Penicillin hypersensitivity regimens for prosthetic valve endocarditis caused by methicillin-susceptible staphylococci

For prosthetic valve endocarditis caused by methicillin-susceptible staphylococci in adults and children who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, use:

cefazolin 2 g (child: 50 mg/kg up to 2 g) intravenously, 8-hourly for 6 weeks. For patients with septic shock or requiring intensive care support, use 6-hourly dosing. For dosage adjustment in adults with kidney impairment, see cefazolin dosage adjustment. cefazolin cefazolin cefazolin

Pharmacokinetics may be altered in patients who are critically ill (eg because of enhanced kidney clearance or changes in volume of distribution). To ensure adequate drug exposure in patients with staphylococcal endocarditis who have septic shock or require intensive care support, a modified dosage of cefazolin is recommended. Once the critical illness has resolved, consider switching to the standard dosage. If the isolate is not reported to have dose-dependent susceptibility to cefazolin (ie susceptible dose dependent [SDD] or susceptible increased exposure [I or SIE]), it may also be appropriate to switch to the standard dose – seek expert advice.

Some staphylococcal strains exhibit an ‘inoculum effect’, meaning that they have resistance to cefazolin at high inocula. This effect is due, at least in part, to hydrolysis of cefazolin by staphylococcal penicillinase and may be associated with clinical treatment failure. Importantly, this pathogen phenotype can be difficult to accurately identify in many microbiology laboratories. If using cefazolin, monitor closely for lack of efficacy or treatment failure, especially when infection burden is high or source control has not been fully achieved – seek expert adviceChambers, 2020 Miller, 2018 Nannini, 2009.

For patients who have had severe immediate¹ hypersensitivity reaction to a penicillin, several treatment options are available – seek expert advice. Options that an infectious diseases physician or clinical microbiologist may use include:

using cefazolin (see dosage above) – this can be considered if a beta-lactam antibiotic is strongly preferred (eg in a critical situation); for considerations, see Severe immediate hypersensitivity: Implications of cross-reactivity between penicillins and cephalosporins
performing desensitisation
using vancomycin (see dosage below).

For patients who have had a severe delayed² hypersensitivity reaction to a penicillin, use:

vancomycin intravenously for 6 weeks; for initial dosing, see Intermittent vancomycin dosing for noncritically ill adults or Intermittent vancomycin dosing for young infants and children. vancomycin vancomycin vancomycin

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