Therapeutic Drug Monitoring (TDM)
The majority of systemic antibiotics do not need to have their levels monitored however for others it is essential:
• Aminoglycosides - Gentamicin, Tobramycin, Amikacin
• Glycopeptides – Vancomycin, Teicoplanin (doses in excess of 400mg)
• Chloramphenicol (children under 4 years old, the elderly and those with hepatic impairment)
Antibiotic assays should be taken at the correct times, usually:
• Peak - 1 hour after administration
• Trough - immediately before administration of the next dose
Serum samples should be sent at the time of the 3rd or 4th dose, approximately 2-4 mls of blood = 1-2mls of serum, in red or yellow topped vacutainers. Subsequent levels should be checked twice weekly if renal function is stable or more frequently if renal function changes.
• Aminoglycosides - Gentamicin, Tobramycin, Amikacin
• Glycopeptides – Vancomycin, Teicoplanin (doses in excess of 400mg)
• Chloramphenicol (children under 4 years old, the elderly and those with hepatic impairment)
Antibiotic assays should be taken at the correct times, usually:
• Peak - 1 hour after administration
• Trough - immediately before administration of the next dose
Serum samples should be sent at the time of the 3rd or 4th dose, approximately 2-4 mls of blood = 1-2mls of serum, in red or yellow topped vacutainers. Subsequent levels should be checked twice weekly if renal function is stable or more frequently if renal function changes.
Timing of Samples and Target Levels
Gentamicin, Tobramycin and Amikacin
• Peak level (post-dose) in general assesses whether a therapeutic level has been achieved, therefore levels not required for once daily dosing
- If peak too low = dose inadequate therefore increase dose by approximately 10% (Graph
A, Diagrammatic Interpretation of TDM)
- If peak too high = dose too high therefore reduce dose by approximately 10% (Graph B, Diagrammatic Interpretation of TDM)
• Trough level (pre-dose) in general assesses whether toxic levels are accumulating
- If trough too high = patient is unable to eliminate the antibiotic quickly enough therefore
increase the time between doses, usually in 12 or 24 hour blocks of time (Graph C,
Diagrammatic Interpretation of TDM)
- In severe renal failure check levels daily and redose when target level achieved
• Peak level (post-dose) in general assesses whether a therapeutic level has been achieved, therefore levels not required for once daily dosing
- If peak too low = dose inadequate therefore increase dose by approximately 10% (Graph
A, Diagrammatic Interpretation of TDM)
- If peak too high = dose too high therefore reduce dose by approximately 10% (Graph B, Diagrammatic Interpretation of TDM)
• Trough level (pre-dose) in general assesses whether toxic levels are accumulating
- If trough too high = patient is unable to eliminate the antibiotic quickly enough therefore
increase the time between doses, usually in 12 or 24 hour blocks of time (Graph C,
Diagrammatic Interpretation of TDM)
- In severe renal failure check levels daily and redose when target level achieved
Vancomycin
• Peak level (post-dose) is not required, because the therapeutic effect is seen if antibiotic levels stay above 4xMIC for the microorganism, on trough measurement
• Trough level (pre-dose) target is 4xMIC for microorganism, which for most Gram-positive bacteria is 1-2mg/L i.e. target level needs to exceed 4-8mg/L (to allow for slight inaccuracies in
the timing of levels, laboratory reports state a target of 5-15mg/L). If antibiotic is being accumulated then trough levels rise in excess of 15mg/L with an associated risk of toxicity
- If trough too low = patient eliminating antibiotic too quickly therefore reduce time between
doses in 12 or 24 hour blocks of time (Graph D, Diagrammatic Interpretation of TDM)
- If trough too high = patient is unable to eliminate the antibiotic quickly enough therefore
increase the time between doses, usually in 12 or 24 hour blocks of time (Graph C,
Diagrammatic Interpretation of TDM)
- In severe renal failure check levels daily and redose when target level achieved
• Occasionally it is necessary to reduce the dose in order to avoid too frequent dosing but this should be discussed with a Microbiologist beforehand
• Peak level (post-dose) is not required, because the therapeutic effect is seen if antibiotic levels stay above 4xMIC for the microorganism, on trough measurement
• Trough level (pre-dose) target is 4xMIC for microorganism, which for most Gram-positive bacteria is 1-2mg/L i.e. target level needs to exceed 4-8mg/L (to allow for slight inaccuracies in
the timing of levels, laboratory reports state a target of 5-15mg/L). If antibiotic is being accumulated then trough levels rise in excess of 15mg/L with an associated risk of toxicity
- If trough too low = patient eliminating antibiotic too quickly therefore reduce time between
doses in 12 or 24 hour blocks of time (Graph D, Diagrammatic Interpretation of TDM)
- If trough too high = patient is unable to eliminate the antibiotic quickly enough therefore
increase the time between doses, usually in 12 or 24 hour blocks of time (Graph C,
Diagrammatic Interpretation of TDM)
- In severe renal failure check levels daily and redose when target level achieved
• Occasionally it is necessary to reduce the dose in order to avoid too frequent dosing but this should be discussed with a Microbiologist beforehand
Teicoplanin
• Levels are not normally required unless patient is on high doses (>400mg)
- If trough too low = patient is eliminating antibiotic too quickly therefore reduce time between
doses in 12 or 24 hour blocks of time (Graph D, Diagrammatic Interpretation of TDM)
- If trough too high = patient is unable to eliminate antibiotic quickly enough therefore increase
the time between doses usually in 12 or 24 hour blocks of time (Graph C, Diagrammatic
Interpretation of TDM)
- In severe renal failure check levels daily and redose when target level achieved
• Occasionally it is necessary to reduce the dose in order to avoid too frequent dosing but this
should be discussed with a Microbiologist beforehand
• Levels are not normally required unless patient is on high doses (>400mg)
- If trough too low = patient is eliminating antibiotic too quickly therefore reduce time between
doses in 12 or 24 hour blocks of time (Graph D, Diagrammatic Interpretation of TDM)
- If trough too high = patient is unable to eliminate antibiotic quickly enough therefore increase
the time between doses usually in 12 or 24 hour blocks of time (Graph C, Diagrammatic
Interpretation of TDM)
- In severe renal failure check levels daily and redose when target level achieved
• Occasionally it is necessary to reduce the dose in order to avoid too frequent dosing but this
should be discussed with a Microbiologist beforehand
Chloramphenicol
• Peak level (post-dose) in general assesses whether a therapeutic level has been achieved
- If peak too low = dose inadequate therefore increase dose by approximately 10% (Graph A,
Diagrammatic Interpretation of TDM)
- If peak too high = dose too high therefore reduce dose by approximately 10% (Graph B,
Diagrammatic Interpretation of TDM)
• Trough level (pre-dose) in general assesses whether toxic levels are accumulating
- If trough too high = patient is unable to eliminate antibiotic quickly enough therefore increase
the time between doses usually to TDS then BD (Graph C, Diagrammatic Interpretation of
TDM)
• Peak level (post-dose) in general assesses whether a therapeutic level has been achieved
- If peak too low = dose inadequate therefore increase dose by approximately 10% (Graph A,
Diagrammatic Interpretation of TDM)
- If peak too high = dose too high therefore reduce dose by approximately 10% (Graph B,
Diagrammatic Interpretation of TDM)
• Trough level (pre-dose) in general assesses whether toxic levels are accumulating
- If trough too high = patient is unable to eliminate antibiotic quickly enough therefore increase
the time between doses usually to TDS then BD (Graph C, Diagrammatic Interpretation of
TDM)
