Once-daily dosing of aminoglycoside antibiotics

The aminoglycosides are a class of bactericidal antibiotics characterized by the presence of a six-carbon aminocyclitol ring covalently bonded to multiple amino sugar groups.(24) Aminoglycosides commonly used for the treatment of serious bacterial infections in the United States include gentamicin, tobramycin, amikacin, netilmicin, and streptomycin.(18) These drugs act in part by impairing bacterial protein synthesis through irreversible binding to the 30S subunit of the bacterial ribosome.(24) Since the introduction of streptomycin in the 1940s, aminoglycosides have proved extremely useful in the treatment of infections caused by gram-negative bacilli, including Pseudomonas aeruginosa, and infections caused by staphylococci, mycobacteria, and several other pathogens.(18) The Food and Drug Administration (FDA) approved dosing regimens for aminoglycoside antibiotics require multiple daily doses in individuals with normal renal function. Improvements in the understanding of the pharmacodynamics of aminoglycoside efficacy and mechanisms of toxicity, however, have prompted the evaluation of once-daily dosing regimens in clinical studies. In the pages that follow, we review the rationale behind once-daily dosing of aminoglycoside therapy as well as clinical data on the efficacy and toxicity of once-daily dosing of aminoglycosides. We also review practical aspects of dosing and monitoring once-daily aminoglycoside therapy and issues complicating the use of these regimens in special populations (including children, adults with an altered volume of distribution for aminoglycosides, and individuals with renal dysfunction) and in certain illnesses (including bacterial endocarditis, neutropenia and fever, and cystic fibrosis).