Penicillin hypersensitivity regimens for native valve endocarditis

For adults and children with uncomplicated or complicated native valve endocarditis caused by viridans streptococci or S. bovis group with penicillin MIC 0.125 mg/L or lower who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, use:

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

Alternatively, for adults with uncomplicated native valve endocarditis who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, use:

ceftriaxone 2 g intravenously, daily for 2 weeks. For adults with septic shock or requiring intensive care support, use 1 g intravenously, 12-hourly¹ ceftriaxone ceftriaxone ceftriaxone

PLUS

gentamicin 1 mg/kg intravenously, 8-hourly for 2 weeks (monitor plasma concentration; see Principles of aminoglycoside use)³. gentamicin gentamicin gentamicin

For patients with uncomplicated or complicated native valve endocarditis who have had a severe immediate⁴ 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 a ceftriaxone-containing regimen (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 adults and children with uncomplicated or complicated native valve endocarditis who have had a severe delayed⁵ hypersensitivity reaction to a penicillin, use:

vancomycin intravenously for 4 weeks; for initial dosing, see Intermittent vancomycin dosing for noncritically ill adults or Intermittent vancomycin dosing for young infants and children. vancomycin vancomycin vancomycin

When vancomycin is used for streptococcal endocarditis, the minimum duration of vancomycin therapy is 4 weeks. There is no evidence to support a 2-week course of vancomycin given synergistically with gentamicin.

¹ 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 adviceReturn

² 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

³ 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

⁴ Severe immediate hypersensitivity reactions include anaphylaxis, compromised airway, airway angioedema, hypotension and collapse.Return

⁵ 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