Population pharmacokinetics of meropenem in plasma and cerebrospinal fluid of infants with suspected or complicated intra-abdominal infections

P. Brian Smith, Michael Cohen-Wolkowiez, Lisa M. Castro, Brenda Poindexter, Margarita Bidegain, Joern Hendrik Weitkamp, Robert L. Schelonka, Robert M. Ward, Kelly Wade, Gloria Valencia, David Burchfield, Antonio Arrieta, Varsha Bhatt-Mehta, Michele Walsh, Anand Kantak, Maynard Rasmussen, Janice E. Sullivan, Neil Finer, Beverly S. Brozanski, Pablo SanchezJohn Van Den Anker, Jeffrey Blumer, Gregory L. Kearns, Edmund V. Capparelli, Ravinder Anand, Daniel K. Benjamin

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Suspected or complicated intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial agent with excellent activity against pathogens associated with intra-abdominal infections in this population. The purpose of this study was to determine the pharmacokinetics (PK) of meropenem in young infants as a basis for optimizing dosing and minimizing adverse events. METHODS: Premature and term infants <91 days old hospitalized in 24 neonatal intensive care units were studied. Limited PK sampling was performed following single and multiple doses of meropenem 20 to 30 mg/kg of body weight every 8 to 12 hours based on postnatal and gestational age at birth. Population and individual patient (Bayesian) PK parameters were estimated using NONMEM. RESULTS: In this study, 200 infants were enrolled and received the study drug. Of them, 188 infants with 780 plasma meropenem concentrations were analyzed. Their median (range) gestational age at birth and postnatal age at PK evaluation were 28 (23-40) weeks and 21 (1-92) days, respectively. In the final PK model, meropenem clearance was strongly associated with serum creatinine and postmenstrual age (clearance [L/h/kg] = 0.12*[(0.5/serum creatinine)**0.27]*[(postmenstrual age/32.7)**1. 46]). Meropenem concentrations remained >4 μg/mL for 50% of the dose interval and >2 μg/mL for 75% of the dose interval in 96% and 92% of patients, respectively. The estimated penetration of meropenem into the cerebrospinal fluid was 70% (5-148). CONCLUSIONS: Meropenem dosing strategies based on postnatal and gestational age achieved therapeutic drug exposure in almost all infants.

Original languageEnglish
Pages (from-to)844-849
Number of pages6
JournalPediatric Infectious Disease Journal
Volume30
Issue number10
DOIs
StatePublished - Oct 2011

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meropenem
Intraabdominal Infections
Cerebrospinal Fluid
Pharmacokinetics
Population
Anti-Infective Agents
Premature Infants
Gestational Age
Morbidity
Mortality
Pharmaceutical Preparations

Keywords

  • cerebrospinal fluid
  • necrotizing enterocolitis
  • premature infant

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Infectious Diseases
  • Microbiology (medical)

Cite this

Population pharmacokinetics of meropenem in plasma and cerebrospinal fluid of infants with suspected or complicated intra-abdominal infections. / Smith, P. Brian; Cohen-Wolkowiez, Michael; Castro, Lisa M.; Poindexter, Brenda; Bidegain, Margarita; Weitkamp, Joern Hendrik; Schelonka, Robert L.; Ward, Robert M.; Wade, Kelly; Valencia, Gloria; Burchfield, David; Arrieta, Antonio; Bhatt-Mehta, Varsha; Walsh, Michele; Kantak, Anand; Rasmussen, Maynard; Sullivan, Janice E.; Finer, Neil; Brozanski, Beverly S.; Sanchez, Pablo; Van Den Anker, John; Blumer, Jeffrey; Kearns, Gregory L.; Capparelli, Edmund V.; Anand, Ravinder; Benjamin, Daniel K.

In: Pediatric Infectious Disease Journal, Vol. 30, No. 10, 10.2011, p. 844-849.

Research output: Contribution to journalArticle

Smith, PB, Cohen-Wolkowiez, M, Castro, LM, Poindexter, B, Bidegain, M, Weitkamp, JH, Schelonka, RL, Ward, RM, Wade, K, Valencia, G, Burchfield, D, Arrieta, A, Bhatt-Mehta, V, Walsh, M, Kantak, A, Rasmussen, M, Sullivan, JE, Finer, N, Brozanski, BS, Sanchez, P, Van Den Anker, J, Blumer, J, Kearns, GL, Capparelli, EV, Anand, R & Benjamin, DK 2011, 'Population pharmacokinetics of meropenem in plasma and cerebrospinal fluid of infants with suspected or complicated intra-abdominal infections', Pediatric Infectious Disease Journal, vol. 30, no. 10, pp. 844-849. https://doi.org/10.1097/INF.0b013e31822e8b0b
Smith, P. Brian ; Cohen-Wolkowiez, Michael ; Castro, Lisa M. ; Poindexter, Brenda ; Bidegain, Margarita ; Weitkamp, Joern Hendrik ; Schelonka, Robert L. ; Ward, Robert M. ; Wade, Kelly ; Valencia, Gloria ; Burchfield, David ; Arrieta, Antonio ; Bhatt-Mehta, Varsha ; Walsh, Michele ; Kantak, Anand ; Rasmussen, Maynard ; Sullivan, Janice E. ; Finer, Neil ; Brozanski, Beverly S. ; Sanchez, Pablo ; Van Den Anker, John ; Blumer, Jeffrey ; Kearns, Gregory L. ; Capparelli, Edmund V. ; Anand, Ravinder ; Benjamin, Daniel K. / Population pharmacokinetics of meropenem in plasma and cerebrospinal fluid of infants with suspected or complicated intra-abdominal infections. In: Pediatric Infectious Disease Journal. 2011 ; Vol. 30, No. 10. pp. 844-849.
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T1 - Population pharmacokinetics of meropenem in plasma and cerebrospinal fluid of infants with suspected or complicated intra-abdominal infections

