Steady-state pharmacokinetics and pharmacodynamics of cefepime administered by prolonged infusion in hospitalised patients

Int J Antimicrob Agents. 2011 Jan;37(1):46-50. doi: 10.1016/j.ijantimicag.2010.08.016. Epub 2010 Nov 11.


The objective of this study was to evaluate the steady-state pharmacokinetics and pharmacodynamics of cefepime administered by prolonged infusion in hospitalised patients requiring antimicrobial therapy. Nine patients received 1g every 8h (q8h), infused over 4h, and steady-state pharmacokinetic parameters were determined by non-compartmental and compartmental methods. Using these pharmacokinetic parameters, 5000-patient Monte Carlo simulations were performed to estimate the pharmacokinetic profiles for six prolonged-infusion dosing regimens. The probability of target attainment (PTA) was calculated at minimum inhibitory concentrations (MICs) ranging from 0.06 μg/mL to 32 μg/mL, and the cumulative fraction of response (CFR) was calculated for six Gram-negative pathogens using MIC data from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) (2005-2007, USA). The pharmacodynamic target was free cefepime concentrations remaining above the MIC for 60% of the dosing interval (60% fT>MIC). Mean ± standard deviation maximum and minimum serum concentrations, terminal elimination half-life, elimination rate constant, volume of distribution and systemic clearance of cefepime were 32.5 ± 13.5 μg/mL, 9.5 ± 5.2 μg/mL, 2.4 ± 0.7h, 0.316 ± 0.116 h(-1), 21.3 ± 6.5L and 6.6 ± 3.6L/h, respectively. At the susceptibility breakpoint of 8 μg/mL, the PTA was >90% for 1g and 2g q8h (4-h infusion) and 1g and 2g every 6h (q6h) (3-h infusion). For Pseudomonas aeruginosa, the CFR was 88.6% for 1g q8h (4-h infusion) and ≥ 92.7% for 2g q8h (4-h infusion) and 1g and 2g q6h (3-h infusion). Cefepime 1g q8h infused over 4h provides excellent target attainment for susceptible bacterial pathogens with MICs ≤8 μg/mL.

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics*
  • Cefepime
  • Cephalosporins / administration & dosage*
  • Cephalosporins / pharmacokinetics*
  • Female
  • Gram-Negative Bacterial Infections / drug therapy*
  • Hospitals
  • Humans
  • Infusions, Intravenous
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Models, Statistical
  • Monte Carlo Method
  • Plasma / chemistry
  • Time Factors


  • Anti-Bacterial Agents
  • Cephalosporins
  • Cefepime