PARENTERAL AMINOGLYCOSIDE THERAPY - SELECTION, ADMINISTRATION AND MONITORING

Aminoglycosides are potent water-soluble antibiotics, with peak concen tration-dependent bactericidal activity against many pathogenic aerobi c Gram-negative bacilli and Staphylococcus aureus. For systemic therap y, they must be given parenterally (intravenously or intramuscularly). In the body they remain largely extracellular, but penetration into c erebrospinal fluid and other secretions is meagre. They display trough concentration-dependent reversible nephrotoxicity and The commonly ir reversible ototoxicity, which may present after treatment ceases. Gent amicin is the usual all-purpose agent of choice, tobramycin is slightl y more effective against Pseudomonas aeruginosa infections, amikacin i s the least susceptible to degradation by bacterial enzymes and netilm icin is probably the least toxic. Clinical and drug concentration moni toring have a role in therapy. Aminoglycosides exhibit enduring antiba cterial activity (especially against Gram-negative bacilli) many hours after tissue concentrations become negligible. Appreciation of this p ostantibiotic effect is leading to replacement of conventional multipl e daily doses by large single daily doses. The latter regimens confer at least equivalent efficacy and less risk of toxicity (partricularly renal). However, single daily dosage may be unsuitable for immunocompr omised patients and in those with infective endocarditis, where then i s insufficient experience. Cotreatment with beta-lactams is commonly u sed in order to exploit the synergism between these agents, particular ly in enterococcal endocarditis and severe Gram-negative sepsis. Lipos omal aminoglycosides are promising parenteral formulations. After bein g taken up by phagocytes they reach the liver, spleen and sites of inf lammation; subsequently they are gradually released. To substantiate t he applicability of these hitherto experimental formulations, findings from clinical studies are keenly awaited.