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Overview of Neonatal Infections

by Mary T. Caserta, MD

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 (eg, cytomegalovirus [CMV], toxoplasmosis, syphilis) or asymptomatic (eg, CMV) neonatal infection.

Common viral agents include herpes simplex viruses, 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), Listeria monocytogenes, gonococci, and chlamydiae.

Postpartum infections are acquired from contact with an infected mother 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 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, monocyte, and cell-mediated immune function; premature infants are particularly so (see also 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 or poor feeding, increased sleepiness, fever or hypothermia, tachypnea, rashes, diarrhea). 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, including sepsis, should be considered in neonates who are ill at or shortly after birth, particularly those with risk factors. Infections such as congenital rubella, syphilis, toxoplasmosis, and CMV should be pursued in neonates with abnormalities such as growth restriction, deafness, microcephaly, anomalies, hepatosplenomegaly, or neurologic abnormalities.

Treatment

  • Antimicrobial therapy

The primary treatment for presumed bacterial infection in the neonate is 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 Recommended Dosages of Selected Parenteral Antibiotics for Neonates and see Table: Recommended Dosages of Selected Oral Antibiotics for Neonates*).

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).

Recommended Dosages of Selected Parenteral Antibiotics for Neonates

Interval of Administration

Antibiotic

Route of Administration

Individual Dose

Body Weight < 1200 g

Body Weight 1200 – 1999 g

Body Weight ≥ 2000 g

Comments

Age

Age

Age

≤ 7 days

8–28 days

≤ 7 days

8–28 days

≤ 7 days

8–28 days

Amikacin*

IV, IM

15 mg/kg

q 48 h

q 24–48 h

q 48 h

q 24–48 h

q 24 h

q 12–24 h

Monitoring of serum drug levels required (peak = 20–30 μg/mL; trough =< 10 μg/mL)

Dose reduction required for impaired renal function

For extended dosing intervals, may be given as a single dose of 15–20 mg/kg given once/day or once every 48 h

Amphotericin B deoxycholate

IV

0.25–1.5 mg/kg

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 0.25–1.5 mg/kg over 2–6 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

Ampicillin

For meningitis

IV

75 mg/kg

q 6 h

q 6 h

q 6 h

q 6 h

q 6 h

q 6 h

IV as 15- to 30-min infusion ( 10 mg/kg/min)

For other diseases

IV, IM

50 mg/kg

q 12 h

q 8 h

q 12 h

q 8 h

q 8 h

q 6 h

Aztreonam

IV, IM

30 mg/kg

q 12 h

q 12 h

q 12 h

q 8–12 h

q 8–12 h

q 6–8 h

Limited data

For gram-negative bacilli only

Cefazolin

IV, IM

20–25 mg/kg

q 12 h

q 12 h

q 12 h

q 12 h

q 12 h

q 8 h

Limited data

No primary indication; not used as initial therapy for sepsis or meningitis

Cefepime

IV, IM

30–50 mg/kg

q 12 h

q 8–12 h

q 12 h

q 8–12 h

q 8–12 h

q 8–12 h

May be used for Pseudomonas aeruginosa infections (consider using 50 mg/kg every 8 h 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

q 12 h

q 8 h

q 12 h

q 8 h

q 12 h

For meningitis, q 8–12 h

q 8 h

For meningitis, q 6–8 h

Often a first-line therapy for neonatal meningitis

Ceftazidime

IV, IM

50 mg/kg

q 12 h

q 8 h

q 12 h

q 8 h

q 12 h

q 8 h

Penetrates well into inflamed meninges

70–90% of drug excreted unchanged in urine

Ceftriaxone

IV, IM

50 mg/kg

q 24 h

q 24 h

q 24 h

q 24 h

q 24 h

q 24 h

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 Ca-containing solutions

2nd-line drug for meningitis, after the first wk of life (40–50 mg/kg q 12 h or 80–100 mg/kg q 24 h)

Chloramphenicol

IV

25 mg/kg

q 24 h

q 24 h

q 24 h

q 12–24 h

q 24 h

q 12 h

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

Clindamycin

IV, IM

5 mg/kg

q 12 h

q 12 h

q 12 h

q 8 h

q 8 h

q 6 h

For anaerobes and gram-positive cocci (not enterococci)

Gentamicin*/tobramycin

IV, IM

4–5 mg/kg

q 48 h

q 24–48 h

q 36 h

q 24–48 h

q 24 h

q 12–24 h

Monitoring of serum drug levels required (peak = 5–12 μg/mL; trough = < 2 μg/mL)

