TY - JOUR
T1 - Clindamycin pharmacokinetics and safety in preterm and term infants
AU - Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee
AU - Gonzalez, Daniel
AU - Delmore, Paula
AU - Bloom, Barry T.
AU - Cotten, C. Michael
AU - Poindexter, Brenda B.
AU - McGowan, Elisabeth
AU - Shattuck, Karen
AU - Bradford, Kathleen K.
AU - Smith, P. Brian
AU - Cohen-Wolkowiez, Michael
AU - Morris, Maurine
AU - Yin, Wanrong
AU - Benjamin, Daniel K.
AU - Laughon, Matthew M.
AU - Berezny, Katherine Y.
AU - Kearns, Gregory L.
AU - Paul, Ian M.
AU - Smith, Michael J.
AU - Van Den Anker, John
AU - Wade, Kelly
N1 - Funding Information:
This study was funded under National Institute of Child Health and Human Development (NICHD) contracts HHSN275201000003I (principal investigator [PI] D. K. Benjamin) for the Pediatric Trials Network, HHSN27500013 (PI D. K. Benjamin) for the Pharmacokinetics of Antistaphylococcal Antibiotics in Infants study (Staph Trio; protocol NICHD-2012-STA01), HHSN27500006 (PIs C. Melloni and M. Cohen-Wolkowiez) for the Pharmacokinetics of Understudied Drugs Administered to Children per Standard of Care Study (PTN POPS; protocol NICHD-2011-POP01), and HHSN27500018 (PI K. Watt) for the Safety and Pharmacokinetics of Multiple-Dose Intravenous and Oral Clindamycin Pediatric Subjects with BMI ≥ 85th Percentile Study (CLIN01; protocol NICHD-2012-CLN01). Research reported in this publication was also supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) under award number UL1TR001117. D.G. received research support through 1K23HD083465-01 from the NICHD, and from the nonprofit organization Thrasher Research Fund (www.thrasherresearch.org). P.B.S. received salary support for research from the NIH and the National Center for Advancing Translational Sciences of the NIH (UL1TR001117), the NICHD (HHSN2752010000031 and 1R01-HD081044-01), and the Food and Drug Administration (1R18-FD005292-0I), as well as research support from Cempra Pharmaceuticals (subaward to HHSO100201300009C) and Industry for Neonatal and Pediatric Drug Development (www.dcri.duke.edu/research/coi.jsp). M.C.-W. received support for research from the NIH (1R01-HD076676-01A1), the National Center for Advancing Translational Sciences of the NIH (UL1TR001117), the National Institute of Allergy and Infectious Disease (NIAID; HHSN272201500006I and HHSN272201300017I), the NICHD (HHSN275201000003I), the Food and Drug Administration (1U01FD004858-01), the Biomedical Advanced Research and Development Authority (BARDA; HHSO100201300009C), and the nonprofit organization Thrasher Research Fund (www.thrasherresearch.org) and from industry (CardioDx and Durata Therapeutics) for drug development in adults and children (www.dcri.duke.edu/research/coi.jsp). D.K.B. received support from the United States government for his work in pediatric and neonatal clinical pharmacology (2K24HD058735-06, UL1TR001117, NICHD contract HHSN275201000003I, and NIAID contract HHSN272201500006I), as well as research support from Cempra Pharmaceuticals (subaward to HHSO100201300009C) for neonatal and pediatric drug development (www.dcri.duke.edu/research/coi.jsp). M.M.L. received support from the U.S. government for work in pediatric and neonatal clinical pharmacology (government contract HHSN267200700051C, PI D. K. Benjamin under the Best Pharmaceuticals for Children Act), from the NICHD (K23HD068497), and from Pfizer, Cempra, and Astellas for work on DSMBs. The remaining authors have no funding to disclose. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
PY - 2016/5
Y1 - 2016/5
N2 - Clindamycin may be active against methicillin-resistant Staphylococcus aureus, a common pathogen causing sepsis in infants, but optimal dosing in this population is unknown. We performed a multicenter, prospective pharmacokinetic (PK) and safety study of clindamycin in infants. We analyzed the data using a population PK analysis approach and included samples from two additional pediatric trials. Intravenous data were collected from 62 infants (135 plasma PK samples) with postnatal ages of < 121 days (median [range] gestational age of 28 weeks [23 to 42] and postnatal age of 17 days [1 to 115]). In addition to body weight, postmenstrual age (PMA) and plasma protein concentrations (albumin and alpha-1 acid glycoprotein) were found to be significantly associated with clearance and volume of distribution, respectively. Clearance reached 50% of the adult value at PMA of 39.5 weeks. Simulated PMA-based intravenous dosing regimens administered every 8 h (≤32 weeks PMA, 5 mg/kg; 32 to 40 weeks PMA, 7 mg/kg; > 40 to 60 weeks PMA, 9 mg/kg) resulted in an unbound, steady-state concentration at half the dosing interval greater than a MIC for S. aureus of 0.12 μg/ml in >90% of infants. There were no adverse events related to clindamycin use.
AB - Clindamycin may be active against methicillin-resistant Staphylococcus aureus, a common pathogen causing sepsis in infants, but optimal dosing in this population is unknown. We performed a multicenter, prospective pharmacokinetic (PK) and safety study of clindamycin in infants. We analyzed the data using a population PK analysis approach and included samples from two additional pediatric trials. Intravenous data were collected from 62 infants (135 plasma PK samples) with postnatal ages of < 121 days (median [range] gestational age of 28 weeks [23 to 42] and postnatal age of 17 days [1 to 115]). In addition to body weight, postmenstrual age (PMA) and plasma protein concentrations (albumin and alpha-1 acid glycoprotein) were found to be significantly associated with clearance and volume of distribution, respectively. Clearance reached 50% of the adult value at PMA of 39.5 weeks. Simulated PMA-based intravenous dosing regimens administered every 8 h (≤32 weeks PMA, 5 mg/kg; 32 to 40 weeks PMA, 7 mg/kg; > 40 to 60 weeks PMA, 9 mg/kg) resulted in an unbound, steady-state concentration at half the dosing interval greater than a MIC for S. aureus of 0.12 μg/ml in >90% of infants. There were no adverse events related to clindamycin use.
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U2 - 10.1128/AAC.03086-15
DO - 10.1128/AAC.03086-15
M3 - Article
C2 - 26926644
AN - SCOPUS:84964869727
SN - 0066-4804
VL - 60
SP - 2888
EP - 2894
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 5
ER -