Chapter 16 : Aminocyclitol Aminoglycosides

Abstract:

This chapter gives an overview about aminocyclitol aminoglycosides. Aminoglycosides are rapidly bactericidal antibiotics, acting in particular on aerobic gram-negative bacilli, staphylococci, and gram-positive bacilli. The aminoglycosides are broad-spectrum antibiotics essentially active against gram-negative bacteria and staphylococci. A penicillin-aminoglycoside combination exerts synergistic and bactericidal activity on streptococci with low-level resistance to streptomycin. The antibiotics of the aminoglycoside family are bactericidal. Majority of studies relating to their mode of action have been undertaken with streptomycin. A number of studies have been conducted on the structure activity relationships of aminoglycosides. Certain bacteria may be naturally and consistently resistant to aminoglycosides. Resistance may be acquired by four different mechanisms: alteration of the target, interference with transport of the antibiotic, enzymatic inhibition of the antibiotic, and substitution of the target. The aminoglycosides can only be used parenterally, except for intestinal infections or indications for decontamination. Diffusion of the aminoglycosides is rapid. The apparent volume of distribution corresponds to 20 to 30% of body weight, a volume equivalent to that of the extracellular fluids. The pharmacokinetics of elimination of the aminoglycosides are dependent almost exclusively on renal function. The drug interactions observed with aminoglycosides are particularly detrimental when they are liable to exacerbate the specific toxic effects of aminoglycosides antibiotics: ototoxicity, nephrotoxicity, and curarizing effect. Aminoglycosides have both renal and cochleovestibular toxicity. Substantial progress has been made in terms of understanding the mechanisms of resistance and toxicity.