Pharmacokinetics of ticarcillin-clavulanate in premature infants
02/2019
Journal Article
Authors:
Watt, K. M.;
Hornik, C. P.;
Balevic, S. J.;
Mundakel, G.;
Cotten, C. M.;
Harper, B.;
Benjamin, D. K., Jr.;
Anand, R.;
Laughon, M.;
Smith, P. B.;
Cohen-Wolkowiez, M.
Volume:
85
Pagination:
1021-1027
Issue:
5
Journal:
Br J Clin Pharmacol
PMID:
30710387
URL:
https://www.ncbi.nlm.nih.gov/pubmed/30710387
Keywords:
Clavulanic Acids/administration & dosage/pharmacokinetics
Computer Simulation
Dose-Response Relationship, Drug
Drug Dosage Calculations
Female
Humans
Infant, Extremely Premature
Infant, Newborn
Male
Microbial Sensitivity Tests
Models, Biological
Prospective Studies
Staphylococcal Infections/*drug therapy/microbiology
Staphylococcus/*drug effects/physiology
Ticarcillin/administration & dosage/pharmacokinetics
beta-Lactamase Inhibitors/administration & dosage/*pharmacokinetics
clavulanate
infants
pharmacokinetics
premature
ticarcillin
Abstract:
Ticarcillin-clavulanate covers a broad spectrum of pathogens that are common in premature infants. In infants <30 weeks gestational age, pharmacokinetic data to guide ticarcillin-clavulanate dosing are lacking. We enrolled 15 premature infants <30 weeks gestational age, determined pharmacokinetic parameters, and performed dosing simulations to determine optimal dosing for ticarcillin-clavulanate. The infants had a median (range) postnatal age (PNA) of 18 days (6-44 days) and gestational age of 25 weeks (23-28 weeks). Clearance was lower in infants with a PNA <14 days (0.050 L/kg/h [range 0.043-0.075]) compared with a PNA >/=14-45 days (0.078 L/kg/h [0.047-0.100]), consistent with maturation of renal function. Dosing simulations determined that ticarcillin 75 mg/kg q12h (PNA <14 days) or q8h (PNA >/= 14-45 days) achieved the target exposure for organisms with a minimum inhibitory concentration </=16 mu/mL in >90% of simulated infants. For highly resistant organisms (minimum inhibitory concentration 32 mug/mL), increased dosing frequency or extended infusion are necessary.
