Article date: May 2019
By: Kevin M. Watt, Christoph P. Hornik, Stephen J. Balevic, Gratias Mundakel, C. Michael Cotten, Barrie Harper, Daniel K. Benjamin, Ravinder Anand, Matthew Laughon, P. Brian Smith, Michael Cohen‐Wolkowiez, on behalf of the Best Pharmaceuticals for Children Act — Pediatric Trials Network Steering Committee, on behalf of the Best Pharmaceuticals for Children Act — Pediatric Trials Network Steering Committee in Volume 85, Issue 5, pages 1021-1027
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 μ/mL in >90% of simulated infants. For highly resistant organisms (minimum inhibitory concentration 32 μg/mL), increased dosing frequency or extended infusion are necessary.
DOI: 10.1111/bcp.13882
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