Safety Criteria for Ceftriaxone Administration to Neonates

Patient Population: Pediatric

Cefotaxime, historically the preferred 3rd generation cephalosporin for neonates, is no longer manufactured.  

  • Ceftazidime is an alternative, however, it is broader in spectrum with antipseudomonal activity and increased use may impact gut microbiota and contribute to antibiotic resistance.  
  • Ceftriaxone may be considered in neonates without contraindications: 
    • Avoid use in neonates receiving IV calcium-containing solutions due to reports of death and serious adverse events with calcium-ceftriaxone deposits in neonatal vasculature with concomitant use. This is a potential risk regardless of route of administration even if ceftriaxone is given intramuscularly.  
    • Avoid use in neonates with hyperbilirubinemia due to potential for displacement of bilirubin from albumin with theoretical potential for kernicterus or bilirubin encephalopathy.   
Neonatal Candidates - to receive Ceftriaxone  
(must meet ALL criteria) 
Contraindications to neonate receiving Ceftriaxone (if meets ANY criteria)*
  • Postnatal age >= 14 days AND 
  • Corrected gestational age >= 41 weeks AND 
  • Total bilirubin <= 5 mg/dL AND 
  • Will not receive IV calcium-containing solutions within 48 hours of Ceftriaxone AND 
  • Has not received IV calcium-containing solutions within 48 hours prior to Ceftriaxone  
  • Unconjugated hyperbilirubinemia OR 
  • Receipt of any IV calcium-containing solutions within 48 hours of Ceftriaxone OR 
  • Critical illness (acidosis, hypotension, etc.)  
  • Due to possibility of requiring IV calcium administration 
  • Patients with acute hypocalcemia who may require IV calcium administration 

Administration of a single dose of Ceftriaxone to neonates with ophthalmia neonatorum suspected or confirmed to be caused by Neisseria gonorrhoeae is an exception to most contraindications listed above, including hyperbilirubinemia, with the following precautions:  

  • Intravenous calcium-containing solutions should not be given within 48 hours before or after the Ceftriaxone dose.  
  • Evaluate and treat hyperbilirubinemia per usual clinical practice. Monitor for hyperbilirubinemia following ceftriaxone therapy.  

*Note these contraindications apply specifically to neonates but not to older infants (>44 weeks corrected gestational age) or children 

Neonatal Ceftriaxone Dose 

Non-Meningitis (postnatal age >=14 days): 50 mg/kg IV q24h 

Meningitis (postnatal age >=14 days): 100 mg/kg IV loading dose on day 1, then 80 mg/kg IV q24h  starting day 2 

Ophthalmia NeonatorumRefer to guidelines 

See further CAP management guidelines from the UCSF Northern California Pediatric Hospital Medicine Consortium, though reference below recommendations for updated antibiotic selection. 

At BCH OAK follow site-specific CAP algorithm (link requires password log in to Box); recommendations provided below are compatible with BCH OAK CAP algorithm, but the algorithm provides additional details in pathway form.   


Workowski KA, et al. Centers for Disease Control and Prevention. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep 2021;70:1-187.

Hile GB, et al. Occurrence of hyperbilirubinemia in neonates given a short-term course of ceftriaxone versus cefotaxime for sepsis. J Pediatr Pharmacol Ther 2021;26:99-103. 

Pediatric Empiric Antimicrobial Therapy Guidelines

This is a subsection of the UCSF Benioff Children’s Hospitals Empiric Antimicrobial Therapy Guidelines, developed by the Pediatric Antimicrobial Stewardship Programs at each campus to inform initial selection of empiric antimicrobial therapy for children at the UCSF Benioff Children’s Hospitals and affiliated outpatient sites. 

These are guidelines only and not intended to replace clinical judgment. Modification of therapy may be indicated based on patient comorbidities, previous antibiotic therapy or infection history. Doses provided are usual doses but may require modification based on patient age or comorbid conditions. Refer to Pediatric Antimicrobial Dosing Guideline for further guidance on dosing in children, and Neonatal Dosing Guideline for infants < 1 month of age. Consult a pediatric pharmacist for individualized renal or hepatic dose adjustment. Durations provided are usual recommendations for patients who are responding appropriately to therapy. For additional guidance, please contact Pediatric Infectious Diseases (ID) or the Pediatric Antimicrobial Stewardship Program (ASP) at the campus where your patient is receiving care.  

For questions or feedback about these guidelines, please email primary content owners, Rachel Wattier, Pediatric ASP Medical Director at BCH SF and Prachi Singh, Pediatric ASP Medical Director at BCH OAK. 

The content of these guidelines was updated in July 2021. See Summary and Rationale for Changes (password login to Box needed) for detailed explanations of the content changes.