Parenteral aminoglycoside therapy: Selection, administration and monitoring

Abstract

Aminoglycosides are potent water-soluble antibiotics, with peak concentration-dependent bactericidal activity against many pathogenic aerobic Gram-negative bacilli and Staphylococcus aureus. For systemic therapy, they must be given parenterally (intravenously or intramuscularly). In the body they remain largely extracellular, but penetration into cerebrospinal fluid and other secretions is meagre. They display trough concentration-dependent reversible nephrotoxicity and the commonly irreversible ototoxicity, which may present after treatment ceases. Gentamicin is the usual all-purpose agent of choice, tobramycin is slightly more effective against Pseudomonas aeruginosa infections, amikacin is the least susceptible to degradation by bacterial enzymes and netilmicin is probably the least toxic. Clinical and drug concentration monitoring have a role in therapy. Aminoglycosides exhibit enduring antibacterial activity (especially against Gram-negative bacilli) many hours after tissue concentrations become negligible. Appreciation of this postantibiotic effect is leading to replacement of conventional multiple daily doses by large single daily doses. The latter regimens confer at least equivalent efficacy and less risk of toxicity (particularly renal). However, single daily dosage may be unsuitable for immunocompromised patients and in those with infective-endocarditis, where-there is insufficient experience. Cotreatment with β-lactams is commonly used in order to exploit the synergism between these agents, particularly in enterococcal endocarditis and severe Gram-negative sepsis. Liposomal aminoglycosides are promising parenteral formulations. After being taken up by phagocytes they reach the liver, spleen and sites of inflammation; subsequently they are gradually released. To substantiate the applicability of these hitherto experimental formulations, findings from clinical studies are keenly awaited.