Empirical therapy for Staphylococcus aureus bacteraemia

If gram-positive cocci in clusters are identified by Gram stain of blood samples, assume the patient has Staphylococcus aureus bacteraemia, even if they appear well. While awaiting the results of susceptibility testing, use combination therapy.

For empirical therapy for S. aureus bacteraemia in adults and children 1 month or older, as a 2-drug regimen, useLegg, 2023:

vancomycin intravenously; see advice on duration of therapy vancomycin vancomycin vancomycin

adult: 25 mg/kg (actual body weight) rounded up to nearest 125 mg, up to 3 g, as a loading dose. See Calculated vancomycin loading dosage in critically ill adults for calculated weight-based loading doses. Subsequent doses are dependent on weight and kidney function; see Intermittent vancomycin dosing for critically ill adults

child: for initial dosing, see Intermittent vancomycin dosing for young infants and children

PLUS EITHER

1cefazolin 2 g (child: 50 mg/kg up to 2 g) intravenously, 8-hourly. For patients with septic shock or requiring intensive care support, use a 6-hourly dosing interval1. For dosage adjustment in adults with kidney impairment, see cefazolin dosage adjustment. See advice on duration of therapy cefazolin cefazolin cefazolin

OR

1flucloxacillin 2 g (child: 50 mg/kg up to 2 g) intravenously, 6-hourly. For patients with endocarditis or septic shock, or those requiring intensive care support, use a 4-hourly dosing interval2. For dosage adjustment in adults with kidney impairment, see flucloxacillin intravenous dosage adjustment. See advice on duration of therapy. flucloxacillin flucloxacillin flucloxacillin

For empirical therapy for S. aureus bacteraemia in neonates, as a 2-drug regimen, useMcMullan, 2020:

vancomycin intravenously; for initial dosing, see Intermittent vancomycin dosing for young infants. See advice on duration of therapy vancomycin

PLUS EITHER

1cefazolin intravenously; see advice on duration of therapy cefazolin

postnatal age less than 8 days and weighing less than 2 kg: 25 mg/kg 12-hourly

postnatal age less than 8 days and weighing 2 kg or more: 50 mg/kg 12-hourly

postnatal age 8 days or older and weighing less than 2 kg: 25 mg/kg 8-hourly

postnatal age 8 days or older and weighing 2 kg or more: 50 mg/kg 8-hourly

OR

1flucloxacillin 25 mg/kg intravenously, 4-hourly; see advice on duration of therapy. flucloxacillin

Accumulating evidence suggests that cefazolin is as effective as flucloxacillin for the treatment of methicillin-susceptible S. aureus bacteraemia and may have lower risk of acute kidney injury. However, there are no published randomised controlled trials comparing cefazolin with flucloxacillin for this indication.

For patients who have had a nonsevere (immediate or delayed) or a severe immediate3 hypersensitivity reaction to a penicillin, use vancomycin plus cefazolin (see dosage above).

For patients who have had a severe delayed4 hypersensitivity reaction to a penicillin, use vancomycin as monotherapy (see dosage above).

Modify therapy based on the results of culture and susceptibility testing – see Directed therapy for Staphylococcus aureus bacteraemia.

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 for patients with septic shock or requiring 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.Return
2 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 for patients with endocarditis or septic shock, or those requiring intensive care support, a modified dosage of flucloxacillin 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 flucloxacillin (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.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