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)
Line 75: Line 75:
**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==


Revision as of 16:45, 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. ^  Bharath Raj Palraj, Larry M. Baddour, Erik P. Hess, James M. Steckelberg, Walter R. Wilson, Brian D. Lahr, M. Rizwan Sohail. Predicting Risk of Endocarditis Using a Clinical Tool (PREDICT): Scoring System to Guide Use of Echocardiography in the Management of Staphylococcus aureus Bacteremia. Clinical Infectious Diseases. 2015;61(1):18-28. doi:10.1093/cid/civ235.
  3. ^  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.

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