Penicillin hypersensitivity regimens for hospital-acquired sepsis without septic shock in adults

In adults with hospital-acquired sepsis of unknown source without septic shock who report penicillin hypersensitivity, antibiotic choice depends on the type of hypersensitivity reaction and whether methicillin-resistant Staphylococcus aureus (MRSA) is suspected. Regimens are included below for adults who have had a:

  • nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin
  • severe immediate1 hypersensitivity reaction to a penicillin
  • severe delayed2 hypersensitivity reaction to a penicillin.

For adults at risk of invasive Candida infection, also consider the addition of an antifungal.

For adults with hospital-acquired sepsis of unknown source without septic shock who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, use:

cefepime 2 g intravenously, 8-hourly3. For dosage adjustment in adults with kidney impairment, see cefepime dosage adjustment cefepime cefepime cefepime

PLUS if the patient has suspected line-related sepsis, the hospital has a significant rate of nosocomial MRSA infection, or the patient has other risk factors for MRSA infection

vancomycin 25 mg/kg (actual body weight) rounded up to nearest 125 mg, up to 3 g intravenously, as a loading dose. See Calculated vancomycin loading dosage in critically ill adults for calculated weight-based loading doses. Subsequent doses are dependent on weight and kidney function; see Intermittent vancomycin dosing for critically ill adults. vancomycin vancomycin vancomycin

For adults with hospital-acquired sepsis of unknown source without septic shock who have had a severe immediate1 hypersensitivity reaction to a penicillin, the above cefepime-based 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 adults with hospital-acquired sepsis of unknown source without septic shock who have had a severe immediate1 hypersensitivity reaction to a penicillin in whom the cefepime-based regimen is not used, or for patients who have had a severe delayed2 hypersensitivity reaction to a penicillin, as a 2-drug regimen, use:

1gentamicin intravenously; see Gentamicin initial dose calculator for adults for initial dose. See Principles of aminoglycoside use for prescribing considerations and subsequent dosing gentamicin gentamicin gentamicin

OR

1tobramycin intravenously; see Tobramycin initial dose calculator for adults for initial dose. See Principles of aminoglycoside use for prescribing considerations and subsequent dosing tobramycin tobramycin tobramycin

PLUS

vancomycin 25 mg/kg (actual body weight) rounded up to nearest 125 mg, up to 3 g intravenously, as a loading dose. See Calculated vancomycin loading dosage in critically ill adults for calculated weight-based loading doses. Subsequent doses are dependent on weight and kidney function; see Intermittent vancomycin dosing for critically ill adults. vancomycin vancomycin vancomycin

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 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 In patients 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 requiring intensive care support.Return