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Neonatal infection can be acquired in utero transplacentally, through the birth canal during delivery (intrapartum), and from external sources after birth (postpartum).
In utero infection, which can occur any time before birth, results from overt or subclinical maternal infection. Consequences depend on the agent and timing of infection in gestation and include spontaneous abortion, intrauterine growth restriction, premature birth, stillbirth, congenital malformation (eg, rubella), and symptomatic neonatal infection (eg, cytomegalovirus [CMV], toxoplasmosis, syphilis).
Common viral agents include herpes simplex, HIV, CMV, and hepatitis B. Intrapartum infection with HIV or hepatitis B occurs from passage through an infected birth canal or by ascending infection if delivery is delayed after rupture of membranes; these viruses can less commonly be transmitted transplacentally. CMV is commonly transmitted transplacentally. Bacterial agents include group B streptococci, enteric gram-negative organisms (primarily Escherichia coli), gonococci, and chlamydiae.
Postpartum infections are acquired from contact with an infected mother either directly (eg, TB, which also is sometimes transmitted in utero) or through breastfeeding (eg, HIV, CMV) or from contact with health care practitioners and the hospital environment (numerous organisms—see Infections in Neonates: Neonatal Hospital-Acquired Infection).
Risk factors
Risk of contracting intrapartum and postpartum infection is inversely proportional to gestational age. Neonates are immunologically immature, with decreased polymorphonuclear leukocyte and monocyte function; premature infants are particularly so (see also Perinatal Physiology: Immunologic function). Maternal IgG antibodies are actively transported across the placenta, but effective levels for all organisms are not achieved until near term. IgM antibodies do not cross the placenta. Premature infants have decreased intrinsic antibody production and reduced complement activity. Premature infants are also more likely to require invasive procedures (eg, endotracheal intubation, prolonged IV access) that predispose to infection.
Symptoms and Signs
Symptoms and signs in neonates tend to be nonspecific (eg, vomiting, fever, petechiae, rashes, diarrhea, fever, hypothermia). Many congenital infections acquired before birth can cause or be accompanied by various symptoms or abnormalities (eg, growth restriction, deafness, microcephaly, anomalies, failure to thrive, hepatosplenomegaly, neurologic abnormalities).
Diagnosis
A wide variety of infections should be considered in neonates who are ill, febrile, or hypothermic. Infections such as congenital rubella, syphilis, toxoplasmosis, and CMV should be considered, particularly in neonates with abnormalities such as growth restriction, deafness, microcephaly, anomalies, failure to thrive, hepatosplenomegaly, or neurologic abnormalities.
Treatment
The primary treatment is usually antimicrobial therapy. Drug selection is similar to that in adults, because infecting organisms and their sensitivities are not specific to neonates. However, numerous factors, including age and weight, affect dose and frequency (see Table 1: Infections in Neonates: Recommended Dosages of Selected Parenteral Antibiotics for Neonates and Table 2: Infections in Neonates: Recommended Dosages of Selected Oral Antibiotics for Neonates*).
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Table 1
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| Recommended Dosages of Selected Parenteral Antibiotics for Neonates |
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Interval of Administration
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Antibiotic
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Route of Administration
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Individual Dose
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Body Weight < 1200 g
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Body Weight 1200 – 1999 g
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Body Weight ≥ 2000 g
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Age
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Age
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Age
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≤ 7 days
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8–28 days
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0–7 days
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≥ 8 days
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0–7 days
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≥ 8 days
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Comments
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Amikacin*
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IV, IM
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7.5–10 mg/kg
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q 18–24 h
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q 18–24 h
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q 12 h
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q 8 h
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q 12 h
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q 8 h
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Monitoring of serum drug levels required (peak = 20–30 μg/mL; trough =
< 10 μg/mL)
Dose reduction required for impaired renal function
For term neonates, may be given as a single dose of 15–20 mg/kg/day
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Amphotericin B
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IV
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0.25–1 mg/kg
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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 h to assess patient's febrile and hemodynamic response;† if no serious adverse effects are observed, infusion of a therapeutic dose (usually 0.25–1.25 mg/kg over 2–4 h), 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 K levels and hematologic and renal functions required
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Ampicillin
For meningitis
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IV
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50 mg/kg
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q 12 h
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q 12 h
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q 12 h
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q 8 h
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q 8 h
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q 6 h
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IV as 15– to 30-min infusion (≤ 10 mg/kg/min)
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For other diseases
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IV, IM
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25 mg/kg
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q 12 h
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q 12 h
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q 12 h
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q 8 h
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q 8 h
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q 6 h
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Aztreonam
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IV, IM
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30 mg/kg
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q 12 h
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q 12 h
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q 12 h
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q 8 h
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q 8 h
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q 6 h
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Limited data
For gram-negative bacilli only
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Cefazolin‡
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IV, IM
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20 mg/kg
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q 12 h
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q 12 h
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q 12 h
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q 12 h
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q 12 h
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q 8 h
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Limited data
No primary indication; not used as initial therapy for sepsis or meningitis
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Cefepime
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IV, IM
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30 mg/kg
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q 12 h
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q 12 h until age 14 days
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q 12 h
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q 12 h until age 14 days
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q 12 h
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q 12 h until age 14 days
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May be used for Pseudomonas aeruginosa infections
Sometimes used for meningitis, although usually as a 2nd-line drug and not always recommended
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50 mg/kg
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—
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q 8–12 h if age > 14 days
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—
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q 8–12 h if age > 14 days
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—
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q 8–12 h if age > 14 days
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Cefotaxime
