Aminoglycoside Antibiotics

This test is used to monitor the level of the prescribed aminoglycoside antibiotic in the blood. The most common aminoglycoside antibiotics in the United States are amikacin, gentamicin or tobramycin. These drugs are used to treat serious bacterial infections. Testing is used to ensure that the level of the drug in the blood is sufficient to treat the infection but not so high as to increase the risk of side effects.

Measurements of blood levels are timed to reflect the highest concentration (peak) and the lowest concentration (trough) of the drug. These time points are used to evaluate the adequacy of dosing and monitor the clearance of the drug from the body.

In some cases, a dose of the drug is given only once every 24-48 hours (called extended-interval or pulse dosing). A test of the drug level on a sample taken 6-14 hours after the dose is used to ensure adequate dosing.

Blood drug levels are used by clinical pharmacists and healthcare providers to calculate the rate at which a person's body clears the drug from their blood. These results are then used to determine the appropriate amount of drug and the appropriate timing between doses to assure that the blood concentration is adequate for treating the infection but is not so high as to increase the risk of toxic side effects. For additional information on how the test is used, see Therapeutic Drug Monitoring.

Blood levels of gentamicin, tobramycin or amikacin may be monitored under a variety of conditions. For example, a person's age, kidney function, overall health, and presence of underlying conditions or symptoms of toxicity may be considered in the decision to perform the testing. The length of treatment and type of protocol used for dosing can also be factors.

Monitoring of aminiglycosides may be recommended when a person will be receiving the drug for more than 3 days. For interval dosing, testing is usually ordered after 2 to 4 doses of the aminoglycoside have been given and when the drug is expected to have reached a relatively stable level in the blood (steady state). Drug levels then may be measured again every few days or once a week and with any change in the amount or timing of the dose or with change in kidney function.

With individuals receiving extended interval dosing, no steady state of the drug will be achieved. Typically, a timed random sample is drawn 6 to 14 hours after the dose for testing.

Tests that evaluate kidney function, such as a creatinine test, are often performed at regular intervals during treatment with aminoglycosides. More frequent aminoglycoside monitoring may be performed for people with impaired kidney function (renal insufficiency) and for people who have an increased risk of toxic side effects, such as those taking other drugs known to adversely affect hearing and the kidneys (ototoxic or nephrotoxic).

When a dose of one of the aminoglycosides is given, the level typically rises in the blood to a peak concentration and then falls over time to a lower (trough) concentration. Sometimes these drugs are prescribed using interval dosing, in which the subsequent dose is timed to be given in anticipation of the falling level. The goal is to have a sufficient amount of drug in each dose to maintain a therapeutic level and kill the bacteria causing the infection. The dose and the dosing interval are optimized to give the body enough time to clear most of the drug from the previous dose before the next dose is given. This minimizes the risk of complications and helps ensure that an adequate drug level is always maintained in the blood.

For interval-dosing, a trough level of the aminoglycoside below the target level indicates that the person tested is clearing the drug at an adequate rate. A peak level within the therapeutic range means there should be sufficient drug in the blood to be effective. The target level typically depends on the type of infection and the organ infected. A peak concentration below the maximum level indicates that the treated person is at less risk of developing toxic side effects, though the person may still experience a complication.

If the trough and/or peak concentration is above the maximum level, then the person is at an increased risk of toxicity and the healthcare provider may either alter the dose or alter the dosing schedule.

For an extended-dose regimen, the results can help the healthcare provider decide when to give the next dose. In general, if the blood level is at the low end of the range, the health practitioner may decide to dose every 24 hours. If the level is at the higher end (indicating that the drug is being cleared more slowly), the health practitioner may wait 48 hours before giving the next dose.

If an individual's infection is not responding to the treatment, then the healthcare provider may either continue the drug for a longer period of time or consider other treatment options.

Intravenous doses of aminoglycosides are given slowly over about 30 minutes.

Other forms of aminoglycosides, such as eye drops, ear drops, and inhaled drugs, may be used to treat specific types of infections. Monitoring is not used in these cases.

The first aminoglycoside, streptomycin, was developed in the 1940s and used successfully to treat tuberculosis. Its use declined with the introduction of other aminoglycosides.

Aminoglycosides are cleared from the body by the kidneys, thus dosages are modified based upon kidney function. Tests that reflect the health of the kidneys, such as a creatinine or a creatinine clearance, are often ordered prior to the initiation of aminoglycoside therapy and then at intervals to monitor kidney function.

Risk of toxicity is increased in people who are taking other drugs that affect hearing and the kidneys such as certain diuretics, particularly furosemide, or NSAIDS (nonsteroidal anti-inflammatory drugs) such as ibuprofen or naproxen, or other antibiotics such as vancomycin.

Because of the potential for complications, extended-interval dosing is not recommended in people who:

• Are elderly (older than about 70 years of age)
• Are pregnant or have given birth recently
• Have renal insufficiency or pre-existing kidney disease
• Have serious liver disease
• Have extensive burns
• Have cystic fibrosis
• Have a history of impaired hearing and/or loss of balance

Although a person may receive intravenous aminoglycoside therapy at home, usually administered by a home health professional, blood levels cannot be monitored at home. The test requires specialized equipment and must be performed in a laboratory. The home health professional may draw a blood sample prior to administering the next dose of drug. This sample will be sent to a laboratory for analysis.