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Antibacterial resistance is increasing throughout the world, while the development of new agents is slowly progressing. In addition, the increasing prevalence of fluoroquinolone resistance may force many practitioners to choose an aminoglycoside agent in gram-negative regimens. Aminoglycosides are bactericidal agents with potent activity against gram-negative infections and activity against gram-positive infections when added to a cell wall active antimicrobial-based regimen. These agents may be dosed multiple times a day or consolidated as high-dose, extended-interval dosing to maximize pharmacokinetic and pharmacodynamic properties to achieve possible improved efficacy with reduced toxicity. Clinical application includes the treatment of bacteremia, endocarditis, health-care and nosocomial pneumonias, intra-abdominal infections, and others. Nephrotoxicity and ototoxicity are potential risks of aminoglycoside therapy that may be minimized with serum monitoring and short courses of therapy.