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IV, IM
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50 mg/kg
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q 12 h
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q 8–12 h
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q 12 h
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q 8 h
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q 8–12 h
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q 6–8 h
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Often a first-line therapy for neonatal meningitis
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Ceftazidime
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IV, IM
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50 mg/kg
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q 12 h
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q 8 h
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q 12 h
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q 8 h
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q 8 h
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q 8 h
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Penetrates well into inflamed meninges
70–90% of drug excreted unchanged in urine
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Ceftriaxone
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IV, IM
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25–50 mg/kg
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q 24–36 h
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q 24–36 h
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q 24 h
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q 24 h
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q 24 h
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q 24 h
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Limited data
May cause biliary pseudolithiasis and, in jaundiced premature infants, may increase risk of bilirubin encephalopathy via displacement of bilirubin from albumin
Contraindicated for 48 h after the infusion of Ca-containing solutions in infants ≤ 28 days
For meningitis, 40–50 mg/kg q 12 h or 80–100 mg/kg q 24 h
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Chloramphenicol
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IV
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25 mg/kg
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q 24 h
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q 24 h
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q 24 h
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q 24 h
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q 24 h
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q 12 h
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Doses adjusted by monitoring serum drug levels and hematologic parameters
For meningitis, desired peak serum levels = 15–25 μg/mL and trough levels = 5–15 μg/mL
For other infections, dose adjusted to attain a peak level of 10–20 μg/mL and a trough level of 5–10 μg/mL
Large variability in serum levels and serum half life, especially in preterm neonates
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Clindamycin
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IV, IM
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5 mg/kg
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q 12 h
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q 12 h
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q 12 h
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q 8 h
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q 8 h
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q 6 h
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For anaerobes and gram-positive cocci (not enterococci)
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Gentamicin*
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IV, IM
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2.5 mg/kg
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q 18–24 h
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q 18–24 h
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q 12 h
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q 8–12 h
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q 12 h
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q 8 h
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Monitoring of serum drug levels required (peak = 4–12 μg/mL; trough = 0.5–2 μg/mL)
Dose reduction required for impaired renal function
Reduction in frequency (to q 18–24 h) for very small, premature infants
For term infants, possibly gentamicin 4 mg/kg q 24 h (peak serum levels are 2–3 times higher)
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Imipenem
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IV
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20–25 mg/kg
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q 18–24 h
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q 18–24 h
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q 12 h
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q 12 h
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q 12 h
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q 8 h
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Limited data
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Kanamycin*
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IV, IM
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7.5–10 mg/kg
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q 18–24 h
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q 18–24 h
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q 12–18 h
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q 8–12 h
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q 12 h
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q 8 h
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Monitoring of serum drug levels required (peak = 20–30 μg/mL; trough serum level should be < 10 μg/mL)
Dose reduction required for impaired renal function
Reduction in frequency (to q 18–24 h) required for very small, premature infants
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Metronidazole
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IV
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7.5 mg/kg
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q 24–48 h
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q 24–48 h
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q 24 h
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q 12 h
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q 12 h
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15 mg q 12 h
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Limited data
Loading dose of 15 mg/kg, then a subsequent dose 48 h later in preterm infants and 24 h later in term infants and then q 12 h
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Nafcillin
For meningitis or endocarditis
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IV
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50 mg/kg
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q 12 h
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q 12 h
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q 12 h
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q 8 h
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q 8 h
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q 6 h
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Monitoring of CBC and liver function required
Primarily excreted via the biliary tract
In jaundiced neonates, possible accumulation in serum, which may have adverse effects
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For other diseases
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IV, IM
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25 mg/kg
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q 12 h
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q 12 h
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q 12 h
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q 8 h
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q 8 h
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—
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37.5 mg/kg
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—
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—
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—
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—
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—
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q 6 h
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Oxacillin
For meningitis or endocarditis
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IV
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50 mg/kg
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q 12 h
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q 12 h
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q 12 h
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q 8 h
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q 8 h
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q 6 h
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For other diseases
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IV, IM
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25 mg/kg
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q 12 h
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q 12 h
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q 12 h
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q 8 h
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q 8 h
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—
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37.5 mg/kg
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—
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—
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—
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—
