Table 2.
Neonatal antibiotic PK, safety, and efficacy trials
| Drug | N (ref) | Study Design | GA (weeks) | PNA (days) | Notable Findings |
|---|---|---|---|---|---|
| Metronidazole | 33 (50) | population PK, scavenged sampling, sparse sampling | 22–32 | 0–97 | 2–3-fold lower CL compared with adults; CL increased linearly with weight and nonlinearly with PMA |
| 24 (53) | population PK, DBS | 23–31 | 1–82 | CL increases 100% during first 2 weeks of life; CL 30–50% of adult CL | |
| Daptomycin | 20 (56) | scavenged sampling | 23–40 | 1–85 | CL in neonates similar to CL in 2–6-year-old children and >CL seen in older children and adults; neonates may need higher doses to achieve comparable exposures |
| Clindamycin | 40 (57) | 28–40 | 2–357 | CL affected by PNA, GA, and weight; half-life prolonged in premature infants <4 weeks; half-life in term infants comparable to adults | |
| 12 (58) | 26–39 | 1–24 | CL lower in neonates than in older children and adults | ||
| Piperacillin-tazobactam | 56 (52) | population PK, sparse sampling, scavenged sampling | 22–32 | 1–77 | CL increases with allometrically scaled body weight and decreases proportionally with serum creatinine |
| 71 (59) | population PK, sparse sampling, | 26–41 | 1–56 | CL in infants <2 months is 66–75% of CL in infants 2–5 months of age; CL positively correlated with birth weight and PNA | |
| 32 (60) | population PK | 23–40 | 1–60 | CL increases 100% during first 2 weeks of life; CL in infants <2 months 60% lower than CL in older infants (term, 2–5 months), >75% lower than children | |
| Meropenem | 7 (61) | 27–32 | 5–44 | longer half-life in premature infants; adequate exposure with 15 mg/kg twice daily dosing | |
| 37 (62) | population PK, sparse sampling | 23–41 | 1–61 | CL positively correlated with PNA, birth GA, and PMA; CL negatively correlated with serum creatinine | |
| 38 (63) | population PK | 29–42 | 2–28 | CL depended most on serum creatinine and weight; CL substantially higher in term infants compared with premature infants | |
| 188 (64) | population PK | 23–40 | 1–92 | CL strongly associated with serum creatinine and PMA; infant CL about 30–40% lower than adult values; PK parameters similar to prior studies; 70% CSF penetration | |
| 19 (65) | population PK | ≤32 | ≤56 | similar PK parameters with both short infusion (30 minutes) and prolonged infusion (4 hours) | |
| 200 (66) | population PK, scavenged sampling, sparse sampling | 23–40 | 1–92 | well tolerated in infants; no adverse events probably or definitely related to meropenem; 84% overall therapeutic success rate |
CL, clearance; CSF, cerebrospinal fluid; DBS, dried blood spot sampling; GA, gestational age; PK, pharmacokinetic; PMA, postmenstrual age; PNA, postnatal age.