Pharmacodynamic Targets

Literature-based PK/PD targets used to optimize antibiotic dosing. Antibiotics are classified into three pharmacodynamic patterns based on the relationship between drug exposure and bacterial killing.

Three PK/PD Killing Patterns
  • Time-dependent (%fT>MIC): Efficacy correlates with the percentage of the dosing interval that free drug concentrations remain above the MIC. Prolonged or continuous infusions maximize this parameter. Applies to beta-lactams.
  • AUC/MIC-dependent: Efficacy correlates with the ratio of the 24-hour area under the concentration–time curve to the MIC. Total daily exposure matters more than peak or duration. Applies to vancomycin, fluoroquinolones, daptomycin, linezolid.
  • Concentration-dependent (Cmax/MIC): Efficacy correlates with the ratio of peak concentration to MIC. Higher peaks drive faster bactericidal activity. Applies to aminoglycosides.

Table 1: Time-Dependent Killing (%fT>MIC)

Beta-lactam antibiotics — penicillins, cephalosporins, carbapenems

Drug Class Bacteriostatic Target Bactericidal Target Ref
Ampicillin Penicillin 30% 50% [1]
Penicillin G Penicillin 30% 50% [1]
Piperacillin/Tazobactam Penicillin + BLI 30% 50% [1]
Cefazolin Cephalosporin (1st gen) 35–40% 50–60% [1]
Ceftazidime Cephalosporin (3rd gen) 40% 60–70% [1]
Cefepime Cephalosporin (4th gen) 35–40% 60% [1], [6]
Ceftolozane/Tazobactam Cephalosporin + BLI 24–31% 32–42% [7]
Cefiderocol Siderophore cephalosporin 58–64% 73–75% [8]
Meropenem Carbapenem 20% 40% [1], [9]
Note: Targets expressed as %fT>MIC (percentage of dosing interval that free drug concentration exceeds the MIC). Carbapenems achieve bactericidal activity at lower %fT>MIC than penicillins or cephalosporins due to a more rapid rate of killing.

Table 2: AUC/MIC-Dependent Killing

Vancomycin, fluoroquinolones, daptomycin, linezolid

Drug PK/PD Target Clinical Goal Ref
Vancomycin AUC24/MIC 400–600 Serious MRSA infections; assumes MIC ≤1 mcg/mL [5]
Daptomycin AUC24/MIC ≥666 1-log bactericidal kill in murine thigh model [10]
Linezolid AUC24/MIC 80–120 Bacteriostatic; keep AUC24 <400 for safety (thrombocytopenia) [11]
Levofloxacin (Gram-negative) AUC24/MIC ≥125 Gram-negative infections [12]
Levofloxacin (Gram-positive) fAUC24/MIC ≥34 S. pneumoniae eradication [13]
Ciprofloxacin AUC24/MIC ≥125 Gram-negative infections [12]
Note: The 2020 ASHP/IDSA/SIDP vancomycin consensus guidelines recommend AUC-guided dosing (AUC24/MIC 400–600) over trough-based monitoring for serious MRSA infections.5 Fluoroquinolone AUC/MIC targets were derived from critically ill patient outcomes data.

Table 3: Concentration-Dependent Killing (Cmax/MIC)

Aminoglycosides

Drug PK/PD Target Typical Cmax Goal Ref
Gentamicin Cmax/MIC ≥8–10 8–10 mcg/mL [14], [15]
Tobramycin Cmax/MIC ≥8–10 8–10 mcg/mL [14], [15]
Amikacin Cmax/MIC ≥8–10 25–30 mcg/mL [14], [15]
Note: Aminoglycosides exhibit concentration-dependent killing with a significant post-antibiotic effect (PAE). Extended-interval (once-daily) dosing leverages both properties by maximizing Cmax/MIC while allowing drug-free intervals for reduced nephrotoxicity.

References

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