Febrile Infant Clinical Pathway — Emergency Department and Inpatient

Antimicrobials: Recommendations, Dosing, and Rationale

Antibiotic selection is based on infant’s age, appearance, HSV risk factors, UA results, inflammatory markers, and CSF results (if LP performed).

Antimicrobial Recommendations by Age

Age	Well-Appearing and no CSF pleocytosis	Ill-Appearing (Sepsis Red) and/or CSF pleocytosis Consider Sepsis N/IICU, Sepsis ED, Inpatient, PICU
0-21 Days	Ampicillin Ceftazidime Acyclovir	Vancomycin Cefepime Acyclovir
22-28 Days	Abnormal UA or IM Ampicillin Ceftazidime Consider acyclovir – see HSV Testing Indications	Vancomycin Cefepime Consider acyclovir – see HSV Testing Indications
29-56 Days	Normal IM, Abnormal UA, meets oral antibiotic criteria Cephalexin Abnormal IM or does not meet oral antibiotic criteria Ceftriaxone Consider acyclovir – see HSV Testing Indications	Vancomycin Ceftriaxone Consider acyclovir – see HSV Testing Indications

Antimicrobial Dosing Recommendations

Antimicrobial	Recommended Dosing by Age, Weight, Dosing Interval
Ampicillin IV	Postnatal age ≤ 7 days 100 mg/kg/dose q8hrs (meningitic dosing) Postnatal age > 7 to 28 days 75 mg/kg/dose q6hrs (meningitic dosing) Postnatal age > 28 days 50 mg/kg/dose q6hrs (UTI dosing)
Ceftazidime IV	Postnatal age ≤ 7 days 50 mg/kg/dose q12hrs Postnatal age > 7 days 50 mg/kg/dose q8hrs
Acyclovir IV	20 mg/kg/dose q8hrs
Cephalexin PO	Postnatal age > 28 days 50 mg/kg/day divided q8hrs Max: 500 mg/dose
Ceftriaxone IV	Ill-appearing and/or CSF pleocytosis postnatal age > 28 days 50 mg/kg/dose q12hrs Well-appearing and no CSF pleocytosis Postnatal age > 28 days 50 mg/kg/dose q24hrs *IV ceftriaxone should not be used in patients ≤ 28 days of age
Cefepime IV	Neonate 50 mg/kg/dose q12hrs Infant 50 mg/kg/dose q8hrs
Vancomycin IV	Postnatal age < 7 days < 1000 g: 15 mg/kg/dose q24hrs 1000-2000 g: 15 mg/kg/dose q18hrs > 2000 g: 15 mg/kg/dose q12hrs
	Postnatal age ≥ 7 days to 28 days < 1000 g: 15 mg/kg/dose q18hrs 1000-2000 g: 15 mg/kg/dose q12hrs > 2000 g: 15 mg/kg/dose q8hrs
	Postnatal age > 28 days: 15 mg/kg/dose q6hrs

Rationale for Antibiotic Choices

Age	Indications/Pathogens	Antibiotics
All Ages	Ill-appearance or Meningitis CSF Pleocytosis CSF Gram Stain positive for organisms Consult ID if gram negative organisms present	Vancomycin Offers coverage for cephalosporin-resistant organisms, e.g. MRSA (methicillin-resistant S. aureus), and for ceftriaxone non-susceptible Streptococcus pneumoniae meningitis Note Vancomycin and ceftriaxone should be used in combination in cases of ceftriaxone non-susceptible S. pneumoniae meningitis Cefepime (0-28 days) Ceftriaxone not recommended in this age group due to: Increased risk of kernicterus due to displacement of bilirubin from albumin Increased risk for hemolysis when used with calcium-containing solutions within 48 hours Cefepime replaces ceftriaxone and offers coverage for: Enterobacterales, including E. coli, H. influenzae Gram-positive organisms including group B Streptococcus, S. pneumoniae MSSA (methicillin-susceptible S. aureus) Ceftriaxone (29-56 days) Offers coverage for Group B streptococcus, S. pneumoniae, Enterobacterales, including E. coli, and H. influenzae
0-28 Days	Enterobacterales (e.g., E. coli) Group B streptococcus S. aureus Listeria monocytogenes (extremely rare) HSV	Ampicillin Provides coverage for Group B streptococcus and Listeria (Listeria is extremely rare) Ceftazidime Provides coverage for Enterobacterales, including E. coli and K. pneumoniae Offers excellent CNS penetration Does not cover methicillin-sensitive S. aureus Ceftriaxone Ceftriaxone not recommended in this age group due to: Increased risk of kernicterus due to displacement of bilirubin from albumin Increased risk for hemolysis when used with calcium-containing solutions within 48 hours
29-56 Days	S. pneumoniae Group B streptococcus E. coli H. influenzae N. meningitidis S. aureus Listeria monocytogenes Other gram negative organisms	Ceftriaxone Offers coverage for Group B streptococcus, S. pneumoniae, community acquired Enterobacterales including E. coli, and H. influenzae Note Ceftriaxone does not cover Enterococcus spp. Cephalexin Offers UTI coverage for E. coli, Group B streptococcus, S. aureus (does not cover Enterococcus)

If you have questions about any of the clinical pathways or about the process of creating a clinical pathway, please contact us.

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The clinical pathways are based upon publicly available medical evidence and/or a consensus of medical practitioners at The Children’s Hospital of Philadelphia (“CHOP”) and are current at the time of publication. These clinical pathways are intended to be a guide for practitioners and may need to be adapted for each specific patient based on the practitioner’s professional judgment, consideration of any unique circumstances, the needs of each patient and their family, and/or the availability of various resources at the health care institution where the patient is located.

Accordingly, these clinical pathways are not intended to constitute medical advice or treatment, or to create a doctor-patient relationship between/among The Children’s Hospital of Philadelphia (“CHOP”), its physicians and the individual patients in question. CHOP does not represent or warrant that the clinical pathways are in every respect accurate or complete, or that one or more of them apply to a particular patient or medical condition. CHOP is not responsible for any errors or omissions in the clinical pathways, or for any outcomes a patient might experience where a clinician consulted one or more such pathways in connection with providing care for that patient.

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Febrile Infant Clinical Pathway — Emergency Department and Inpatient

Antimicrobials: Recommendations, Dosing, and Rationale

Antimicrobial Recommendations by Age

Antimicrobial Dosing Recommendations

Rationale for Antibiotic Choices

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Febrile Infant — Antimicrobials: Recommendations, Dosing, and Rationale — Clinical Pathway: Emergency Department and Inpatient

Febrile Infant Clinical Pathway — Emergency Department and Inpatient

Antimicrobials: Recommendations, Dosing, and Rationale

Antimicrobial Recommendations by Age

Antimicrobial Dosing Recommendations

Rationale for Antibiotic Choices