AU - Smith, P. Brian

AU - Cohen-Wolkowiez, Michael

AU - Castro, Lisa M.

AU - Poindexter, Brenda

AU - Bidegain, Margarita

AU - Weitkamp, Joern Hendrik

AU - Schelonka, Robert L.

AU - Ward, Robert M.

AU - Wade, Kelly

AU - Valencia, Gloria

AU - Burchfield, David

AU - Arrieta, Antonio

AU - Bhatt-Mehta, Varsha

AU - Walsh, Michele

AU - Kantak, Anand

AU - Rasmussen, Maynard

AU - Sullivan, Janice E.

AU - Finer, Neil

AU - Brozanski, Beverly S.

AU - Sanchez, Pablo

AU - Van Den Anker, John

AU - Blumer, Jeffrey

AU - Kearns, Gregory L.

AU - Capparelli, Edmund V.

AU - Anand, Ravinder

AU - Benjamin, Daniel K.

PY - 2011/10

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N2 - BACKGROUND: Suspected or complicated intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial agent with excellent activity against pathogens associated with intra-abdominal infections in this population. The purpose of this study was to determine the pharmacokinetics (PK) of meropenem in young infants as a basis for optimizing dosing and minimizing adverse events. METHODS: Premature and term infants <91 days old hospitalized in 24 neonatal intensive care units were studied. Limited PK sampling was performed following single and multiple doses of meropenem 20 to 30 mg/kg of body weight every 8 to 12 hours based on postnatal and gestational age at birth. Population and individual patient (Bayesian) PK parameters were estimated using NONMEM. RESULTS: In this study, 200 infants were enrolled and received the study drug. Of them, 188 infants with 780 plasma meropenem concentrations were analyzed. Their median (range) gestational age at birth and postnatal age at PK evaluation were 28 (23-40) weeks and 21 (1-92) days, respectively. In the final PK model, meropenem clearance was strongly associated with serum creatinine and postmenstrual age (clearance [L/h/kg] = 0.12*[(0.5/serum creatinine)**0.27]*[(postmenstrual age/32.7)**1. 46]). Meropenem concentrations remained >4 μg/mL for 50% of the dose interval and >2 μg/mL for 75% of the dose interval in 96% and 92% of patients, respectively. The estimated penetration of meropenem into the cerebrospinal fluid was 70% (5-148). CONCLUSIONS: Meropenem dosing strategies based on postnatal and gestational age achieved therapeutic drug exposure in almost all infants.

AB - BACKGROUND: Suspected or complicated intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial agent with excellent activity against pathogens associated with intra-abdominal infections in this population. The purpose of this study was to determine the pharmacokinetics (PK) of meropenem in young infants as a basis for optimizing dosing and minimizing adverse events. METHODS: Premature and term infants <91 days old hospitalized in 24 neonatal intensive care units were studied. Limited PK sampling was performed following single and multiple doses of meropenem 20 to 30 mg/kg of body weight every 8 to 12 hours based on postnatal and gestational age at birth. Population and individual patient (Bayesian) PK parameters were estimated using NONMEM. RESULTS: In this study, 200 infants were enrolled and received the study drug. Of them, 188 infants with 780 plasma meropenem concentrations were analyzed. Their median (range) gestational age at birth and postnatal age at PK evaluation were 28 (23-40) weeks and 21 (1-92) days, respectively. In the final PK model, meropenem clearance was strongly associated with serum creatinine and postmenstrual age (clearance [L/h/kg] = 0.12*[(0.5/serum creatinine)**0.27]*[(postmenstrual age/32.7)**1. 46]). Meropenem concentrations remained >4 μg/mL for 50% of the dose interval and >2 μg/mL for 75% of the dose interval in 96% and 92% of patients, respectively. The estimated penetration of meropenem into the cerebrospinal fluid was 70% (5-148). CONCLUSIONS: Meropenem dosing strategies based on postnatal and gestational age achieved therapeutic drug exposure in almost all infants.

KW - cerebrospinal fluid

KW - necrotizing enterocolitis

KW - premature infant

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