Optimised dosing

During the last decade, considerable progress has been made in understanding pharmocokinetics (PK)
and pharmocodynamics (PD) relationships to identify an appropriate dosage regimen.

DosingU. Theuretzbacher, CID 2012

Because PK and PD are strongly connected, changes in either of these factors affect clinical outcome. In patients at risk for a high PK varaibility and reduced drug exposure or/and patients with a high likelihood of infection caused with pathogens with reduced susceptibility (higher MICs) optimising the dosing strategy improves reaching PK/PD targets that are predictive of clinical success.

Dosing optimisation strategies (U. Theuretzbacher, 2012):
Antibacterial Class PK/PD Index Predictive of Outcome Required Magnitude of PK/PD Index to Optimize Activity Dosing Strategy
β-Lactam antibiotics % ft>MIC % ft>MIC: 40%–70%, 80%–100% in immunocompromised patients Intravenous: prolonged infusion, continuous infusion; oral: more frequent dosing per day
Aminoglycosides AUC0–24/MIC and Cmax/MIC AUC0–24/MIC: >150 Once-daily administration, duration of therapy for ≤5–7 days, TDM
Glycopeptides: vancomycin fAUC0–24/MIC AUC0–24/MIC: >400 (total drug, protein binding 50 Dosing according to TDM
Lipopeptides: daptomycin fAUC0–24/MIC and fCmax/MIC AUC0–24/MIC: >800 (total drug, protein binding 90%) High once-daily dosing, TDM would be beneficial, not enough clinical data
Oxazolidinones: linezolid % ft>MIC and fAUC0–24/MIC AUC0–24/MIC: >100 and % t > MIC: > 85% (total drug, protein binding 30%) Dosing according to TDM to avoid treatment failure and dose-dependent toxicity
Quinolones fAUC0–24/MIC fAUC0-24/MIC: 70–90 and >250 for maximal effect High dosages, TDM may be beneficial

TDM: Therapeutic Drug Monitoring

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