Aminoglycosides clinical applications

Montie T and Patamasucon P. Aminoglycosides the complex problem of antibiotic mechanisms and clinical applications. Eur J Clin Microbiol Infect Dis 14 85-87,1995. 

The remarkably successful clinical application of aminoglycoside antibiotics attracted the attention of many organic chemists. With his continuous interest in this field for more than 20 years, Sumio Umezawa accomplished the first total synthesis of many aminoglycosides, including paromamine,- neamine," trehalosamine, kanamycins A, B, and C, 2 butirosin B, tobramycin, " streptomycin, dihydrostreptomycin, and neomycins B and C. ... 

The article by Miyake (Kawasaki), Maeda (Tokyo), and this writer details the long career of Sumio Umezawa devoted to the chemistry and medicinal applications of antibiotics, especially the aminocycUtols (aminoglycosides), afield dominated by Sumio and his microbiologist/biochemist brother Hamao from the earliest days of streptomycin through to practical semisynthetic analogues developed by Sumio that have enjoyed wide clinical application. The complementary articles by the two Umezawa brothers in Volume 30 of this series remain a definitive reference work on these antibiotics. 

List the major clinical applications of aminoglycosides and describe their main toxic effects. Describe the pharmacokinetics of this drug class, with special reference to the importance of renal clearance and its relationship to toxicity. 

Aminoglycosides remain clinically important antibiotics. NMR provided the initial breakthrough in structural understanding of aminoglycoside action on the ribosome, and it remains a powerful tool for the biophysical characterization of drug-RNA interaction. The combined use of NMR, X-ray crystallography, thermodynamic and functional assays, and computational methods is needed to drive forward the development of new aminoglycosides with improved clinical properties. The rich data described above, combined with the application of new synthetic methods, bode well for the future. 

Aminoglycoside-induced neuromuscular blockade can be clinically relevant in patients with respiratory acidosis, in myasthenia gravis, and in other neuromuscular diseases. Severe illness, the simultaneous use of anesthetics, for example in the immediate postoperative phase, and the application of the antibiotic to serosal surfaces are predisposing factors to be considered (15). Severe clinical manifestations are rare in patients treated with aminoglycosides that are administered in low doses, such as tobramycin. 

Further antibiotics, mainly derived from actinomycetes, are used for special applications in human and veterinary medicine [20]. These compounds have numerous chemical structures. The macrolides, tetracyclines, aminoglycosides, glycopeptides, and ansamycins for instance are used in antibacterial treatment whereas the anthracyclines reached the market to supplement anticancer chemotherapy. The fairly toxic polyether-type antibiotics are preferably used as anticoccidial agents. Due to the dramatically increasing resistance of clinical important bacterial strains new targets for the discovery of novel types of antibacterial agents are urgently needed. 

Since tobramycin is a broad-spectrum antibiotic its application may be followed by bacterial colonization of the patient with resistant organisms (27 ). So far, the clinical use of tobramycin has only occasionally been reported to be followed by the development of bacterial resistance. On theoretical grounds and on the basis of a comparison with gentamicin it can be presumed that widespread or indiscriminate use of tobramycin will be associated with the risk of the development of bacterial resistance due to resistance factor coding for a number of bacterial enzymes inactivating aminoglycosides and probably other antibiotics as well. 

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