Neonatal sepsis

Question:  What antibiotics should be given for a newborn with suspected septic shock?

Ampicillin PLUS gentamicin OR cefotaxime (from Tintinalli)

The main organisms to be concerned about are gram-positives (mainly Group B strep, also Listeria) and gram-negatives (E. coli).  Ampicillin, an extended-spectrum penicillin, covers group B strep and Listeria, while gentamicin, an aminoglycoside, provides coverage for gram negative organisms.  If gram negative meningitis is suspected, cefotaxime is favored for its better CNS penetration.

More on neonatal sepsis:
In the critically ill neonate, the diagnosis of sepsis should always be considered.  In the ED setting, it is not always possible to distinguish the various causes of the neonate in distress--septic shock, cardiogenic shock from congenital heart disease, inborn errors of metabolism, etc.  Therefore empiric treatment for septic shock should be initiated in the critically ill newborn, as early treatment of sepsis has been shown to improve outcomes.

Early-onset sepsis
Early-onset sepsis (within first few days of life) is typically due to infection acquired from the mother, either transplacentally, transcervically, or via contact with microbe during passage through a colonized birth canal.  Organisms responsible for early-onset sepsis include:

1.  Group B Strep
2.  E. coli
3.  Coagulase negative staph
4.  Haemophilus influenzae
5.  Listeria monocytogenes


Risk factors for early-onset neonatal sepsis include maternal GBS colonization (though incidence of GBS infection has been reduced due to third-trimester screening programs), premature rupture of membranes, prolonged rupture of membranes, preterm rupture of membranes, chorioamnionitis, prematurity, and maternal UTI.

Workup for the neonate with suspected sepsis includes CBC with differential, blood cultures, CSF gram stain and culture, chest xray, urine studies, and possibly CRP or other infection markers.  Hemodynamic support should be provided with IV fluids and pressors, if indicated.  Antibiotics should be started empirically to cover for gram positive organisms (especially group B strep), and gram-negative organisms (namely E. coli).  For infants < 1 week of age, Tintinalli recommends ampicillin PLUS gentamicin OR cefotaxime.

A 2009 Cochrane review sought to compare the efficacy of different antibiotic regimens for neonatal sepsis, and found that there was no evidence to recommend one particular regimen over another.  This was largely due to small sample size (only 2 studies comparing treatment of sepsis in infants < 48 hours old).

Late-onset sepsis

Late-onset sepsis (between 4-90 days of life) is more likely due to organisms acquired from the caregiving environment (including hospital-acquired infections).  While pneumonia is more common in early-onset sepsis, meningitis and bacteremia are more common in late-onset sepsis.  Organisms include:

1.  Coagulase negative staph

2.  Staph aureus

3.  E. coli

4.  Klebsiella

5.  Pseudomonas

6.  Group B strep

7.  Strep pneumoniae

For infants age 1-4 weeks, Tintinalli recommends ampicillin PLUS cefotaxime/ceftiaxone.  This covers for gram positive and gram negative organisms.


References:
1.  From Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7th Ed. Tintinalli, JE, Ed, et al.  New York: McGraw Hill, 2011: p. 74, 1012.


2.  Cochrane review.  Antibiotics regimens for suspected early neonatal sepsis.  Published online 21 Jan 2009. Available at http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004495.pub2/abstract.  Accessed Jan 7. 2012.