summary

S. aureus bacteraemia Never a contaminant — one positive bottle is SAB. ID consultation (mortality benefit), repeat blood cultures at 48 h until negative, TTE in every adult, source control. MSSA: cefazolin or cloxacillin (SNAP (2026): cefazolin non-inferior, less nephrotoxicity). MRSA: vancomycin. Duration counts from the first negative culture: 14 days if no deep-seated focus; 4–6 weeks if endocarditis or metastatic infection. IDSA/ESCMID 2026 replaces “uncomplicated/complicated” with low-risk vs increased-risk.

plan

S. aureus bacteraemia bundle

ID consult
repeat blood cultures × 2 at 48 h, then q24–48h until negative — day of first negative culture = day 1 of therapy
empiric vancomycin 25–30 mg/kg IV load, then AUC-guided (400–600 mg·h/L) until susceptibilities
MSSA → cefazolin 2 g IV q8h or cloxacillin 2 g IV q4h (stop vancomycin)
TTE in all; TEE if intracardiac device, predisposing valve disease, cultures positive ≥48 h, embolic events, or multiple foci
remove CVC promptly; drain collections; examine spine, joints, prosthetic material, and skin
if increased-risk and no focus found: whole-body imaging (FDG-PET/CT, or targeted CT/ultrasound)
duration: 14 days minimum from first negative culture; 4–6 weeks if deep-seated focus or endocarditis

local antibiogram

MRSA proportion among S. aureus bacteraemia varies across Canadian centres — empiric vancomycin until susceptibilities, then switch fast for MSSA.

risk stratification (IDSA/ESCMID 2026)

Key risk factors for deep-seated/metastatic infection or relapse:

community-onset SAB
positive blood culture ≥48 h after the first
intracardiac device (prosthetic valve, pacemaker/ICD)

Other risk factors: predisposing valve disease, injection drug use, endovascular graft, SAB within previous 90 days, signs of deep-seated infection, embolic phenomena, multiple foci, unknown source.

category	features	typical management
low-risk	hospital-onset, removable focus (e.g. line) removed, cultures clear <48 h, no device, no deep focus on assessment	14 days; oral step-down possible
increased-risk, no deep focus found	any risk factor above, full work-up negative	14 days (longer if prolonged bacteraemia or incomplete work-up)
deep-seated/metastatic focus	endocarditis, vertebral osteomyelitis, septic arthritis, abscess, septic thrombophlebitis	4–6 weeks, source control

antibiotic choice

MSSA

cefazolin 2 g IV q8h or cloxacillin 2 g IV q4h
SNAP (2026): cefazolin non-inferior to flucloxacillin/cloxacillin for 90-day mortality (15.0% vs 17.0%) with fewer nephrotoxic effects
cefazolin is also simpler (q8h, OPAT-friendly) and usable in most penicillin-allergic patients — see penicillin allergy
switch off vancomycin as soon as MSSA is confirmed — vancomycin is inferior for MSSA
CNS infection: cloxacillin preferred (cefazolin CNS penetration uncertain)

MRSA

vancomycin, AUC-guided (400–600 mg·h/L) or continuous infusion per local protocol
daptomycin 8–10 mg/kg IV q24h if vancomycin MIC ≥2 mg/L, persistent bacteraemia, or AKI — Fowler (2006): non-inferior to standard therapy; not for pneumonia (inactivated by surfactant)
persistent bacteraemia ≥5–7 days despite source control → ID-directed salvage (daptomycin + β-lactam, or ceftaroline)

combination therapy — not routine

CAMERA2 (2020): adding an anti-staphylococcal β-lactam to vancomycin/daptomycin for MRSA → no mortality benefit, more AKI
ARREST (2018): adjunctive rifampicin → no benefit overall
gentamicin for native-valve SAB: no benefit, nephrotoxic — avoid
rifampicin still used in prosthetic valve/device or retained hardware infection (with ID)

oral step-down

SABATO (2024): in low-risk SAB, switching to oral after 5–7 days IV (mostly TMP-SMX) to complete 14 days was non-inferior to continued IV for 90-day SAB complications.

Eligibility was strict (~4% of screened patients):

removable focus removed, or no focus with clear rapid response
no endocarditis, prosthetic material, deep-seated focus, or persistent bacteraemia
afebrile, cultures cleared, able to absorb oral therapy

Endocarditis step-down is a separate question — see infective endocarditis (POET).

source control

remove CVCs, PICCs, and haemodialysis catheters — do not attempt salvage in SAB
drain abscesses; washout of septic joints
cardiac device (pacemaker/ICD) with SAB → high rate of device infection; ID + EP input on complete extraction even if TEE shows no lead vegetation
persistent positive cultures at 48–72 h → look again for an undrained focus

duration

scenario	duration (from first negative culture)
low-risk, no deep focus	14 days (oral step-down possible after 5–7 days IV if SABATO-eligible)
increased-risk, full work-up negative	14 days; longer if bacteraemia prolonged or work-up incomplete
native-valve endocarditis	6 weeks
prosthetic-valve endocarditis	≥6 weeks + rifampicin, + gentamicin first 2 weeks
vertebral osteomyelitis, epidural abscess	6–8 weeks
septic arthritis / other metastatic foci	4–6 weeks

traps

one positive bottle with S. aureus = SAB — never dismiss as contamination
duration counts from the first negative culture, not the first dose
“uncomplicated” is no longer a label to assign before full work-up — TTE, repeat cultures, and examination come first
negative TTE does not exclude endocarditis in patients with risk features → TEE
back pain + SAB → MRI spine (vertebral osteomyelitis/epidural abscess)
continuing vancomycin for MSSA “because it’s working” — switch to cefazolin/cloxacillin
new AKI on vancomycin → switch rather than reduce dose into a sub-therapeutic range

staphylococcus aureus bacteraemia