Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants

作者：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 Jr; Laughon Matthew M^*

来源：Antimicrobial Agents and Chemotherapy, 2016, 60(5): 2888-2894.

DOI：10.1128/AAC.03086-15

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 mu g/ml in >90% of infants. There were no adverse events related to clindamycin use.

• 出版日期2016-5