Penicillin hypersensitivity regimens for empirical therapy of native valve infective endocarditis
Take 3 sets of blood for culture before starting antimicrobial therapy.
For empirical treatment of native valve endocarditis in adults and children who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, as a 3-drug regimen, use:
cefazolin 2 g (child: 50 mg/kg up to 2 g) intravenously, 8-hourly. 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
PLUS
vancomycin intravenously; for initial dosing, see Vancomycin dosing in adults or Intermittent vancomycin dosing for young infants and children. Loading doses are recommended for critically ill adults vancomycin vancomycin vancomycin
PLUS
gentamicin intravenously; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing1 gentamicin gentamicin gentamicin
adult: see Gentamicin initial dose calculator for adults for initial dose
child younger than 18 years: 7 mg/kg up to 560 mg for initial dose23
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 infective 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.
For patients who have had a severe immediate4 hypersensitivity reaction to a penicillin, the above cefazolin-containing regimen 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.
For patients who have had a severe immediate4 hypersensitivity reaction to a penicillin in whom cefazolin is not used, or for patients who have had a severe delayed5 hypersensitivity reaction to a penicillin, use gentamicin plus vancomycin (dosages as above).
Modify therapy based on the results of culture and susceptibility testing. Once the pathogen has been identified, ideally establish the minimum inhibitory concentration (MIC) of the chosen antimicrobial.
Stop gentamicin when susceptibilities are known, except for streptococcal endocarditis or enterococcal endocarditis, when it may be necessary to continue gentamicin for several weeks using multiple-daily dosing for synergistic therapy – see also Gentamicin in the management of infective endocarditis.