What is the recommended empirical antibiotic therapy for neonatal fever?

From the Guidelines

The recommended empirical antibiotic therapy for neonatal fever is ampicillin plus gentamicin or a third-generation cephalosporin such as cefotaxime, with the specific regimen depending on the age of the neonate and the suspected source of infection, as outlined in the most recent guidelines from the American Academy of Pediatrics 1.

Key Considerations

• For neonates under 28 days old, ampicillin (150 mg/kg per day divided every 8 hours) plus gentamicin (4 mg/kg per dose every 24 hours) is a common first-line regimen, as recommended by the American Academy of Pediatrics 1.
• The choice of antibiotic regimen should be guided by the suspected source of infection, with different regimens recommended for urinary tract infections, bacterial meningitis, and other sources of infection 1.
• In areas with high prevalence of ampicillin-resistant organisms, cefotaxime (50 mg/kg per dose every 24 hours) may be used as an alternative to gentamicin 1.
• Treatment should be initiated immediately after appropriate cultures are obtained, without waiting for results, and the duration of treatment should be based on the clinical response and the results of cultures 1.

Important Pathogens

• Group B Streptococcus, Listeria monocytogenes, and gram-negative organisms like Escherichia coli are common causes of neonatal sepsis, and the chosen antibiotic regimen should provide coverage against these pathogens 1.
• In low- and middle-income countries, there is a high prevalence of multidrug-resistant Gram-negative organisms, which can make treatment more challenging 1.

Special Considerations

• Acyclovir (20 mg/kg IV every 8 hours) should be added if herpes simplex virus infection is suspected, particularly with maternal history of genital herpes, vesicular rash, seizures, or CSF pleocytosis 1.
• The use of local antibiograms can help guide the choice of empirical antibiotic therapy, particularly in areas with high rates of antibiotic resistance 1.

From the FDA Drug Label

Gentamicin Injection, USP is indicated in the treatment of serious infections caused by susceptible strains of the following microorganisms: Pseudomonas aeruginosa, Proteus species (indole-positive and indole-negative), Escherichia coli, Klebsiella-Enterobacter-Serratia species, Citrobacter species and Staphylococcus species (coagulase-positive and coagulase-negative) Clinical studies have shown gentamicin injection to be effective in bacterial neonatal sepsis; bacterial septicemia and serious bacterial infections of the central nervous system (meningitis), urinary tract, respiratory tract, gastrointestinal tract (including peritonitis), skin, bone and soft tissue (including burns) In the neonate with suspected bacterial sepsis or staphylococcal pneumonia, a penicillin-type drug is also usually indicated as concomitant therapy with gentamicin.

The recommended empirical antibiotic therapy for neonatal fever may include gentamicin in combination with a penicillin-type drug, as it has been shown to be effective in bacterial neonatal sepsis and other serious infections 2.

• Gentamicin may be considered as initial therapy in suspected or confirmed gram-negative infections.
• The decision to continue therapy with gentamicin should be based on the results of susceptibility tests, the severity of the infection, and other important considerations.
• It is essential to obtain specimens for bacterial culture to isolate and identify causative organisms and determine their susceptibility to gentamicin.

From the Research

Assessment of Neonatal Fever

The assessment of neonatal fever is crucial in determining the appropriate empirical antibiotic therapy.

Recommended Empirical Antibiotic Therapy

• The recommended empirical antibiotic therapy for neonatal fever includes:
  • Ampicillin and gentamicin 3, 4, 5, 6
  • Ampicillin and cefotaxime 3
  • Ampicillin, an aminoglycoside, and a third-generation cephalosporin 4
• These combinations provide broad-spectrum coverage against common pathogens, including Group B streptococcus, Escherichia coli, and Listeria monocytogenes 3, 4, 6

Considerations for Specific Patient Populations

• For very low birth weight neonates or those with long-term vascular catheters, additional considerations must be taken into account, including the potential for resistant organisms such as enterococci and gentamicin-resistant gram-negative enteric bacilli 3
• In these cases, empiric combinations of antibiotics may include ampicillin or vancomycin, plus amikacin or cefotaxime 3

Important Notes

• The use of ampicillin and cefotaxime has been associated with an increased risk of neonatal death compared to ampicillin and gentamicin 7
• The combination of ampicillin and gentamicin provides appropriate antibiotic coverage for the majority of cases of serious bacterial infections in hospitalized febrile infants aged 90 days or younger 5
• Antimicrobial susceptibility profiles among neonatal early-onset sepsis pathogens suggest that the vast majority of contemporary pathogens are susceptible to the combination of ampicillin and gentamicin 6