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

For children 2 months or older with hospital-acquired sepsis or septic shock of unknown source who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, use:

cefepime 50 mg/kg up to 2 g intravenously, 8-hourly1 cefepime

PLUS if the child has septic shock, suspected line-related sepsis or other risk of MRSA infection

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

Systematic reviews suggest that adding an aminoglycoside to the empirical regimen for hospital-acquired sepsis or septic shock is associated with increased toxicity without additional clinical benefit. However, for patients with septic shock, adding an aminoglycoside may be appropriate if there is suspicion of infection with gram-negative organisms resistant to piperacillin+tazobactam. This practice is most useful if local microbiological data show a significant proportion of gram-negative organisms are susceptible to aminoglycosidesDickinson, 2011.

For children 2 months or older with hospital-acquired sepsis or septic shock of unknown source who have had a severe immediate2 hypersensitivity reaction to a penicillin, the cefepime-based regimen above 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 hospital-acquired sepsis or septic shock who have had a severe immediate2 hypersensitivity reaction to a penicillin in whom the cefepime-based regimen is not used, or who have had a severe delayed3 hypersensitivity reaction to a penicillin, as a 2-drug regimen, use:

1gentamicin 7 mg/kg intravenously for initial dose4; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing gentamicin

OR

1tobramycin 7 mg/kg intravenously for initial dose4; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing tobramycin

PLUS

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

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

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.

For children at risk of invasive Candida infection, consider the addition of an empirical antifungal.

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.

1 In patients with septic shock or requiring intensive care support, there is a theoretical benefit from administering the intermittent dose of cefepime over 3 to 4 hours, or administering the daily dose over 24 hours. However, at the time of writing, there are inadequate data to recommend administration over 3 hours or longer for patients with septic shock or requiring intensive care support.Return
2 Severe immediate hypersensitivity reactions include anaphylaxis, compromised airway, airway angioedema, hypotension and collapse.Return
3 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
4 For children with obesity, use adjusted body weight to calculate the dose.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