Dose reduction required for impaired renal function

Meropenem

IV

20–40 mg/kg

q 12 h

q 8 h

q 12 h

q 8 h

q 8 h

q 8 h

Higher doses used for meningitis

Metronidazole

IV

15 mg/kg

(7.5 mg/kg for neonates ≤ 7 days and < 1200 g)

q 24–48 h

q 24–48 h

q 24 h

q 24 h

q 24 h

q 12 h

Limited data

Loading dose of 15 mg/kg, then a subsequent dose 48 h later in preterm infants

Nafcillin/oxacillin

For meningitis or endocarditis

IV

50 mg/kg

q 12 h

q 12 h

q 12 h

q 8 h

q 8 h

q 6 h

Monitoring of CBC and liver function 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

q 12 h

q 8–12 h

q 12 h

q 8 h

q 8 h

q 6 h

Oxacillin (see Nafcillin/oxacillin)

Penicillin G, aqueous

For meningitis

IV

50,000–75,000 units/kg

q 12 h

q 12 h

q 12 h

q 8 h

q 8 h

q 6 h

Maximum for group B streptococcal meningitis = 450,000 units/kg/day

For most other diseases

IV, IM

25,000 units/kg

q 12 h

q 12 h

q 12 h

q 8 h

q 8 h

q 6 h

Penicillin G, procaine

IM

50,000 units/kg

Not recommended

Not recommended

q 24 h

q 24 h

q 24 h

q 24 h

C aution : Sterile abscess and procaine toxicity

Piperacillin/tazobactam

IV (dose based on piperacillin component)

100 mg/kg

q 12 h

q 8 h

q 12 h

q 8 h

q 12 h

q 8 h

May be increased to 100 mg/kg q 6 h in infants > 28 days

Tobramycin (see Gentamicin/tobramycin)

Dosing based on gestational age and serum creatinine (see Vancomycin Dosage for Neonates)

*Sample should be obtained 30 min after a 30-min IV infusion.

The need to administer a test dose of amphotericin B is controversial.

Cefazolin does not cross the blood-brain barrier.

Vancomycin Dosage for Neonates

Serum Creatinine (mg/dL)

Dose* (IV)

Interval of Administration

≤ 28 wk Gestation

> 28 wk Gestation

< 0.5

< 0.7

15 mg/kg

q 12 h

0.5–0.7

0.7–0.9

20 mg/kg

q 24 h

0.8–1

1–1.2

15 mg/kg

q 24 h

1.1–1.4

1.3–1.6

10 mg/kg

q 24 h

> 1.4

> 1.6

15 mg/kg

q 48 h

*Dose is given by slow IV infusion, over at least 60 min. Monitoring of serum trough level is recommended (trough = 10–15 μg/mL).

Recommended Dosages of Selected Oral Antibiotics for Neonates*

Antibiotic

Dosage

Interval

Comments

Amoxicillin

10–15 mg/kg

q 12 h

Limited data

Azithromycin

5–10 mg/kg

q 24 h

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

Clindamycin

5 mg/kg

q 6–12 h

Limited data

Erythromycin ethylsuccinate

10–12.5 mg/kg

q 6–12 h

For chlamydial infections or pertussis in neonates > 1 mo

Associated with idiopathic hypertrophic pyloric stenosis

Fluconazole

3–12 mg/kg

q 24–72 h

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

Flucytosine

12.5–37.5 mg/kg

q 6 h

Limited data

Used only with amphotericin B to slow emergence of resistance

Monitoring of levels recommended

For neonates < 2000 g and < 7 days, 25 mg/kg q 8 h

Linezolid

10 mg/kg

q 8–12 h

Can be given IV or orally

Used for resistant gram-positive infections

Rifampin

10 mg/kg

q 24 h

For TB

5 mg/kg

q 12 h

For meningococcus prophylaxis, given for 2 days

10 mg/kg

q 24 h

For Haemophilus influenzae prophylaxis, given for 4 days

*Unless otherwise stated, doses are for neonates who are > 7 days and > 2000 g.

The dose for neonates who are < 7 days and < 2000 g is 5 mg/kg q 12 h.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • No US brand name
  • BACTOCILL IN PLASTIC CONTAINER
  • ERY-TAB, ERYTHROCIN
  • MAXIPIME
  • FORTAZ, TAZICEF
  • RIFADIN, RIMACTANE
  • ROCEPHIN
  • GENOPTIC
  • FLAGYL
  • ZITHROMAX
  • VANCOCIN
  • DIFLUCAN
  • MERREM
  • NALLPEN IN PLASTIC CONTAINER
  • AMOXIL
  • CLAFORAN
  • CLEOCIN
  • ANCEF, KEFZOL
  • TOBI, TOBREX
  • ZYVOX
  • ANCOBON
  • AZACTAM

* This is a professional Version *