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—
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q 6 h
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Penicillin G, aqueous
For meningitis
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IV
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50,000–75,000 units/kg
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q 12 h
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q 12 h
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q 12 h
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q 8 h
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q 8 h
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q 6 h
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Maximum for group B streptococcal meningitis = 500,000 units/kg/day
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For most other diseases
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IV, IM
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25,000 units/kg
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q 12 h
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q 12 h
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q 12 h
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q 8 h
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q 8 h
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q 6 h
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Penicillin G, procaine
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IM
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50,000 units/kg
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Not recommended
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Not recommended
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q 24 h
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q 24 h
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q 24 h
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q 24 h
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Caution: Sterile abscess and procaine toxicity
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Piperacillin/Tazobactam
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IV (dose based on piperacillin component)
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50 mg/kg
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q 12 h
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—
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q 12 h
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—
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—
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—
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May be increased to 100 mg/kg q 6 h in infants > 28 days
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100 mg/kg
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—
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q 8 h
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—
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q 8 h
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q 12 h
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q 8 h
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Tobramycin*
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IV, IM
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2.5 mg/kg
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q 18–24 h
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q 18–24 h
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q 12 h
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q 8–12 h
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q 12 h
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q 8 h
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Monitoring of serum drug levels (peak = 4–12 μg/mL; trough serum level should be < 2 μg/mL)
Dose reduction required for impaired renal function
Reduction in frequency (to q 18–24 h) required for very small, premature infants
For term neonates, may be given as 4 mg/kg once/day (peak serum levels are 2–4 times higher with once/day dosing)
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Vancomycin
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IV
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10–15 mg/kg
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q 24 h
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q 24 h
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q 12–18 h
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q 8–12 h
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q 8–12 h
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q 6–8 h
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Loading dose of 15–20 mg/kg recommended by some clinicians
Given by slow IV infusion, over at least 60 min
Monitoring of serum trough level recommended (trough = 10–15 μg/mL)
Doses adjusted in patients with renal failure
For premature infants < 1000 g, 15 mg/kg q 24–36 h
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*Sample should be obtained 30 min after a 30-min IV infusion.
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†The need to administer a test dose of amphotericin B is controversial.
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‡
Cefazolin does not cross the blood-brain barrier.
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Table 2
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| Recommended Dosages of Selected Oral Antibiotics for Neonates* |
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Antibiotic
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Dosage
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Interval
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Comments
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Amoxicillin
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15 mg/kg
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q 8 h
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Limited data
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Azithromycin
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5–10 mg/kg
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q 24 h
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Preferred drug for treatment or prevention of pertussis in neonates < 1 mo
For treatment or prevention of pertussis, 10 mg/kg given once/day for 5 days
For most other infections, 10 mg/kg given on day 1 and then 5 mg/kg given on days 2–5
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Clindamycin†
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5 mg/kg
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q 6–8 h
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Limited data
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Erythromycin ethylsuccinate
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10 mg/kg
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q 6–12 h
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For chlamydial infections or pertussis in neonates > 1 mo
Associated with idiopathic hypertrophic pyloric stenosis
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Fluconazole
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3–6 mg/kg
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q 24–72 h
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For minor candidal infections, 6 mg/kg on day 1, then 3 mg/kg/dose q 24–72 h
For serious infections, 12 mg/kg once/day recommend for all gestational and postnatal ages
A first (loading) dose of 25 mg/kg also possibly considered
During the 1st 2 wk of life, adjustment of dosing interval possibly necessary if renal function is abnormal
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Flucytosine
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12.5–37.5 mg/kg
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q 6 h
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Limited data
Used only with amphotericin B to slow emergence of resistance
Monitoring of levels recommended
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Neomycin sulfate
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33 mg/kg
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q 8 h
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For gastroenteritis caused by enteropathogenic strains of Escherichia coli
May be systemically absorbed in neonates with severe diarrhea
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Rifampin
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10 mg/kg
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q 24 h
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For TB
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5 mg/kg
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q 12 h
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For meningococcus prophylaxis, given for 2 days
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10 mg/kg
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q 24 h
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For Haemophilus influenzae prophylaxis, given for 4 days
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*Unless otherwise stated, doses are for neonates who are > 7 days and > 2000 g.
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†The dose for neonates who are < 7 days old < 2000 g is 5 mg/kg q 12 h.
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In neonates, the 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 in premature infants may reduce antibiotic protein binding. Drugs that displace bilirubin from albumin (eg, sulfonamides, ceftriaxone) increase the risk of kernicterus.
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 GFR and renal tubular secretion during the first month of life necessitate dosing changes for other drugs (eg, penicillins, aminoglycosides, vancomycin).
Last full review/revision October 2009 by Mary T. Caserta, MD
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