Penicillin hypersensitivity regimens for prosthetic valve endocarditis

For adults and children with prosthetic valve endocarditis caused by viridans streptococci or S. bovis group with penicillin MIC greater than 0.125 mg/L and less than or equal to 0.5 mg/L who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, if the isolate is susceptible to ceftriaxone (depending on the MIC – seek expert advice), use:

ceftriaxone 2 g (child 1 month or older: 100 mg/kg up to 4 g) intravenously, daily for 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 2 g) intravenously, 12-hourly1 ceftriaxone ceftriaxone ceftriaxone

PLUS

gentamicin (adult and child) 1 mg/kg intravenously, 8-hourly for 2 weeks (monitor plasma concentration; see Principles of aminoglycoside use)2. gentamicin gentamicin gentamicin

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 streptococcal endocarditis who have septic shock or require intensive care support, a modified dosage of ceftriaxone 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 ceftriaxone (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 with prosthetic valve endocarditis who have had a severe immediate3 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:

For adults and children with prosthetic valve endocarditis who have had a severe delayed4 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

PLUS

gentamicin (adult and child) 1 mg/kg intravenously, 8-hourly for 2 weeks (monitor plasma concentration; see Principles of aminoglycoside use)2. gentamicin gentamicin gentamicin

1 Few data are available to guide ceftriaxone dosing recommendations for children with streptococcal endocarditis. The current dosing recommendations are based on the consensus advice of the Antibiotic Expert Group.Return
2 For adults with obesity (body mass index 30 kg/m2 or more), use lean body weight to calculate the dose. For children with obesity, use adjusted body weight to calculate the dose.Return
3 Severe immediate hypersensitivity reactions include anaphylaxis, compromised airway, airway angioedema, hypotension, and collapse.Return
4 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