Aminoglycoside-modifying enzymes are grouped into three large families: nucleotidyl (adenyl)-transferases, phosphotransferases, and acetyltransferases (AACs), each with numerous variants. The two fundamental mechanisms of resistance to aminoglycosides in Enterobacterales are enzymatic modification or modification of their target. These promising results have led to approval by the European Medicines Agency and the Food and Drug Administration, but the drug has not yet been introduced to the market.Ĭlinicians must be aware of ESBL risk factors and coresistance to select appropriate antibiotics that may avoid the unnecessary use of aminoglycosides. These infections include bloodstream infections and hospital-acquired or ventilator-associated bacterial pneumonia. While the majority of data focus on complicated urinary tract infections, a multicenter, randomized, open-label trial has demonstrated that a definitive combination-therapy regimen with plazomicin, as compared to colistin, is effective in treating serious infections caused by carbapenem-resistant Enterobacterales. Plazomicin has the potential to fill a unique role in antimicrobial therapy due to the limited therapeutic options available for treating multidrug-resistant (MDR) pathogens. It is important to note that AGs are inherently inactive against Stenotrophomonas maltophilia and anaerobes. baumannii, both amikacin and tobramycin are the most frequently effective molecules. aeruginosa, tobramycin exhibits the most potent bactericidal activity among AGs and the lowest resistance rates. Consequently, amikacin is the optimal candidate for the empirical treatment of nosocomial infections or in situations where the prevalence of ESBL-producing strains is high. ESBL-producing strains remain susceptible to gentamicin and amikacin in approximately 50% and 70% of cases, respectively. For Enterobacterales, the three agents display comparable efficacy, with the exception of amikacin, the only AG active on Providencia spp., and gentamicin, to be preferred on Serratia marcescens. In contrast, amikacin displays higher MIC, which is offset by a reduced level of nephrotoxicity, thus allowing for higher serum concentrations.Īlthough gentamicin, tobramycin, and amikacin present a mostly similar microbiological spectrum of activity, some distinctions can be observed. Gentamicin and tobramycin exhibit comparable antimicrobial properties. The potent bactericidal activity exhibited by AGs can be attributed to their specific binding to the 30S ribosomal subunit, which effectively disrupts bacterial intracellular protein synthesis. Mechanism of Action and Spectrum of Activity In this review, we will discuss the advantages and pitfalls of the most commonly used AGs in the treatment of severely resistant Gram-negative organisms, namely amikacin, gentamicin, and tobramycin, as well as plazomicin, a promising next-generation aminoglycoside.Ģ. Due to their narrow therapeutic index, which entails risks of nephrotoxicity and ototoxicity, it is essential that AGs be prescribed within a strict framework of indications and administration schemes accompanied by careful monitoring. Indeed, a recent international survey indicated that short courses of AGs continue to be widely administered to critically ill patients with septic shock, despite wide variability in AG use. Furthermore, they demonstrate preserved minimum inhibitory concentrations (MICs) in difficult-to-treat (DTR) Gram-negative bacteria (GNB) such as Pseudomonas aeruginosa and Acinetobacter baumannii, as well as in pathogens with acquired resistance, including ESBL Enterobacterales. In the current medical landscape, AGs retain their status as an important component in the management of sepsis, owing to their rapid and potent bactericidal activity. Plazomicin, a next-generation aminoglycoside (2010), has an interesting bactericidal activity against most aminoglycoside-resistant strains such as extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Enterobacterales. Over time, several other AGs were identified, encompassing three molecules that remain commonly employed in contemporary medicine: gentamicin (1963), tobramycin (1967), and amikacin (1972). Streptomycin, the inaugural AG, was initially developed as an anti-tuberculosis agent. Aminoglycosides (AGs) represent a class of antibiotics that were first discovered in the mid-1940s and continue to be used extensively for the treatment of severe infections.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |