Microbiology Nuts & Bolts
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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.
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Timing of Samples and Target Levels

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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
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
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
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)
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