Clindamycin pharmacokinetics and safety in preterm and term infants

Daniel Gonzalez, Paula Delmore, Barry T. Bloom, C. Michael Cotten, Brenda B. Poindexter, Elisabeth McGowan, Karen Shattuck, Kathleen K. Bradford, P. Brian Smith, Michael Cohen-Wolkowiez, Maurine Morris, Wanrong Yin, Daniel K. Benjamin, Matthew M. Laughon, Katherine Y. Berezny, Gregory L. Kearns, Ian M. Paul, Michael J. Smith, John Van Den Anker, Kelly Wade

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2888-2894
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume60
Issue number5
DOIs
StatePublished - May 1 2016

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Clindamycin
Premature Infants
Pharmacokinetics
Safety
Methicillin-Resistant Staphylococcus aureus
Population
Staphylococcus aureus
Sepsis
Pediatrics

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

Gonzalez, D., Delmore, P., Bloom, B. T., Cotten, C. M., Poindexter, B. B., McGowan, E., ... Wade, K. (2016). Clindamycin pharmacokinetics and safety in preterm and term infants. Antimicrobial Agents and Chemotherapy, 60(5), 2888-2894. https://doi.org/10.1128/AAC.03086-15

Clindamycin pharmacokinetics and safety in preterm and term infants. / Gonzalez, Daniel; Delmore, Paula; Bloom, Barry T.; Cotten, C. Michael; Poindexter, Brenda B.; McGowan, Elisabeth; Shattuck, Karen; Bradford, Kathleen K.; Smith, P. Brian; Cohen-Wolkowiez, Michael; Morris, Maurine; Yin, Wanrong; Benjamin, Daniel K.; Laughon, Matthew M.; Berezny, Katherine Y.; Kearns, Gregory L.; Paul, Ian M.; Smith, Michael J.; Van Den Anker, John; Wade, Kelly.

In: Antimicrobial Agents and Chemotherapy, Vol. 60, No. 5, 01.05.2016, p. 2888-2894.

Research output: Contribution to journalArticle

Gonzalez, D, Delmore, P, Bloom, BT, Cotten, CM, Poindexter, BB, McGowan, E, Shattuck, K, Bradford, KK, Smith, PB, Cohen-Wolkowiez, M, Morris, M, Yin, W, Benjamin, DK, Laughon, MM, Berezny, KY, Kearns, GL, Paul, IM, Smith, MJ, Van Den Anker, J & Wade, K 2016, 'Clindamycin pharmacokinetics and safety in preterm and term infants', Antimicrobial Agents and Chemotherapy, vol. 60, no. 5, pp. 2888-2894. https://doi.org/10.1128/AAC.03086-15
Gonzalez D, Delmore P, Bloom BT, Cotten CM, Poindexter BB, McGowan E et al. Clindamycin pharmacokinetics and safety in preterm and term infants. Antimicrobial Agents and Chemotherapy. 2016 May 1;60(5):2888-2894. https://doi.org/10.1128/AAC.03086-15
Gonzalez, Daniel ; Delmore, Paula ; Bloom, Barry T. ; Cotten, C. Michael ; Poindexter, Brenda B. ; McGowan, Elisabeth ; Shattuck, Karen ; Bradford, Kathleen K. ; Smith, P. Brian ; Cohen-Wolkowiez, Michael ; Morris, Maurine ; Yin, Wanrong ; Benjamin, Daniel K. ; Laughon, Matthew M. ; Berezny, Katherine Y. ; Kearns, Gregory L. ; Paul, Ian M. ; Smith, Michael J. ; Van Den Anker, John ; Wade, Kelly. / Clindamycin pharmacokinetics and safety in preterm and term infants. In: Antimicrobial Agents and Chemotherapy. 2016 ; Vol. 60, No. 5. pp. 2888-2894.
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