- Richard H Drew, PharmD, MS, FCCP
Richard H Drew, PharmD, MS, FCCP
- Professor, Campbell University College of Pharmacy and Health Sciences
- Associate Professor and Clinical Pharmacist, Infectious Diseases
- Duke University Medical Center
The aminoglycoside class of antibiotics consists of many different agents. Gentamicin, tobramycin, amikacin, streptomycin, neomycin, and paromomycin are approved by the US Food and Drug Administration (FDA) and available for clinical use in the United States. Of these, gentamicin, tobramycin, and amikacin are the most frequently prescribed for systemic administration. Plazomicin is an aminoglycoside currently under development in the United States for the treatment of multidrug-resistant organisms.
The most common clinical application (either alone or as part of combination therapy) of the aminoglycosides is in the treatment of serious infections caused by aerobic gram-negative bacilli [1,2]. While less common, aminoglycosides (in combination with other agents) have also been used for the treatment of select gram-positive infections. In addition, certain aminoglycosides have demonstrated clinically relevant activity against protozoa (paromomycin), Neisseria gonorrhoeae (spectinomycin, not available in the United States), and mycobacterial infections (tobramycin, streptomycin, and [most commonly] amikacin).
This topic will review basic issues related to the clinical use of systemic aminoglycosides, including mechanism of action, spectrum of activity, and adverse effects. Dosing and monitoring of aminoglycosides and administration in certain patients populations are discussed elsewhere. (See "Dosing and administration of parenteral aminoglycosides" and "Cystic fibrosis: Antibiotic therapy for lung disease", section on 'Aminoglycosides'.)
The multiple clinical settings in which the aminoglycosides may be used are also discussed separately in the appropriate topic reviews. (See "Gram-negative bacillary bacteremia in adults", section on 'Indications and rationale for combination therapy' and "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections", section on 'Intravenous antibiotics' and "Antimicrobial therapy of native valve endocarditis", section on 'Viridans streptococci and Streptococcus bovis'.)
MECHANISM OF ACTION
The aminoglycosides primarily act by binding to the aminoacyl site of 16S ribosomal RNA within the 30S ribosomal subunit, leading to misreading of the genetic code and inhibition of translocation [3,4]. The initial steps required for peptide synthesis, such as binding of mRNA and the association of the 50S ribosomal subunit, are uninterrupted, but elongation fails to occur due to disruption of the mechanisms for ensuring translational accuracy . The ensuing antimicrobial activity is usually bactericidal against susceptible aerobic gram-negative bacilli.
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- MECHANISM OF ACTION
- SPECTRUM OF ACTIVITY
- Gram-negative organisms
- Gram-positive organisms
- Gram-negative organisms
- CLINICAL USE
- Combination antibacterial therapy
- Antimycobacterial therapy
- Other aminoglycoside formulations
- PHARMACODYNAMICS AND KINETICS
- Post antibiotic effect
- Concentration-dependent killing
- Synergistic effect
- Absorption and time to peak levels
- Neuromuscular blockade
- DRUG INTERACTIONS