In neonates, the extracellular fluid (ECF) constitutes up to 45% of total body weight, requiring relatively larger doses of certain antibiotics (eg, aminoglycosides) compared with adults. Lower serum albumin concentrations inpremature infantsmay reduce antibiotic protein binding. Drugs that displace bilirubin from albumin (eg, sulfonamides, ceftriaxone) increase the risk ofkernicterus.
Absence or deficiency of certain enzymes in neonates may prolong the half-life of certain antibiotics (eg, chloramphenicol) and increase the risk of toxicity. Changes in glomerular filtration rate and renal tubular secretion during the first month of life necessitate dosing changes for renally excreted drugs (eg, penicillins, aminoglycosides, vancomycin).
(See also Overview of Neonatal Infections.)
Recommended Dosages of Selected Parenteral Antibiotics for Neonates
Intervals of Administration | |||||||
|---|---|---|---|---|---|---|---|
Antibiotic | Route of Administration | Individual Dose | Body Weight ≤ 2000 g | Body Weight > 2000 g | Comments | ||
Age | Age | ||||||
≤ 7 days | 8–28 days | ≤ 7 days | 8–28 days | ||||
Amikacin ( see Table: Recommended Dosages of Select Aminoglycosides for Neonates) | — | — | — | — | — | — | — |
Amphotericin B deoxycholate | IV | 1 mg/kg | Every 24 hours | Every 24 hours | Every 24 hours | Every 24 hours | After dilution in 5% or 10% D/W (saline solution should not be used), infusion of a test dose of 0.1 mg/kg (maximum 1 mg) over 1 hour to assess patient’s febrile and hemodynamic response;* if no serious adverse effects are observed, infusion of a therapeutic dose (usually 0.25–1.5 mg/kg over 2–6 hours), which may be given the same day as the test dose After the patient improves, may give the dose every other day until therapy is complete Monitoring of potassium levels and hematologic and renal functions required |
Amphotericin B lipid complex | IV | 5 mg/kg | Every 24 hours | Every 24 hours | Every 24 hours | Every 24 hours | — |
Amphotericin B liposomal | IV | 5 mg/kg | Every 24 hours | Every 24 hours | Every 24 hours | Every 24 hours | — |
Ampicillin | IV, IM | 50–75 mg/kg | 50 mg/kg every 12 hours | 75 mg/kg every 12 hours | 50 mg/kg every 8 hours | 50 mg/kg every 8 hours | IV as 15- to 30-minute infusion (≤ 10 mg/kg/minute) |
For GBS meningitis | IV | 75–100 mg/kg | 100 mg/kg every 8 hours | 75 mg/kg every 6 hours | 100 mg/kg every 8 hours | 75 mg/kg every 6 hours | |
Azithromycin | IV | 10 mg/kg | Every 24 hours | Every 24 hours | Every 24 hours | Every 24 hours | For chlamydial pneumonia, 20 mg/kg every 24 hours |
Cefazolin‡ | IV, IM | 25 mg/kg | Every 12 hours | Every 8 hours† | Every 12 hours | Every 8 hours | Limited data No primary indication; not used as initial therapy for sepsis or meningitis |
Cefepime | IV, IM | 30–50 mg/kg | 30 mg/kg every 12 hours | 30 mg/kg every 12 hours | 50 mg/kg every 12 hours | 50 mg/kg every 12 hours | May be used for Pseudomonas aeruginosa infections (consider using 50 mg/kg every 8 hours for P. aeruginosa and other serious gram-negative pathogens) Sometimes used for meningitis, although usually as a 2nd-line drug and not always recommended |
Cefotaxime | IV, IM | 50 mg/kg | Every 12 hours | Every 8 hours† | Every 12 hours | Every 8 hours | Often a first-line therapy for neonatal meningitis |
Cefoxitin | IV, IM | 33–35 mg/kg | 35 mg/kg every 12 hours | 33 mg/kg every 8 hours† | 33 mg/kg every 8 hours | 33 mg/kg every 8 hours | — |
Ceftazidime | IV, IM | 50 mg/kg | Every 12 hours | Every 8 hours† | Every 12 hours | Every 8 hours | Penetrates well into inflamed meninges 70–90% of drug excreted unchanged in urine |
