Abstract

CLINICAL PHARMACOLOGY OF AMINOGLYCOSIDES IN INFANTS AND CHILDREN

Gian Maria Pacifici*

ABSTRACT

The aminoglycosides used in paediatric patients are gentamicin, tobramycin, amikacin, and streptomycin. Aminoglycosides are potent and useful antibiotics and their activity is mainly against aerobic gram-negative bacteria. Aminoglycosides are rapidly bactericidal being inhibitors of bacterial cell protein synthesis and the bacterial killing-rate is concentration dependent, the higher the concentration the greater bacterial killing-rate. The inhibitory activity of aminoglycosides persist after their serum concentrations fall below the MIC of bacteria a phenomenon known as the “post-antibiotic effect”. Aminoglycosides are used to treat urinary-tract infections, pneumonia, meningitis, peritonitis, bacterial endocarditis, tularaemia, plague,
mycobacterium infections, and infections caused by Pseudomonas aeruginosa in cystic fibrosis patients. Aminoglycosides are polar cations and are poorly absorbed by the gastrointestinal-tract whereas are rapidly absorbed following intramuscular injection. Aminoglycosides are rapidly cleared by glomerular filtration thus they accumulate in patients with impaired renal function and aminoglycosides may induce ototoxicity and nephrotoxicity. Aminoglycosides are eliminated mainly by renal route and the renal function increases with infant maturation and child development thus the clearance of aminoglycosides is age-dependent. Consequently, the dosing regimen of aminoglycosides must by adjusted in infants and children. Streptomycin and gentamicin are the recommended drugs to treat tularaemia and plague and streptomycin is employed to treat mycobacterium infections when Mycobacterium tuberculosis becomes resistant to other antibiotics. The aim of this study is to review the dosing, properties and therapeutic indications, variability of serum or plasma concentration, pharmacokinetics, interaction with drugs, ototoxicity, and nephrotoxicity in infants and children of gentamicin, tobramycin, amikacin, and streptomycin.

Keywords: Aminoglycosides, concentration, dosing, drug-interactions, nephrotoxicity, ototoxicity, pharmacokinetics, therapeutic-indications, and variability.