Penicillin hypersensitivity regimens for community-acquired septic shock in adults
In adults 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 syndrome or infection with Neisseria meningitidis is suspected. Regimens are included below for adults 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 toxic shock syndrome – add on therapy.
For adults with community-acquired septic shock of unknown source who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, as a 4-drug regimen, useLegg, 2023:
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
cefazolin 2 g intravenously, 6-hourly. For dosage adjustment in adults with kidney impairment, see cefazolin dosage adjustment cefazolin cefazolin cefazolin
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
PLUS
ceftriaxone 2 g intravenously, 12-hourly3. ceftriaxone ceftriaxone ceftriaxone
If there is a low suspicion of infection with N. meningitidis, ceftriaxone may be discontinued – seek expert advice.
For adults with community-acquired septic shock who have had a severe immediate1 hypersensitivity reaction to a penicillin, the above cephalosporin-containing 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 who have had a severe immediate1 hypersensitivity reaction to a penicillin in whom a cephalosporin is not used, or for adults who have had a severe delayed2 hypersensitivity reaction to a penicillin, as a 3-drug regimen useLegg, 2023:
1gentamicin intravenously; see Gentamicin initial dose calculator for adults for initial dose. See Principles of aminoglycoside use for prescribing considerations and subsequent dosing gentamicin gentamicingentamicin
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
PLUS
ciprofloxacin 400 mg intravenously, 8-hourly4. For dosage adjustment in adults with kidney impairment, see ciprofloxacin intravenous dosage adjustment. ciprofloxacin ciprofloxacin ciprofloxacin
If there is a low suspicion of infection with N. meningitidis, ciprofloxacin may be discontinued – seek expert advice.
For adults in whom toxic shock syndrome is suspected5, add to either of the regimens above:
clindamycin 600 mg intravenously, 8-hourly for a minimum of 72 hours and until organ function has significantly improved6 clindamycin clindamycin 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. intravenous immunoglobulin (IVIg)
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.