Penicillin hypersensitivity regimens for endocarditis caused by the HACEK group
For adults and children with native and prosthetic valve endocarditis caused by HACEK group strains who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, use:
1ceftriaxone 2 g (child 1 month or older: 50 mg/kg up to 2 g) intravenously, daily for 4 to 6 weeks. For patients with septic shock or requiring intensive care support, use 1 g (child 1 month or older: 50 mg/kg up to 1 g) intravenously, 12-hourly ceftriaxone ceftriaxone ceftriaxone
OR
1cefotaxime 2 g (child: 50 mg/kg up to 2 g) intravenously, 8-hourly for 4 to 6 weeks. For patients with septic shock or requiring intensive care support, use 2 g (child: 50 mg/kg up to 2 g) intravenously, 6-hourly. For dosage adjustment in adults with kidney impairment, see cefotaxime dosage adjustment. cefotaxime cefotaxime cefotaxime
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 endocarditis caused by the HACEK group who have septic shock or require intensive care support, modified dosages of ceftriaxone and cefotaxime are 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 ceftriaxone or cefotaxime (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.
For patients who have had a 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 ceftriaxone or cefotaxime – 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
- alternative parenteral therapy if neither a cephalosporin nor desensitisation is appropriate.
For patients who have had a severe delayed2 hypersensitivity reaction to a penicillin, seek expert advice.
Duration of therapy for native valve endocarditis is usually 4 weeks. Prosthetic valve endocarditis requires 6 weeks of therapy, and surgery is often required.
For complicated cases of native valve or prosthetic valve endocarditis, the addition of gentamicin is sometimes required for synergy in the first 2 weeks – seek expert advice.