SYSTEMATIC STUDY OF AMINOGLYCOSIDE GROUP ANTIBIOTICS DRUG RESISTANCE

Zahraa A.H. AL-Tameemi*, Noor D. Almanaseer, Nesreen Ahmed Nasser

Aminoglycosides are powerful, broad-spectrum antibiotics that can cure infections that present a serious threat to life. Upon the seminal introduction of streptomycin in 1944, an array of pivotal medications such as kanamycin, gentamicin, and tobramycin subsequently emerged. This succession of compounds incontrovertibly affirmed the utility of this category of antibiotics in managing gram-negative bacterial infections. During the 1970s, the introduction of semi-synthetic aminoglycosides, including dibekacin, amikacin, and netilmicin, demonstrated the feasibility of developing therapeutics with diverse toxicological profiles and efficacy against strains displaying resistance mechanisms to earlier generation aminoglycosides. However, since that time, the rate of novel aminoglycoside development has significantly reduced. Contrarily, after a period of intensive scientific and clinical research, we now see these medications considerably differently from how people did when they were initially presented to the clinic. Antibiotic aminoglycoside resistance has significantly impacted clinical practice. The difficulty of resistance was one of the first faced by aminoglycosides, despite their potent bactericidal efficacy. The enzymatic alteration of the antibiotic is the most frequent form of clinically significant resistance against these treatments. Consequently, an enhanced comprehension of aminoglycoside-modifying enzymes and their interactions with antibiotics is essential to promote the development of superior inhibitors and innovative semi-synthetic aminoglycosides. These novel compounds should demonstrate increased potency and efficiency while remaining unaffected by modifying enzymes. In this review, we have aimed to cover the systematic study of aminoglycoside group antibiotics drug resistance with respect to different enzymes responsible for drug modification, and genetic traits involved in drug resistance. Our objective is to present and engage in discourse regarding these advancements, not with the intention to ascertain if new molecules or feasible methods for preventing bacterial resistance and drug-induced toxicity will ultimately be incorporated into clinical practice. Instead, we aim to inspire continuous research on aminoglycosides and to keep clinicians updated on the significant progress achieved in this field.