PMID- 18645546
OWN - NLM
STAT- MEDLINE
DCOM- 20081002
LR  - 20220321
IS  - 0891-3668 (Print)
IS  - 0891-3668 (Linking)
VI  - 27
IP  - 9
DP  - 2008 Sep
TI  - Meropenem pharmacokinetics, pharmacodynamics, and Monte Carlo simulation in the 
      neonate.
PG  - 794-9
LID - 10.1097/INF.0b013e318170f8d2 [doi]
AB  - BACKGROUND: Hospitalized neonates are exposed to antibiotic-resistant bacterial 
      pathogens and develop nosocomial infections. Limited data are available regarding 
      the neonatal pharmacokinetics of meropenem, a broad spectrum carbapenem 
      antibiotic. METHODS: Neonates <2 months of age received a single dose of 
      meropenem at 10 or 20 mg/kg. Meropenem serum concentrations were measured at 
      specified times during the 24 hours postinfusion. Population pharmacokinetics 
      (PPK) were evaluated using NONMEM. Using Monte Carlo simulation (MCS), the 
      probability of pharmacokinetic-pharmacodynamic target attainment was evaluated by 
      computer modeling from predictions extrapolated from PPK data, using "virtual" 
      dosing regimens of 10, 20, and 40 mg/kg administered every 8 or 12 hours against 
      community- and hospital-acquired pathogens. RESULTS: Thirty-seven neonates were 
      enrolled, 22 were born at <36 weeks (range, 23-41 weeks) gestational age. 
      Meropenem clearance was greater in neonates with older chronologic ages and in 
      those born at later gestational ages. Serum creatinine and postconceptional age 
      (PCA) were the best overall predictors of meropenem elimination: CL (L/h/kg) = 
      0.041 + 0.040/SCr + 0.003 x (PCA-35). MCS demonstrated that in infants during the 
      first 2 weeks of life, a dosage of 20 mg/kg/dose every 8 hours achieved the 
      desired PD target in 95% of preterm neonates and 91% of term neonates against 
      Pseudomonas aeruginosa isolated from patients managed in adult and pediatric 
      intensive care units in the United States. CONCLUSIONS: MCS based on PPK 
      determinations demonstrated that a meropenem dose of 20 mg/kg every 8 hours 
      should provide adequate therapy for most nosocomial Gram-negative pathogens.
FAU - Bradley, John S
AU  - Bradley JS
AD  - Division of Infectious diseases, Children's Hospital and Health Center, San 
      Diego, CA 92123, USA. jbradley@chsd.org
FAU - Sauberan, Jason B
AU  - Sauberan JB
FAU - Ambrose, Paul G
AU  - Ambrose PG
FAU - Bhavnani, Sujata M
AU  - Bhavnani SM
FAU - Rasmussen, Maynard R
AU  - Rasmussen MR
FAU - Capparelli, Edmund V
AU  - Capparelli EV
LA  - eng
GR  - 5 U10 HD031318-14/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pediatr Infect Dis J
JT  - The Pediatric infectious disease journal
JID - 8701858
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Thienamycins)
RN  - AYI8EX34EU (Creatinine)
RN  - FV9J3JU8B1 (Meropenem)
SB  - IM
MH  - Age Factors
MH  - Anti-Bacterial Agents/administration & dosage/*pharmacokinetics
MH  - Computer Simulation
MH  - Creatinine/blood
MH  - Female
MH  - Gram-Negative Bacterial Infections/drug therapy
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Meropenem
MH  - Metabolic Clearance Rate
MH  - Monte Carlo Method
MH  - Serum/chemistry
MH  - Thienamycins/administration & dosage/*pharmacokinetics
MH  - United States
EDAT- 2008/07/23 09:00
MHDA- 2008/10/03 09:00
CRDT- 2008/07/23 09:00
PHST- 2008/07/23 09:00 [pubmed]
PHST- 2008/10/03 09:00 [medline]
PHST- 2008/07/23 09:00 [entrez]
AID - 10.1097/INF.0b013e318170f8d2 [doi]
PST - ppublish
SO  - Pediatr Infect Dis J. 2008 Sep;27(9):794-9. doi: 10.1097/INF.0b013e318170f8d2.