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To monitor the level of an aminoglycoside antibiotic such as gentamicin, tobramycin, or amikacin in the blood to ensure adequate dosing and help avoid toxic side effects
At regular intervals during treatment with an aminoglycoside
A blood sample drawn from a vein in your arm
None, but timing of the sample for testing is important; follow your healthcare provider's directions.
Gentamicin, tobramycin and amikacin are aminoglycosides, a group of antimicrobials (antibiotics) that are used to treat serious bacterial infections. The level of the prescribed aminoglycoside in the blood is measured in order to adjust doses as necessary and ensure effective treatment while avoiding toxic side effects. (For more information about this, see the article on Therapeutic Drug Monitoring.)
Gentamicin, tobramycin, and amikacin are the most commonly prescribed aminoglycosides, and they are used to treat infections caused by certain types of Gram-negative bacteria as well as a few Gram-positive bacteria. (For more on these, see the article on the Gram stain).
It is important to monitor the concentration of aminoglycosides because their effectiveness depends on having an adequate level in the blood. Aminoglycosides are associated with serious toxic side effects, including damage to hearing and/or balance (ototoxicity) and acute kidney damage (nephrotoxicity). Though kidney damage caused by aminoglycosides is usually reversible, hearing and/or balance loss is frequently permanent. These side effects can occur at any time, but the risk is greater with elevated blood levels and when the drugs are given for an extended period of time.
Aminoglycosides are not well absorbed by the digestive system so they are typically be administered either through a needle into a vein (intravenously, IV) or by injection into a muscle (intramuscularly, IM). Aminoglycosides can be given using dosing intervals (such as every 8-12 hours) or given as a large single dose once every 24 to 48 hours (also called extended-interval or pulse dosing). The amount of an aminoglycoside given per dose depends on a variety of factors, including kidney function, other drugs the person may be taking, age, and weight.
For interval dosing, drug monitoring typically involves assessing the maximum concentration soon after a dose is given (called a peak level) and the minimum concentration just before the next dose is given (called a trough level). Depending on the measured concentration, the next dose of drug may be adjusted up or down. For example, a person with decreased kidney function may not be able to clear the drug out of his system efficiently, resulting in an increased concentration in the blood, so the dose may be adjusted lower or the drug may be given less frequently. On the other hand, if a person is given too little drug and is unable to maintain a sufficient level in the blood, it is unlikely that treatment will be effective.
For extended-interval dosing, testing may be performed similarly to interval dosing, using a peak sample and a sample taken 6-12 hours later, or testing can be performed on a single sample taken 6-14 hours after the first dose of antibiotic.
Aminoglycosides are sometimes prescribed alone but are often combined with other antibiotics. Monitoring the antibiotic blood level is especially important in the presence of other medications, as they can affect the ability of the body to process (metabolize) and clear the drug.
A blood sample is obtained by inserting a needle into a vein in the arm.
No test preparation is needed, but the timing of the blood sample is important. For interval dosing, trough levels are collected just prior to a person's next aminoglycoside dose. Peak levels are collected 30-45 minutes after the completion of an intravenous dose or 60 minutes after an intramuscular dose. For extended-interval dosing, the recommended collection time may vary, but the time of the completion of the last dose and the time of the blood sample collection will be recorded and compared. Follow the healthcare provider's directions for collection. It may be helpful to tell the laboratorian when the administration of the last dose was completed.
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:
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.
There are risks and benefits associated with almost all drug therapies. Aminoglycosides continue to be very effective at killing Gram-negative bacteria and sometimes these drugs are the best alternative for successfully treating serious infections.
No, not all antibiotics require monitoring. Unlike aminoglycosides, most antibiotics are not associated with significant side effects that are predictable with drug levels. They have a larger therapeutic range in which they are effective. Because of this, they can be prescribed based upon pre-established dosing schedules.
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