Staphylococcus aureus bacteremia: Difference between revisions

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Staphylococcus aureus bacteremia
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(added specific doses for IV and oral therapy)
 
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**Adjust based on serum trough before every fourth dose
  
**Adjust based on serum trough before every fourth dose
 
**Target trough 15-20
  
**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]], [[Infective endocarditis|endocarditis]]) with early oral antibiotics, including infections caused by [[Staphylococcus aureus]]
   
  +
=== Dosing ===
  +
  +
==== Penicillin- or Methicillin-Susceptible Strains ====
  +
{| class="wikitable"
  +
!Antibiotic
  +
!Renal Function
  +
!Standard Dose
  +
!Critical Illness Dose†
  +
|-
  +
| rowspan="4" |[[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
  +
|-
  +
| rowspan="3" |[[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
  +
|-
  +
| rowspan="4" |[[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 ======
  +
{| class="wikitable"
  +
!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 ======
  +
{| class="wikitable"
  +
!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 ====
  +
{| class="wikitable"
  +
!Silo
  +
!IV Antibiotic
  +
!Suggested First-Line
  +
! Suggested Second-Line (ordered)
  +
|-
  +
| rowspan="2" | PSSA
  +
|[[benzylpenicillin]]
  +
|[[amoxicillin]]
  +
|[[flucloxacillin]]/[[dicloxacillin]], [[cefalexin]]/[[cefadroxil]], [[linezolid]]
  +
|-
  +
|([[Flucloxacillin|flu]])[[cloxacillin]]
  +
|[[flucloxacillin]]/[[dicloxacillin]]
  +
|[[amoxicillin]], [[cefalexin]]/[[cefadroxil]], [[linezolid]]
  +
|-
  +
| rowspan="2" |MSSA
  +
|([[Flucloxacillin|flu]])[[cloxacillin]]
  +
|[[flucloxacillin]]/[[dicloxacillin]]
  +
|[[cefalexin]]/[[cefadroxil]], [[linezolid]]
  +
|-
  +
|[[cefazolin]]
  +
|[[cefalexin]]/[[cefadroxil]]
  +
|[[flucloxacillin]]/[[dicloxacillin]], [[linezolid]]
  +
|-
  +
| rowspan="2" |MRSA
  +
|[[vancomycin]]/[[daptomycin]]
  +
|[[linezolid]]
  +
|[[fluoroquinolone]]+[[rifampin]], [[TMP-SMX]], [[fusidic acid]]+[[rifampin]]
  +
|-
  +
|[[vancomycin]]/[[daptomycin]]+[[cefazolin]]
  +
|[[linezolid]]
  +
|[[fluoroquinolone]]+[[rifampin]], [[TMP-SMX]], [[fusidic acid]]+[[rifampin]]
  +
|}
  +
{| class="wikitable"
  +
!Antibiotic
  +
!Renal Function
  +
!Suggested Dose
  +
!Notes
  +
|-
  +
| rowspan="5" |[[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
  +
|
  +
|-
  +
| rowspan="6" |[[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
  +
|
  +
|-
  +
| rowspan="4" |[[cefalexin]]
  +
|normal
  +
|1 g q6h ± [[probenecid]]
  +
|
  +
|-
  +
|CrCl <10
  +
|1 g q12h
  +
|
  +
|-
  +
|CRRT
  +
|1 g q6h
  +
|
  +
|-
  +
|HD/PD
  +
|1 g q12h
  +
|
  +
|-
  +
| rowspan="4" |[[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
  +
|
  +
|-
  +
| rowspan="4" |[[dicloxacillin]]
  +
|normal
  +
|1 g q6h
  +
|
  +
|-
  +
|CrCl <10
  +
|1 g q8h
  +
|
  +
|-
  +
|CRRT
  +
|1 g q6h
  +
|
  +
|-
  +
|HD/PD
  +
|1 g q8h
  +
|
  +
|-
  +
|[[doxycycline]]
  +
|any
  +
|100 mg q12h
  +
|
  +
|-
  +
| rowspan="4" |[[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
  +
|
  +
|-
  +
| rowspan="5" |[[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
  +
|
  +
|-
  +
| rowspan="4" |[[linezolid]]
  +
|normal
  +
|600 mg q12h
  +
|
  +
|-
  +
|CrCl <10
  +
|600 mg q24h
  +
|
  +
|-
  +
|CRRT
  +
|600 mg q12h
  +
|
  +
|-
  +
|HD/PD
  +
|600 mg q24h
  +
|
  +
|-
  +
|[[moxifloxacin]]
  +
|any
  +
|400 mg daily
  +
|
  +
|-
  +
| rowspan="3" |[[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
  +
|
  +
|-
  +
| rowspan="2" |[[rifampin]]
  +
|any (weight <60kg)
  +
|600 mg daily
  +
|
  +
|-
  +
|any (weight >60 kg)
  +
|900 mg daily
  +
|
  +
|-
  +
|[[tedizolid]]
  +
|any
  +
|200 mg q24h
  +
|
  +
|-
  +
| rowspan="4" |[[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
 
==Further Reading==
  
==Further Reading==
   

Latest revision as of 12:45, 4 April 2024

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:
    • 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

Further Reading

References

  1. ^  Anthony D. Bai, Carson KL. Lo, Adam S. Komorowski, Mallika Suresh, Kevin Guo, Akhil Garg, Pranav Tandon, Julien Senecal, Olivier Del Corpo, Isabella Stefanova, Clare Fogarty, Guillaume Butler-Laporte, Emily G. McDonald, Matthew P. Cheng, Andrew M. Morris, Mark Loeb, Todd C. Lee. Staphylococcus aureus bacteremia mortality: A systematic review and meta-analysis. Clinical Microbiology and Infection. 2022. doi:10.1016/j.cmi.2022.03.015.
  2. ^  Sarah Tubiana, Xavier Duval, François Alla, Christine Selton-Suty, Pierre Tattevin, François Delahaye, Lionel Piroth, Catherine Chirouze, Jean-Philippe Lavigne, Marie-Line Erpelding, Bruno Hoen, François Vandenesch, Bernard Iung, Vincent Le Moing. The VIRSTA score, a prediction score to estimate risk of infective endocarditis and determine priority for echocardiography in patients with Staphylococcus aureus bacteremia. Journal of Infection. 2016;72(5):544-553. doi:10.1016/j.jinf.2016.02.003.
  3. ^  Thomas W van der Vaart, Jan M Prins, Robin Soetekouw, Gitte van Twillert, Jan Veenstra, Bjorn L Herpers, Wouter Rozemeijer, Rogier R Jansen, Marc J M Bonten, Jan T M van der Meer. Prediction Rules for Ruling Out Endocarditis in Patients With Staphylococcus aureus Bacteremia. Clinical Infectious Diseases. 2021;74(8):1442-1449. doi:10.1093/cid/ciab632.

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