The present thesis work aims to examine from a clinical and epidemiological point of view the worrying problem of antibiotic-resistance and the emergence of multi-drug resistant bacterial strains, which have now become really common in hospitals. After a careful examination of these phenomena, especially in the Italian territory, and multiple mechanisms that make certain bacteria resistant to specific antibiotics, originally effective in the treatment of infections caused by the same pathogens, the possible strategies to stem antibiotic-resistance are here analyzed. This paper therefore focuses on the most promising new chemical compounds in the current pipeline, active against multi-resistant organisms, which are innovative compared to traditional antibiotics: firstly, the main antibacterial agents in clinical development (phase III), from 2017 to 2020, are listed (with special attention on the treatment of infections caused by pathogens Neisseria gonorrhoeae, including multi-drug-resistant isolates, and Clostridium difficile); and then it moves on to the newly agents of pharmacological interest that have been approved in the same period. They include tetracycline derivatives (Eravacycline), fourth generation fluoroquinolones (Delafloxacin), new beta-lactams (Meropenem and Vaborbactam; Cefiderocol), new aminoglycosides (Plazomicin), and agents in development for treating drug-resistant TB (Pretomanid). It concludes with the advantages than can result from the use of these compounds, also mentioning other approaches, still poorly developed, to combat antibiotic-resistance: nanoparticles as vehicle and release systems for antibiotics.
Il presente lavoro di tesi si propone di esaminare dal punto di vista clinico ed epidemiologico il preoccupante problema dell’antibiotico-resistenza e l’emergenza di ceppi batterici multi-drug resistant, divenuti ormai comuni in ambito ospedaliero. Dopo un’attenta disamina di tali fenomeni, in particolar modo nel territorio italiano e dei molteplici meccanismi che rendono certi batteri resistenti a specifici antibiotici, originariamente efficaci nel trattamento di infezioni causate dagli stessi patogeni, si analizzano le possibili strategie per arginare l’antibiotico-resistenza. L’elaborato si concentra dunque sui nuovi composti chimici più promettenti, attivi contro organismi multi-resistenti, che presentino innovatività rispetto agli antibiotici tradizionali: in primis, si elencano i principali farmaci in sviluppo clinico (fase III), dal 2017 al 2020 (con focus sul trattamento delle infezioni causate dai patogeni Neisseria gonorrhoeae multi-resistente e Clostridium difficile); per poi passare agli ultimi agenti di interesse farmacologico autorizzati al commercio nello stesso periodo. Si tratta di derivati delle tetracicline (Eravaciclina), fluorochinoloni di quarta generazione (Delafloxacina), nuovi antibiotici beta-lattamici (Meropenem e Vaborbactam; Cefiderocol), nuovi aminoglicosidici (Plazomicina), e farmaci utilizzati nel trattamento della tubercolosi multi-resistente (Pretomanid). Si conclude con i vantaggi che possono derivare dall’impiego di tali composti, accennando anche ad altri approcci per combattere l’antibiotico-resistenza, ancora poco sviluppati: le nanoparticelle come veicolo e sistemi di rilascio per principi attivi antibiotici.
Nuovi antibiotici contro ceppi batterici multi-drug resistant: ultimi sviluppi nella ricerca e prospettive future
TACCANI, MARINA
2020/2021
Abstract
The present thesis work aims to examine from a clinical and epidemiological point of view the worrying problem of antibiotic-resistance and the emergence of multi-drug resistant bacterial strains, which have now become really common in hospitals. After a careful examination of these phenomena, especially in the Italian territory, and multiple mechanisms that make certain bacteria resistant to specific antibiotics, originally effective in the treatment of infections caused by the same pathogens, the possible strategies to stem antibiotic-resistance are here analyzed. This paper therefore focuses on the most promising new chemical compounds in the current pipeline, active against multi-resistant organisms, which are innovative compared to traditional antibiotics: firstly, the main antibacterial agents in clinical development (phase III), from 2017 to 2020, are listed (with special attention on the treatment of infections caused by pathogens Neisseria gonorrhoeae, including multi-drug-resistant isolates, and Clostridium difficile); and then it moves on to the newly agents of pharmacological interest that have been approved in the same period. They include tetracycline derivatives (Eravacycline), fourth generation fluoroquinolones (Delafloxacin), new beta-lactams (Meropenem and Vaborbactam; Cefiderocol), new aminoglycosides (Plazomicin), and agents in development for treating drug-resistant TB (Pretomanid). It concludes with the advantages than can result from the use of these compounds, also mentioning other approaches, still poorly developed, to combat antibiotic-resistance: nanoparticles as vehicle and release systems for antibiotics.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/13102