Penicillin hypersensitivity regimens for community-acquired septic shock in children 2 months or older

In children 2 months or older with community-acquired septic shock of unknown source who report hypersensitivity to penicillins, antibiotic choice depends on the type of hypersensitivity reaction, and whether toxic shock is suspected, 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 immediate 1 hypersensitivity reaction to a penicillin
  • have had a severe delayed2 hypersensitivity reaction to a penicillin
  • are suspected to have toxic shock syndrome – add on therapy
  • 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 septic shock of unknown source 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 septic shock of unknown source 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 septic shock of unknown source who have had 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, as a 3-drug regimen, use:

1gentamicin 7 mg/kg intravenously as an initial dose3; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing gentamicin

OR

1tobramycin 7 mg/kg intravenously as an initial dose3; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing tobramycin

PLUS

ciprofloxacin 10 mg/kg up to 400 mg intravenously, 8-hourly4 ciprofloxacin

PLUS

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

Prioritise administration of gentamicin or tobramycin, because ciprofloxacin and vancomycin require slow infusion.

For children 2 months or older in whom toxic shock syndrome is suspected5, add to the above regimen:

clindamycin 15 mg/kg up to 600 mg intravenously, 8-hourly for a minimum of 72 hours and until organ function has significantly improved6 clindamycin

PLUS

intravenous immunoglobulin (IVIg) 2 g/kg intravenously, as a single dose as soon as possible but not later than 72 hours. It is reasonable to give the dose in divided doses if it is not possible to give a single dose.

If meningitis is suspected, add to the above regimens:

dexamethasone 0.15 mg/kg up to 10 mg intravenously, preferably starting before the first dose of antibiotic, then 6-hourly7. 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-hourly89 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:

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 For children with obesity, use adjusted body weight to calculate the dose.Return
4 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
5 In children, signs of toxic shock syndrome include fever, hypotension, rash and evidence of organ dysfunction. For more information, see Streptococcal toxic shock syndrome.Return
6 There are more clinical and microbiological data to support the use of clindamycin than lincomycin. Intravenous lincomycin can be used at the same dosage if clindamycin is unavailable or if a local protocol recommends its use.Return
7 If dexamethasone is not available, hydrocortisone (4 mg/kg up to 200 mg intravenously) may be used for the initial dose.Return
8 Use the online calculator to determine body surface area.Return
9 Aciclovir dosing in obesity is poorly defined; however, limited data support dosing based on ideal body weight in children.Return