Staphylococcus aureus bacteremia

Background

Classification

• Community-onset: positive blood culture obtained within 48 hours of presentation
• Nosocomial: positive blood culture obtained after 48 hours of presentation

Etiology

• IVDU
• Poor dentition
• Dental work

Clinical Manifestations

• Often non-specific fevers and chills, diagnosed on blood cultures
• May have back pain unrelated to spinal osteomyelitis
• May present with focus of metastatic disease

Prognosis

• Associated with about 30% mortality1
• Mortality halved by ID consult in observational studies
• Prognosis worse with
  • Increased age
  • Female sex
  • Pneumonia or source unknown
  • Dementia
  • Increasing comorbidities
  • Shock at time of presentation
  • Institutionalized patient

Investigations

• Repeat blood cultures every 24 to 48 hours until negative
• Transthoracic echo (TTE) or transesophageal echo (TEE)
  • A modern TTE that is good-quality and shows normal valves is quite good, though TEE is still better
  • TEE is strongly suggested in certain cases:
    • Cerebral or peripheral emboli
    • Meningitis
    • Implantable cardiac device or prosthetic heart valve
    • Prior infective endocarditis
    • Native valve disease
    • Injection drug use
    • Persistent bacteremia beyond 72 hours
  • Can also use VIRSTA score to decide if they need TEE2
    • Highest sensitivity (~99%), though specificity only 35%
    • The high sensitivity gives very high negative predictive value of ~99%
    • Likely preferred to others like the PREDICT score, which has lower sensitivity though higher specificity3

Management

• Infectious diseases consultation

Echocardiography

• Must rule out endocarditis! TTE, followed by TEE if suspicion remains high (see VIRSTA score)
  • Low risk for endocarditis (no TEE) if all of the following:
    • No intracardiac device
    • Sterile follow-up blood cultures within 4 days from the initial set
    • No hemodialysis
    • Nosocomial acquisition
    • Absence of secondary foci
    • No clinical signs of endocarditis
  • Uncomplicated if all of the following:
    • Endocarditis is excluded
    • No implanted prostheses
    • Blood cultures clear by 2-4 days
    • Defervesces within 72 hours
    • No evidence of metastases
    • +/- identified source has been removed

Antimicrobial Therapy

• Two-week course acceptable if uncomplicated, otherwise 4-6 weeks based on clinical course and underlying foci of infection
• MSSA: cloxacillin 2g IV q4h for 2 weeks (cefazolin as an alternative)
• MRSA: vancomycin 1g IV q12h for 2 weeks
  • Adjust based on serum trough before every fourth dose
  • Target trough 15-20
• Standard of care is still currently IV therapy for the duration, though there is emerging evidence for treating a number of deep-seated infections (osteomyelitis, endocarditis) with early oral antibiotics, including infections caused by Staphylococcus aureus

Dosing

Penicillin- or Methicillin-Susceptible Strains

Antibiotic	Renal Function	Standard Dose	Critical Illness Dose†
benzylpenicillin (pen G)	eGFR >50	1.8 g (3 MU) q4h	2.4 g (4 MU) q4h
	eGFR 10-50	1.8 g (3 MU) q6h	1.8 g (3 MU) q4h
	eGFR <10	1.8 g (3 MU) load, then 1.2 g (2 MU) q8h	2.4 g load, then 1.2 g (2 MU) q6h
	CRRT	1.2 g (2 MU) q6h	1.8 g (3 MU) q6h
flucloxacillin	eGFR ≥10	2 g q6h	2 g q4h
	eGFR <10	1 g q6h	1 g q4h
	CRRT	2 g q6h	2 g q6h
cloxacillin	any	2 g q4h	2 g q4h
cefazolin	eGFR >40	2 g q8h	2 g q6h
	eGFR 20-40	2 g q12h	2 g q12h
	eGFR <20	1 g q24h	1 g q24h
	CRRT	2 g q12h	2 g q12h

*† Critical illness dosing should be used for patients with septic shock, admitted to ICU, with endocarditis, or with CNS infection (excluding spinal epidural abscess)

• • May be decreased to standard dosing once no longer requiring mechanical ventilation or vasopressors for at least 24 hours

