PMID- 28410277
OWN - NLM
STAT- MEDLINE
DCOM- 20170918
LR  - 20240407
IS  - 1532-0987 (Electronic)
IS  - 0891-3668 (Print)
IS  - 0891-3668 (Linking)
VI  - 36
IP  - 9
DP  - 2017 Sep
TI  - Use of Population Pharmacokinetics and Electronic Health Records to Assess 
      Piperacillin-Tazobactam Safety in Infants.
PG  - 855-859
LID - 10.1097/INF.0000000000001610 [doi]
AB  - BACKGROUND: Piperacillin, in combination with tazobactam, is frequently used in 
      infants for treating nosocomial infections, although safety data in this 
      population are limited. Electronic health record (EHR) data can be used to 
      evaluate drug safety in infants, but measures of drug exposure are lacking. 
      METHODS: To relate simulated piperacillin exposure with adverse events (AEs) in 
      infants using EHR data, we identified infants discharged from 333 neonatal 
      intensive care units managed by the Pediatrix Medical Group between 1997 and 
      2012. Using a previously published population pharmacokinetic model in the target 
      population, we simulated piperacillin steady state area under the concentration 
      versus time curve from zero to tau (AUCss,0-tau) and steady state maximal drug 
      concentration (Cmaxss). Next, we used multivariable logistic regression to 
      evaluate the association between simulated AUCss,0-tau and Cmaxss with clinical AEs 
      (seizure and rash) and laboratory AEs controlling for gestational age. The odds 
      ratios (95% confidence intervals) comparing the third versus the first tertiles 
      for AUCss,0-tau and Cmaxss were reported. RESULTS: We identified 746 infants with a 
      median (interquartile range) gestational age of 30 weeks (26-33) and postnatal 
      age of 11 days (6-25). The median (interquartile range) piperacillin dose was 
      225 mg/kg/d (176-300). No significant associations were found between simulated 
      piperacillin exposure (AUCss,0-tau and Cmaxss) and clinical and laboratory AEs. 
      CONCLUSIONS: We found no associations between predicted piperacillin exposures 
      and the occurrence of AEs. This study confirms the feasibility of using 
      population pharmacokinetics and EHR to relate drug exposure with safety.
FAU - Salerno, Sara
AU  - Salerno S
AD  - From the *Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman 
      School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, 
      North Carolina; daggerDepartment of Pediatrics, and double daggerDuke Clinical Research Institute, 
      Duke University Medical Center, Durham, North Carolina; and  section signPediatrix Medical 
      Group, Inc., Sunrise, Florida.
FAU - Hornik, Christoph P
AU  - Hornik CP
FAU - Cohen-Wolkowiez, Michael
AU  - Cohen-Wolkowiez M
FAU - Smith, P Brian
AU  - Smith PB
FAU - Ku, Lawrence C
AU  - Ku LC
FAU - Kelly, Matthew S
AU  - Kelly MS
FAU - Clark, Reese
AU  - Clark R
FAU - Gonzalez, Daniel
AU  - Gonzalez D
CN  - Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee
LA  - eng
GR  - UL1 TR001111/TR/NCATS NIH HHS/United States
GR  - K23 HD083465/HD/NICHD NIH HHS/United States
GR  - U01 FD004858/FD/FDA HHS/United States
GR  - UL1 TR002489/TR/NCATS NIH HHS/United States
GR  - L40 HD073040/HD/NICHD NIH HHS/United States
GR  - HHSN275201000003I/HD/NICHD NIH HHS/United States
GR  - T32 GM086330/GM/NIGMS NIH HHS/United States
GR  - UL1 TR001117/TR/NCATS NIH HHS/United States
GR  - HHSN275201000003C/AA/NIAAA NIH HHS/United States
GR  - HHSN272201500006C/AI/NIAID NIH HHS/United States
GR  - TL1 TR001110/TR/NCATS NIH HHS/United States
GR  - R01 HD076676/HD/NICHD NIH HHS/United States
GR  - T32 HD043029/HD/NICHD NIH HHS/United States
GR  - HHSN272201300017C/AI/NIAID NIH HHS/United States
GR  - HHSN272201300017I/AI/NIAID NIH HHS/United States
GR  - R18 FD005292/FD/FDA HHS/United States
GR  - K12 HD043494/HD/NICHD NIH HHS/United States
GR  - R21 HD080606/HD/NICHD NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Pediatr Infect Dis J
JT  - The Pediatric infectious disease journal
JID - 8701858
RN  - 0 (Anti-Bacterial Agents)
RN  - 157044-21-8 (Piperacillin, Tazobactam Drug Combination)
RN  - 87-53-6 (Penicillanic Acid)
RN  - X00B0D5O0E (Piperacillin)
SB  - IM
MH  - Anti-Bacterial Agents/*adverse effects/*therapeutic use
MH  - Area Under Curve
MH  - Cross Infection/*drug therapy/epidemiology
MH  - Electronic Health Records
MH  - Female
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Penicillanic Acid/adverse effects/*analogs & derivatives/therapeutic use
MH  - Piperacillin/adverse effects/therapeutic use
MH  - Piperacillin, Tazobactam Drug Combination
MH  - Retrospective Studies
PMC - PMC5555808
MID - NIHMS867793
EDAT- 2017/04/15 06:00
MHDA- 2017/09/19 06:00
PMCR- 2018/09/01
CRDT- 2017/04/15 06:00
PHST- 2017/04/15 06:00 [pubmed]
PHST- 2017/09/19 06:00 [medline]
PHST- 2017/04/15 06:00 [entrez]
PHST- 2018/09/01 00:00 [pmc-release]
AID - 10.1097/INF.0000000000001610 [doi]
PST - ppublish
SO  - Pediatr Infect Dis J. 2017 Sep;36(9):855-859. doi: 10.1097/INF.0000000000001610.