TABLE 1.
Demographic and Pharmacokinetic Data of Simulated Infant Populations
| Drug (Minimum GA Selected for Cohort) | Cefepimea (≥28 weeks GA) | Piperacillin/Tazobactama (≥23 weeks GA) | Tobramycina (≥30 weeks GA) |
|---|---|---|---|
| N | 988 | 999 | 951 |
| Gestational age at birth (weeks) | 32 (29, 36) | 29 (25, 33) | 33 (31, 36) |
| Birth weight (grams) | 1655 (1186, 2573) | 1068 (740, 1750) | 1781 (1417.5, 2500) |
| Postnatal age (days) | 19 (12, 31) | 17 (11, 30) | 16 (11, 25) |
| Postmenstrual age (weeks) | 35 (32, 38) | 31 (28, 35) | 35 (33, 38) |
| Weight (g) | 2060 (1449, 2890) | 1350 (910, 2021) | 2045 (1636.5, 2800) |
| Body surface area (m2) | 0.159 (0.127, 0.196) | 0.120 (0.093, 0.157) | 0.156 (0.136, 0.188) |
| Serum creatinine (mg/dL) | 0.40 (0.30, 0.60) | 0. 50 (0.37, 0.80) | 0.40 (0.30, 0.60) |
| Creatinine clearance (mL/min/1.75 m2)b | 35.5 (25.1, 52.8) | 25.1 (15.1, 41.3) | 35.1 (24.0, 52.8) |
| Volume (L/kg) | 0.65 (0.29, 0.67) | 0.62 (0.42, 0.91) | 1.1 (0.85, 1.55) |
| Clearance (L/hr/kg) | 0.18 (0.14, 0.24) | 0.11 (0.06, 0.21) | 0.09 (0.07, 0.13) |
| Neofax 2019 dosing used in simulation | Using piperacillin component | ||
| All PMA, ≤28 days PNA, 30 mg/kg/dose q12h | ≤29wk PMA, 8–28 days PNA, 100 mg/kg/dose q12h | 30–34wk PMA, 8–60 days PNA, 4 mg/kg/dose q24h | |
| All PMA, >28 days PNA, 50 mg/kg/dose q12h | ≤29wk PMA, 29–60 days PNA, 100 mg/kg/dose q8h | ≥35 wk PMA, 8–60 days old 4 mg/kg/dose q24 | |
| 30–36 wk PMA, 8–14 days PNA, 100 mg/kg/dose q12h | |||
| 30–36 wk PMA, 15–60 days PNA, 100 mg/kg q8h | |||
| 37–44 wk PMA, 8–60 days PNA, 100 mg/kg q8h | |||
| Pharmacokinetic model11,12,13 | Piperacillin component | ||
| Sample Size | 31 (Index group) 10 (Validation group) | 32 | 100 (Index group) 40 (Validation group) |
| Compartment | 1 | 1 | 1 |
| Variability | CL interindividual 36.87% Vd interindividual 40.8% Additive residual error 6.98 mg/L | CL interindividual 37% Proportional residual error 33% Additive residual error 6.90 mg/L Not determined for Vd | CL interindividual 25.8% Vd interindividual 21.9% Proportional residual error 19.2% |
| Vd | Vd = 4.12 * BSA | Vd = 0.42 * WTKG | Vd = 0.533 * WTKG |
| CL | CL = 0.457 * BSA + 0.243 * CLcr | CL = 0.08 * WTKG * (PMA/33)1.76 | CL = 0.0508 * WTKG (birthweight>2500g) CL = 0.0508 * WTKG * 0.843 (birthweight ≤2500g) |
a
Numbers, except for sample size and where indicated, represent median with interquartile range in parentheses.
b
Creatinine clearance was estimated using the Schwartz formula: CLcr = (k*height)/SCR where k=0.33 for preterm (<37wk) and low birth weight neonates (<2500g) until 1 year of age, k = 0.45 for full term neonates until 1 year old.19
BSA, body surface area my Mosteller formula; BW, birthweight; CL, clearance; CLcr, creatinine clearance GA, gestational age; N/A, not applicable or available; PMA, postmenstrual age; SCR, serum creatinine; Vd, volume of distribution; WTKG, weight in kg.