Pharmacokinetics of ticarcillin–clavulanate in premature infants

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.