Penicillin hypersensitivity regimens for community-acquired sepsis without septic shock in children 2 months or older

In children 2 months or older with community-acquired sepsis of unknown source without septic shock who report hypersensitivity to penicillins, treatment choice depends on the type of hypersensitivity reaction, and whether meningitis has been excluded, herpes simplex encephalitis is suspected, and intravenous (or intraosseous) access has been established. Regimens are included below for children 2 months or older who:

have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin
have had a severe immediate¹ hypersensitivity reaction to a penicillin
have had a severe delayed² hypersensitivity reaction to a penicillin
are suspected to have meningitis – add on therapy
are suspected to have herpes simplex encephalitis – add on therapy
do not have intravenous (or intraosseous) access.

For children 2 months or older with community-acquired sepsis of unknown source without septic shock who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, the standard empirical regimen is suitable.

For children 2 months or older with community-acquired sepsis of unknown source without septic shock who have had a severe immediate¹ hypersensitivity reaction to a penicillin, the standard empirical regimen can be considered if a beta-lactam antibiotic is strongly preferred (for considerations, see Severe immediate hypersensitivity: Implications of cross-reactivity between penicillins and cephalosporins).

For children 2 months or older with community-acquired sepsis of unknown source without septic shock who have had a severe immediate¹ hypersensitivity reaction to a penicillin in whom the standard empirical regimen is not used, or who have had a severe delayed² hypersensitivity reaction to a penicillin, use:

ciprofloxacin 10 mg/kg up to 400 mg intravenously, 8-hourly³ ciprofloxacin

PLUS

vancomycin intravenously; for initial dosing, see Intermittent vancomycin dosing for young infants and children. vancomycin

If meningitis is suspected, add to the above regimen:

dexamethasone 0.15 mg/kg up to 10 mg intravenously, preferably starting before the first dose of antibiotic, then 6-hourly⁴. For duration of therapy, see Overview of empirical therapy for adults and children 2 months or older with meningitis. dexamethasone

If herpes simplex encephalitis is suspected, add to the above regimens:

aciclovir intravenously, 8-hourly⁵ ⁶ aciclovir

child younger than 5 years: 20 mg/kg or 500 mg/m²

child 5 years to 12 years: 15 mg/kg or 500 mg/m²

child older than 12 years: 10 mg/kg.

If herpes simplex encephalitis is confirmed, seek expert advice. See also Herpes simplex encephalitis for subsequent management.

These empirical regimens are intended for initial therapy only (up to 48 hours). Modify therapy as soon as additional information is available (eg source of infection, results of Gram stain, culture and susceptibility testing). Evaluate the appropriateness of antimicrobial therapy daily, with consideration given to the patient’s clinical status and the principles of antimicrobial stewardship.

If intravenous (or intraosseous) access cannot be rapidly established (eg within 15 minutes) in children 2 months or older who report hypersensitivity to penicillins, use the following approach:

severe immediate¹ hypersensitivity reaction to a penicillin – the standard empirical intramuscular regimen can be considered if a beta-lactam antibiotic is strongly preferred (for considerations, see Severe immediate hypersensitivity: Implications of cross-reactivity between penicillins and cephalosporins)
severe immediate¹ hypersensitivity reaction to a penicillin in whom the standard empirical intramuscular regimen is not used, or who have had a severe delayed² hypersensitivity reaction to a penicillin – seek expert advice.

¹ Severe immediate hypersensitivity reactions include anaphylaxis, compromised airway, airway angioedema, hypotension and collapse.Return

² Severe delayed hypersensitivity reactions include cutaneous adverse drug reactions (eg drug rash with eosinophilia and systemic symptoms [DRESS], Stevens–Johnson syndrome/toxic epidermal necrolysis [SJS/TEN], severe blistering or desquamative rash), and significant internal organ involvement (eg acute interstitial nephritis).Return

³ Ciprofloxacin is not licensed for use in children on the basis of animal studies that showed an adverse effect on cartilage development with quinolone use; however, clinical trial data suggest that adverse musculoskeletal events are usually mild and short term, similar to those observed in adults. Ciprofloxacin can be used in children when it is the drug of choice.Return

⁴ If dexamethasone is not available, hydrocortisone (4 mg/kg up to 200 mg intravenously) may be used for the initial dose.Return

⁵ Use the online calculator to determine body surface area.Return

⁶ Aciclovir dosing in obesity is poorly defined; however, limited data support dosing based on ideal body weight in children.Return