What is the recommended empirical antibiotic therapy for a febrile (feverish) five-week-old infant?

From the Guidelines

The recommended empirical antibiotic therapy for a febrile five-week-old infant is ampicillin IV or IM (150 mg/kg per day divided every 8 hours) and either ceftazidime IV or IM (150 mg/kg per day divided every 8 hours) or gentamicin IV or IM (4 mg/kg per dose every 24 hours). This combination provides broad-spectrum coverage against the most common pathogens in this age group, including Group B Streptococcus, Escherichia coli, Listeria monocytogenes, and other gram-negative bacteria 1.

Key Considerations

• A full sepsis workup should be performed before starting antibiotics, including blood culture, urine culture, and often cerebrospinal fluid analysis through lumbar puncture, as meningitis is a significant concern in this age group.
• Hospitalization is necessary for these infants due to their high risk of serious bacterial infection and limited ability to localize infection.
• Treatment typically continues for at least 48-72 hours while awaiting culture results, with total duration determined by the specific infection identified.
• The use of a local antibiogram, if available, can guide choices and ensure the most effective treatment regimen is used 1.

Pathogen Coverage

• The recommended regimen provides coverage against common pathogens, including:

• Group B Streptococcus
• Escherichia coli
• Listeria monocytogenes
• Other gram-negative bacteria

• The addition of gentamicin may provide clinical benefit due to synergy with ampicillin against Group B Streptococcus and enterococcal species 1.

Alternative Regimens

• For infants with a suspected urinary tract infection, ampicillin IV or IM (150 mg/kg per day divided every 8 hours) and either ceftazidime IV or IM (150 mg/kg per day divided every 8 hours) or gentamicin IV or IM (4 mg/kg per dose every 24 hours) may be used 1.
• For infants with suspected bacterial meningitis, ampicillin IV or IM (300 mg/kg per day divided every 6 hours) and ceftazidime IV or IM (150 mg/kg per day divided every 8 hours) may be used 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 a febrile five-week-old infant may include gentamicin in combination with a penicillin-type drug, as it has been shown to be effective in bacterial neonatal sepsis and serious bacterial infections 2.

• Gentamicin may be used as initial therapy in suspected or confirmed gram-negative infections.
• A penicillin-type drug is usually indicated as concomitant therapy with gentamicin in the neonate with suspected bacterial sepsis or staphylococcal pneumonia.

From the Research

Empirical Antibiotic Therapy for Febrile Infants

The recommended empirical antibiotic therapy for a febrile five-week-old infant is a topic of interest in pediatric care.

• The combination of ampicillin and gentamicin is a commonly recommended regimen for empirical treatment of febrile infants aged 90 days or younger, as it provides appropriate antibiotic coverage for the most common causative pathogens, including Escherichia coli and group B Streptococcus 3, 4.
• A study published in 2015 found that ampicillin and gentamicin would have provided effective coverage for 98.5% of infants with serious bacterial infections, and unnecessarily broad therapy for 4.3% 3.
• Another study published in 2023 noted that ampicillin plus gentamicin remains the recommended antibiotic regimen for early onset neonatal sepsis, despite concerns about resistance and long-term safety 5.
• However, some studies suggest that the addition of a third-generation cephalosporin may be necessary in certain cases, such as suspected meningitis or in areas with high rates of resistance to ampicillin and gentamicin 3, 6.
• A case study published in 2009 highlighted the importance of considering risk factors for resistant bacterial infections in young, ill-appearing infants, and suggested that empirical antibiotic treatment may need to be broader than recommended by current guidelines in some cases 7.

Antibiotic Regimens

Some common antibiotic regimens used to treat febrile infants include:

• Ampicillin and gentamicin: a traditional combination that provides broad coverage for Gram-negative and Gram-positive bacteria 3, 4.
• Third-generation cephalosporin: may be added to ampicillin and gentamicin in cases of suspected meningitis or in areas with high rates of resistance 3, 6.
• Ampicillin plus a third-generation cephalosporin: may provide improved coverage for certain pathogens, but may also increase the risk of unnecessarily broad therapy 6.

Considerations

When selecting an empirical antibiotic regimen for a febrile infant, it is essential to consider the local epidemiology of bacterial infections, the risk of resistance, and the potential for unnecessarily broad therapy 3, 6, 4.