactam, vaborbactam, tanibor-bactam, vaborbactam, xeruborbactam, zidebactam; b) inhibitori de beta-lactamaze de structură non-beta-lactamică: durlobactam, enmetazobactam, relebactam, nacubactam. Utilizarea clinică a inhibitorilor de beta-lactamază a permis combaterea rezistenţei la beta-lactamine. Concluzii. Elaborarea inhibitorilor de beta-lactamaze a permis obţinerea antibacterienelor combinate: tazobactam+piperacilină; avibactam+ceftazidim; nacubactam+cefepim; taniborbac-tam+cefepim, zidebactam+cefepim; relebactam+imipenem; vaborbactam+meropenem; xeruborbactam+avibactam; xeruborbactam+vaborbactam.

Introduction. Increasing resistance of microbes to antibiotics constitutes a public health issue. One of the major causes of resistance to beta-lactams has been reported to be the production of beta-lactamases. To counteract the inactivation of beta-lactams by beta-lactamases, beta-lactamase inhibitors have been developed. Objective. The aim of the study was to analyze and systematize the properties and mechanisms of action of beta-lactamase inhibitors in order to argue the prospects of combating resistance. Material and methods. A selection of articles published between 2018 and 2025 was carried out from the PubMed databases, followed by the subsequent analysis and systematization of data regarding the structure, properties, and mechanisms of action, using the keywords: beta-lactam antibiotics, beta-lactamases, mechanism of action, resistance. Results. It has been reported that microorganisms produce four classes of beta-lactamases: A, B, C and D. Class B is metallo-be-ta-lactamase, while the rest are serine beta-lactamases. Based on the study of the structure of beta-lactamases, beta-lactam beta-lactam beta-lactamase inhibitors have been developed: clavulanic acid, sulbactam, tazobactam, avi-bactam, relebactam, vaborbactam, taniborbactam, vabor-bactam, xeruborbactam, zidebactam; b) beta-lactamase inhibitors of non-beta-lactam structure: durlobactam, en-metazobactam, relebactam, nacubactam. The clinical use of beta-lactamase inhibitors has helped to combat beta-lactam resistance. Conclusion. The development of beta-lactamase inhibitors allowed to obtain combined antibacterial drugs: tazobactam+piperacillin; avibactam+ceftazidim; nacubactam+cefepim; taniborbactam+cefepim, zidebact-am+cefepim; relebactam+imipenem; vaborbactam+mero-penem; xeruborbactam+avibactam; xeruborbactam+vabor-bactam.