Ceftriaxone | IV, IM | 50 mg/kg | — | — | Every 24 hours | Every 24 hours | Limited data May cause biliary pseudolithiasis and, in jaundiced premature infants, may increase risk of bilirubin encephalopathy via displacement of bilirubin from albumin Contraindicated in neonates receiving or expected to receive infusions of calcium-containing solutions 2nd-line drug for meningitis, after the first week of life (40–50 mg/kg every 12 hours or 80–100 mg/kg every 24 hours) |
Cefuroxime | IV, IM | 50 mg/kg | Every 12 hours | Every 8 hours† | Every 12 hours | Every 8 hours | — |
Fluconazole | — | ||||||
For treatment | IV | 12 mg/kg | Every 24 hours | Every 24 hours | Every 24 hours | Every 24 hours | Loading dose of 25 mg/kg followed 24 hours later by maintenance dose listed |
For prophylaxis | IV | 6 mg/kg | Twice weekly | Twice weekly | Twice weekly | Twice weekly | |
Gentamicin, tobramycin ( see Table: Recommended Dosages of Select Aminoglycosides for Neonates) | — | — | — | — | — | — | — |
Meropenem | — | ||||||
For meningitis | IV | 40 mg/kg | Every 12 hours | Every 8 hours§ | Every 8 hours | Every 8 hours | |
For sepsis, intra-abdominal infection§ | IV | 20–30 mg/kg | 20 mg/kg every 12 hours | 20 mg/kg every 8 hours§ | 20 mg/kg every 8 hours | 30 mg/kg every 8 hours | |
Nafcillin, oxacillin | — | ||||||
For meningitis | IV, IM | 50 mg/kg | Every 12 hours | Every 8 hours† | Every 8 hours | Every 6 hours | Monitoring of CBC and liver tests required Excretion may be decreased due to renal and hepatic immaturity, leading to possible accumulation in serum, which may have adverse effects |
For other diseases | IV, IM | 25 mg/kg | Every 12 hours | Every 8 hours† | Every 8 hours | Every 6 hours | |
Oxacillin (see Nafcillin, oxacillin) | — | — | — | — | — | — | — |
Penicillin G, benzathine | IM | 50,000 units/kg | Every 24 hours | Every 24 hours | Every 24 hours | Every 24 hours | — |
Penicillin G, crystalline (aqueous) | — | ||||||
For congenital syphilis, other indications | IV | 50,000 units/kg | Every 12 hours | Every 8 hours | Every 12 hours | Every 8 hours | |
For GBS meningitis | IV | 100,000 units/kg | Every 6 hours | Every 6 hours | Every 6 hours | Every 6 hours | |
Penicillin G, procaine | IM | 50,000 units/kg | Every 24 hours | Every 24 hours | Every 24 hours | Every 24 hours | CAUTION: Sterile abscess and procaine toxicity |
Piperacillin/tazobactam | IV (dose based on piperacillin component) | 80–100 mg/kg | 100 mg/kg every 8 hours | 80 mg/kg every 6 hours║ | 80 mg/kg every 6 hours | 80 mg/kg every 6 hours | — |
Rifampin | IV | 10 mg/kg | Every 24 hours | Every 24 hours | Every 24 hours | Every 24 hours | |
Tobramycin ( see Table: Recommended Dosages of Select Aminoglycosides for Neonates) | — | — | — | — | — | — | — |
— | — | — | — | — | — | ||
* The need to administer a test dose of amphotericin B is controversial. | |||||||
† Use the dose for age ≤ 7 days until 14 days of age if the birth weight is < 1000 g. | |||||||
‡ Cefazolin does not cross the blood-brain barrier. | |||||||
§ Adjust dosage after 14 days of age instead of after 7 days of age. | |||||||
║ When postmenstrual age reaches > 30 weeks. | |||||||
CBC = complete blood count; GBS = group B streptococcus. | |||||||
Adapted from Bradley JS, Nelson JD: Nelson's Pediatric Antimicrobial Therapy, ed. 24. Itasca, American Academy of Pediatrics, 2018. | |||||||
Recommended Dosages of Select Aminoglycosides for Neonates
Interval of Administration | |||||||||
|---|---|---|---|---|---|---|---|---|---|
Aminoglycoside | Route of Administration | Individual Dose | < 30 Week Gestation | 30–34 Week Gestation | ≥ 35 Week Gestation | Comments | |||
Postnatal Age | Postnatal Age | Postnatal Age | |||||||
0–14 days | > 14 days | 0–10 days | > 10 days | 0–7 days | > 7 days | ||||
Amikacin* | IV, IM | 15–17 mg/kg | 15 mg/kg every 48 hours | 15 mg/kg every 24 hours | 15 mg/kg every 24 hours | 15 mg/kg every 24 hours | 15 mg/kg every 24 hours | 17.5 mg/kg every 24 hours | Monitoring of serum drug levels required Peak level target 20–35 mg/L (34.2–59.8 micromol/L) or 10 × MIC; trough < 7 mg/L (12 micromol/L) Dose reduction required for impaired renal function |
