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The aminoglycoside antibiotics are widely used for the treatment of severe gram-negative infections such as pneumonia or bacteremia, often in combination with a β-lactam antibiotic. Aminoglycosides are also used for gram-positive infections such as infective endocarditis in combination with penicillins when antibiotic synergy is required for optimal killing. Aminoglycoside antibiotics available in the United States that are in common use include gentamicin, tobramycin, netilmicin, and amikacin.

Aminoglycoside antibiotics are bactericidal, and the drugs exhibit concentration-dependent bacterial killing.1 Antibiotics with concentration-dependent killing characteristically kill bacteria at a faster rate when drug concentrations are higher. Also, aminoglycosides have a concentration-dependent postantibiotic effect. The postantibiotic effect is the phenomenon of continued bacterial killing even though serum concentrations have fallen below the minimum inhibitory concentration (MIC). Because the postantibiotic effect is concentration-dependent for the aminoglycosides, higher drug concentrations lead to a longer postantibiotic effect. The mechanisms of action for aminoglycosides are binding to the 30S ribosomal subunit inhibiting protein synthesis and misreading of mRNA causing dysfunctional protein production.

The MIC for susceptible bacteria is higher for amikacin than it is for the other aminoglycosides. Because the pharmacokinetics is similar for all these drugs, higher doses of amikacin are needed to treat infections. The conventional method of dosing aminoglycoside antibiotics is to administer multiple daily doses (usually every 8 hours).2 In order to take advantage of concentration-dependent bacterial killing and the postantibiotic effect, extended-interval (usually the total daily dose given once per day) aminoglycoside administration is also a dosing option.3 Because of these two different methods of dosage administration, it is important to identify which is being used when discussing serum concentration monitoring.

Conventional Dosing

Aminoglycoside antibiotics are given as short-term (1/2–1 hour) infusions. If a 1-hour infusion is used, maximum end of infusion “peak” concentrations are measured when the infusion is completed (Figure 4-1). If a 1/2-hour infusion is used, serum concentrations exhibit a distribution phase so that drug in the blood and in the tissues are not yet in equilibrium. Because of this, a 1/2-hour waiting period is allowed for distribution to finish if a 1/2-hour infusion is used before peak concentrations are measured. Therapeutic steady-state peak concentrations for gentamicin, tobramycin, and netilmicin are generally 5–10 μg/mL for gram-negative infections. Infection sites with more susceptible bacteria, such as intra-abdominal infections usually can be treated with steady-state peak concentrations at the lower end of this range (typically 5–7 μg/mL). Infection sites that are difficult to penetrate and with bacteria that have higher MIC values, such as pseudomonal pneumonia usually require steady-state peak concentrations in the higher end of the range (typically 8–10 μg/mL). When gentamicin, tobramycin, or netilmicin are used synergistically with penicillins or other antibiotics for the treatment of gram-positive infections such as infective endocarditis steady-state peak concentrations of 3–5 μg/mL are often times adequate. Therapeutic peak concentrations ...

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