Short versus long infusion of meropenem in very-low-birth-weight neonates

Antimicrob Agents Chemother. 2012 Sep;56(9):4760-4. doi: 10.1128/AAC.00655-12. Epub 2012 Jun 25.


Prolonged infusion of meropenem has been suggested in studies with population pharmacokinetic modeling but has not been tested in neonates. We compared the steady-state pharmacokinetics (PK) of meropenem given as a short (30-min) or prolonged (4-h) infusion to very-low-birth-weight (gestational age, <32 weeks; birth weight, <1,200 g) neonates to define the appropriate dosing regimen for a phase 3 efficacy study. Short (n = 9) or prolonged (n = 10) infusions of meropenem were given at a dose of 20 mg/kg every 12 h. Immediately before and 0.5, 1.5, 4, 8, and 12 h after the 4th to 7th doses of meropenem, blood samples were collected. Meropenem concentrations were measured by ultrahigh-performance liquid chromatography. PK analysis was performed with WinNonlin software, and modeling was performed with NONMEM software. A short infusion resulted in a higher mean drug concentration in serum (C(max)) than a prolonged infusion (89 versus 54 mg/liter). In all but two patients in the prolonged-infusion group, the free serum drug concentration was above the MIC (2 mg/liter) 100% of the time. Meropenem clearance (CL) was not influenced by postnatal or postmenstrual age. In population PK analysis, a one-compartment model provided the best fit and the steady-state distribution volume (V(ss)) was scaled with body weight and CL with a published renal maturation function. The covariates serum creatinine and postnatal and gestational ages did not improve the model fit. The final parameter estimates were a V(ss) of 0.301 liter/kg and a CL of 0.061 liter/h/kg. Meropenem infusions of 30 min are acceptable as they balance a reasonably high C(max) with convenience of dosing. In very-low-birth-weight neonates, no dosing adjustment is needed over the first month of life.

Publication types

  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics
  • Chromatography, High Pressure Liquid
  • Creatinine / blood
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Dosage Calculations
  • Enterocolitis, Necrotizing / drug therapy
  • Enterocolitis, Necrotizing / microbiology
  • Female
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / growth & development
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / drug therapy*
  • Infant, Premature, Diseases / microbiology
  • Infant, Very Low Birth Weight
  • Infusions, Intravenous
  • Male
  • Meropenem
  • Models, Statistical*
  • Pneumonia / drug therapy
  • Pneumonia / microbiology
  • Sepsis / drug therapy
  • Sepsis / microbiology
  • Software*
  • Thienamycins / administration & dosage*
  • Thienamycins / blood
  • Thienamycins / pharmacokinetics


  • Anti-Bacterial Agents
  • Thienamycins
  • Creatinine
  • Meropenem