Gentamicin*, tobramycin | IV, IM | 4–5 mg/kg | 5 mg/kg every 48 hours | 5 mg/kg every 36 hours | 5 mg/kg every 36 hours | 5 mg/kg every 36 hours | 4 mg/kg every 24 hours | 5 mg/kg every 24 hours | Monitoring of serum drug levels required Peak level target 6–12 mg/L (12.5–25.1 micromol/L) or 10 × MIC; trough < 2 mg/L (4.2 micromol/L) Dose reduction required for impaired renal function |
* Sample should be obtained 30 minutes after a 30-minute IV infusion. | |||||||||
MIC = minimum inhibitory concentration. | |||||||||
Adapted from Bradley JS, Nelson JD: Nelson's Pediatric Antimicrobial Therapy, ed. 24. Itasca, American Academy of Pediatrics, 2018. | |||||||||
Vancomycin Dosage for Neonates
Serum Creatinine (mg/dL) | Dose* (IV) | Interval of Administration | |
|---|---|---|---|
≤ 28 Week Gestation | > 28 Week Gestation | ||
< 0.5 | < 0.7 | 15 mg/kg | Every 12 hours |
0.5–0.7 | 0.7–0.9 | 20 mg/kg | Every 24 hours |
0.8–1 | 1–1.2 | 15 mg/kg | Every 24 hours |
1.1–1.4 | 1.3–1.6 | 10 mg/kg | Every 24 hours |
> 1.4 | > 1.6 | 15 mg/kg | Every 48 hours |
* Dose is given by slow IV infusion, over at least 60 minutes. Begin with a 20 mg/kg loading dose. Ideally, adjust dosage to achieve 24 hours AUC:MIC of 400 mg • hours/L. If this calculation cannot be done, monitor serum trough level (target typically = 10–12 mcg/mL [6.9–8.3 micromol/L]). | |||
AUC = area under the plasma concentration–time curve; MIC = minimum inhibitory concentration. | |||
Adapted from Bradley JS, Nelson JD: Nelson's Pediatric Antimicrobial Therapy, ed. 24. Itasca, American Academy of Pediatrics, 2018. | |||
Recommended Dosages of Selected Oral Antibiotics for Neonates*
Interval of Administration | |||||||
|---|---|---|---|---|---|---|---|
Antibiotic | Dose | Body Weight ≤ 2000 g† | Body Weight > 2000 g | Comments | |||
Postnatal Age | Postnatal Age | ||||||
≤ 7 days | 8–28 days | ≤ 7 days | 8–28 days | ||||
Amoxicillin (may be combined with clavulanate) | 15 mg/kg | — | — | Every 12 hours | Every 12 hours | Limited data for use in neonates < 2000 g Higher doses may be used for severe infections or anthrax Use only the 125 mg/5 mL suspension if combined with clavulanate | |
Azithromycin | 10 mg/kg | Every 24 hours | Every 24 hours | Every 24 hours | Every 24 hours | Preferred drug for treatment or prevention of pertussis in neonates < 1 month 10 mg/kg given once/day for 5 days May be used for treatment of chlamydial ophthalmia, most commonly 20 mg/kg every 24 hours for 3 days Associated with idiopathic hypertrophic pyloric stenosis, but less commonly than with erythromycin | |
Erythromycin | 10 mg/kg | Every 6 hours | Every 6 hours | Every 6 hours | Every 6 hours | For chlamydial infections or pertussis in neonates > 1 month Associated with idiopathic hypertrophic pyloric stenosis | |
Fluconazole | Loading dose of 25 mg/kg followed 24 hours later by maintenance dose listed During the 1st 2 weeks of life, adjustment of dosing interval to every 48 hours may be necessary | ||||||
For treatment | 12 mg/kg | Every 24 hours | Every 24 hours | Every 24 hours | Every 24 hours | For minor candidal infections (eg, thrush), 6 mg/kg on day 1, then 3 mg/kg/dose every 24–72 hours | |
For prophylaxis | 6 mg/kg | Twice/week | Twice/week | Twice/week | Twice/week | ||
Rifampin | 10 mg/kg | Every 24 hours | Every 24 hours | Every 24 hours | Every 24 hours | For treatment Additional dosing regimens may be used for Haemophilus influenzae type b and meningococcal disease prophylaxis | |
* Unless otherwise stated, doses are for neonates (≤ 28 days postnatal age). | |||||||
† Use ≤ 7 days dosing until 14 days old if the birth weight is < 1000 g. | |||||||
Adapted from Bradley JS, Nelson JD: Nelson's Pediatric Antimicrobial Therapy, ed. 24. Itasca, American Academy of Pediatrics, 2018. | |||||||
