Principles of monitoring antimicrobial blood concentrations

The aims of monitoring antimicrobial plasma concentrations are to maximise efficacy and minimise the risk of dose-related toxicity of drugs with a narrow therapeutic index (eg aminoglycosides, glycopeptides, antifungals). Monitoring may also be used to optimise dosage regimens in other circumstances (eg in patients with septic shock or who require intensive care support).

The clinical value of monitoring plasma concentrations is not well established for all antimicrobials. Monitoring recommendations and pharmacokinetic/pharmacodynamic clinical targets for commonly used antimicrobials contains a summary of whether therapeutic drug monitoring is required and pharmacokinetic/pharmacodynamic clinical targets for efficacy and toxicity for commonly used antimicrobials.

Monitoring antimicrobial concentrations in bodily fluids other than blood (eg cerebrospinal fluid) has been suggested to ensure target concentrations are achieved at the site of infection; however, the clinical value remains unproven.

In most cases, blood samples for antimicrobial concentration monitoring should be taken once steady state has been reached (usually after at least 5 half-lives of the drug if a loading dose was not given). Remeasure the concentration as required (eg once steady state has been reached after a dose was changed or an interacting drug was started or stopped).

Few laboratories perform assays of antimicrobials other than aminoglycosides and vancomycin; for a list of laboratories that perform other assays, see the Australian Society for Antimicrobials website.

Table 1. Monitoring recommendations and pharmacokinetic/pharmacodynamic clinical targets for commonly used antimicrobials
Abdul-Aziz 2020 Chau 2021
aminoglycosides: amikacin, gentamicin and tobramycin antifungals (systemic): fluconazole, flucytosine, isavuconazole, itraconazole, posaconazole, voriconazole antivirals: aciclovir and valaciclovir, ganciclovir and valganciclovir beta lactams quinolones linezolid teicoplanin vancomycin
aminoglycosides
amikacin, gentamicin and tobramycin
therapeutic drug monitoring recommendation	routine
target concentrations	see Monitoring aminoglycoside plasma concentrations
timing of sample in relation to starting drug or dose adjustment
timing of sample in relation to dose
antifungals (systemic)
fluconazole
therapeutic drug monitoring recommendation	not routinely recommended; consider in specific patient groups – see Monitoring fluconazole blood concentrations
target concentrations	seek expert advice
timing of sample in relation to starting drug or dose adjustment
timing of sample in relation to dose
flucytosine
therapeutic drug monitoring recommendation	routine – see Monitoring flucytosine blood concentrations
target concentrations	trough: 25 and 40 mg/L peak: less than 100 mg/L [NB1]
timing of sample in relation to starting drug or dose adjustment	after 3 to 5 days
timing of sample in relation to dose	trough concentration [NB3] peak concentration: 2 hours after an oral dose or 30 minutes after an intravenous dose
isavuconazole
therapeutic drug monitoring recommendation	not routinely recommended; consider in specific patient groups – see Monitoring isavuconazole blood concentrations
target concentrations	seek expert advice
timing of sample in relation to starting drug or dose adjustment
timing of sample in relation to dose
itraconazole
therapeutic drug monitoring recommendation	routine – see Monitoring itraconazole blood concentrations
target concentrations	prophylaxis: 0.5 to 4 mg/L [NB2] treatment: 1 to 4 mg/L [NB2]
timing of sample in relation to starting drug or dose adjustment	after 5 to 7 days
timing of sample in relation to dose	trough concentration [NB3]
posaconazole
therapeutic drug monitoring recommendation	routine – see Monitoring posaconazole blood concentrations
target concentrations	prophylaxis: more than 0.5 mg/L [NB4] treatment: more than 1 mg/L [NB4]
timing of sample in relation to starting drug or dose adjustment	after 5 to 7 days
timing of sample in relation to dose	trough concentration [NB3] [NB5]
voriconazole
therapeutic drug monitoring recommendation	routine – see Monitoring voriconazole blood concentrations
target concentrations	central nervous system infection, bulky disease, multifocal infection: 2 to 5 mg/L other infection: 1 to 4.5 mg/L
timing of sample in relation to starting drug or dose adjustment	after 2 to 5 days
timing of sample in relation to dose	trough concentration [NB3]
antivirals
aciclovir and valaciclovir
therapeutic drug monitoring recommendation	not routinely recommended; consider in specific patient groups – see Monitoring antiviral blood concentrations
target concentrations	seek expert advice
timing of sample in relation to starting drug or dose adjustment
timing of sample in relation to dose
ganciclovir and valganciclovir
therapeutic drug monitoring recommendation	not routinely recommended; consider in specific patient groups – see Monitoring antiviral blood concentrations
target concentrations	see Target ganciclovir plasma concentrations based on type of therapy
timing of sample in relation to starting drug or dose adjustment	seek expert advice
timing of sample in relation to dose	seek expert advice
beta lactams
therapeutic drug monitoring recommendation	not routinely recommended; consider in specific patient groups – see Monitoring beta-lactam blood concentrations
target concentrations	seek expert advice
timing of sample in relation to starting drug or dose adjustment
timing of sample in relation to dose
linezolid
therapeutic drug monitoring recommendation	not routinely recommended; consider in specific patient groups – see Monitoring linezolid blood concentrations
target concentrations	2 to 7 mg/L
timing of sample in relation to starting drug or dose adjustment	after 48 hours
timing of sample in relation to dose	trough concentration [NB3]
quinolones
therapeutic drug monitoring recommendation	not routinely recommended; consider in specific patient groups – see Monitoring quinolone blood concentrations
target concentrations	seek expert advice
timing of sample in relation to starting drug or dose adjustment
timing of sample in relation to dose
teicoplanin
therapeutic drug monitoring recommendation	routine – see Monitoring teicoplanin blood concentrations
target concentrations	severe, deep-seated methicillin-resistant Staphylococcus aureus (MRSA) infections: 20 to 50 mg/L MRSA bacteraemia: 20 to 40 mg/L other MRSA infection: 15 to 30 mg/L
timing of sample in relation to starting drug or dose adjustment	after 4 to 5 days
timing of sample in relation to dose	trough concentration [NB3]
vancomycin
therapeutic drug monitoring recommendation	routine
target concentrations	see Vancomycin monitoring and dosage adjustment in adults and Vancomycin monitoring and dosage adjustment in young infants and children
timing of sample in relation to starting drug or dose adjustment
timing of sample in relation to dose
Note: NB1: Higher flucytosine concentrations are associated with haematological toxicity and hepatotoxicity. NB2: Higher itraconazole concentrations are associated with gastrointestinal toxicity. NB3: A trough concentration is obtained by taking a sample directly before the subsequent dose is given. NB4: Some institutions recommend that the posaconazole plasma concentration should not exceed 4 mg/L because data show that posaconazole-induced pseudohyperaldosteronism can occur at concentrations of 4 mg/L or more. NB5: Random posaconazole plasma concentrations may also be used; consistent plasma concentrations occur over time.