Methicillin-Resistant Strains

Vancomycin Dosing

• Vancomycin dosing may follow local guidelines
• Includes loading dose of 25 mg/kg (max 3 g) if considered appropriate by the physician, then maintenance dosing at 15-20 mg/kg q12h, adjusted to target AUC 400-600 mg h/L or trough 10-20 mg/L

Daptomycin Dosing

Renal Function	Suggested Dose
eGFR >50	8-10 mg/kg q24h
eGFR 11-50	6-8 mg/kg q24h
eGFR ≤10	8 mg/kg q48h
CRRT	8 mg/kg q48h
HD	8 mg/kg q48h, given after dialysis

Adjunctive Cefazolin Dosing

Renal Function	Suggested Dose
CrCl >40	2 g q8h
CrCl 20-40	2 g q12h
CrCl <20	1 g q24h
CRRT	1 g q8h or 2 g q12h
HD	2 g after each dialysis session

Early Oral Switch

Silo	IV Antibiotic	Suggested First-Line	Suggested Second-Line (ordered)
PSSA	benzylpenicillin	amoxicillin	flucloxacillin/dicloxacillin, cefalexin/cefadroxil, linezolid
	(flu)cloxacillin	flucloxacillin/dicloxacillin	amoxicillin, cefalexin/cefadroxil, linezolid
MSSA	(flu)cloxacillin	flucloxacillin/dicloxacillin	cefalexin/cefadroxil, linezolid
	cefazolin	cefalexin/cefadroxil	flucloxacillin/dicloxacillin, linezolid
MRSA	vancomycin/daptomycin	linezolid	fluoroquinolone+rifampin, TMP-SMX, fusidic acid+rifampin
	vancomycin/daptomycin+cefazolin	linezolid	fluoroquinolone+rifampin, TMP-SMX, fusidic acid+rifampin

Antibiotic	Renal Function	Suggested Dose	Notes
amoxicillin	normal	1 g q6h ± probenecid
	CrCl 10-30	1 g q8h
	CrCl <10	1 g q12h
	CRRT	1 g q8h
	HD/PD	1 g q12h
cefadroxil	normal	1 g q12h
	CrCl 10-50	1 g then 500 mg q12h
	CrCl <10	1 g then 500 mg q36h
	CRRT	1 g then 500 mg q12h
	HD	1 g then 1 g post-HD
	PD	500 mg q24h
cefalexin	normal	1 g q6h ± probenecid
	CrCl <10	1 g q12h
	CRRT	1 g q6h
	HD/PD	1 g q12h
ciprofloxacin	normal	750 mg q12h
	CrCl <30	750 mg q24h
	CRRT	250-500 mg q12h
	HD/PD	750 mg q24h
clindamycin	any	450 mg q8h
cloxacillin	any	1 g q6h
dicloxacillin	normal	1 g q6h
	CrCl <10	1 g q8h
	CRRT	1 g q6h
	HD/PD	1 g q8h
doxycycline	any	100 mg q12h
flucloxacillin	normal	1 g q6h
	CrCl <10	1 g q8h
	CRRT	1 g q6h
	HD/PD	1 g q8h
fusidic acid	any	500 mg q24h
levofloxacin	normal	750 mg q24h
	CrCl 20-49	750 mg q48h
	CrCl <20	750 mg then 500 mg q48h
	CRRT	250 mg q24h
	HD/PD	750 mg then 500 mg q48h
linezolid	normal	600 mg q12h
	CrCl <10	600 mg q24h
	CRRT	600 mg q12h
	HD/PD	600 mg q24h
moxifloxacin	any	400 mg daily
probenecid	CrCl ≥60	500 mg with each dose of β-lactam
	CrCl 30-60	250 mg with each dose of β-lactam
	CrCl <30	avoid use
rifampin	any (weight <60kg)	600 mg daily
	any (weight >60 kg)	900 mg daily
tedizolid	any	200 mg q24h
TMP-SMX	normal	2 DS q12h or 1 DS q8h
	CrCl 26-50	normal dose for 14 days then 1 DS q12h
	CrCl 15-25	normal dose for 3 days then 2 DS q24h
	CrCl <15	avoid use

Adjunctive Clindamycin

• Clindamycin 600 mg IV q8h for 5 days as adjunctive therapy regardless of clindamycin susceptibility
• Alternative is 450 mg p.o. q8h for 5 days, though preference for IV