Staphylococcal Bacteremias

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					Staphylococcal Bacteremias

 What is the appropriate choice and
        duration of therapy?

        Rashmi Tadiparthi
• Disease caused by staphylococcus was first described in 1880 by
• More than a 100 years later continues to be a dangerous pathogen
  with increasing prevalence and virulence.
• Humans are a natural reservoir with more than 50% healthy adults
  transiently colonized and 10-20% adults persistantly colonized.
• Colonization increases risk for subsequent infection.
• Type 1 DM, AIDS, Hemodialysis, IVDA and any
  qualititive/quantitative leukocyte function abnormality increases
  risk for colonization.
• Mortality from staphylococcal bacteremia ranges from 11-43%
• Change in APACHE score from day before to day of bacteremia
  influences outcome.
Staphylococci with Polymorphonuclear Leukocytes in a Sputum Sample (Gram's Stain,

                        Lowy, F. D. N Engl J Med 1998;339:520-532
     Types of Bacteremias

• Simple
• Uncomplicated
• Complicated
Criteria that determine duration of therapy include:
1) Clinical:
•   Removable focus of infection
•   Prosthetic material
•   Deep focus of infection
•   Response to therapy
2) Microbiologic
• Positive cultures 48-72hrs after initiation of therapy
3) Echocardiographic
• Evidence of valve vegetations by TEE
                  Clinical Criteria
•   Removable focus of infection: Low cure rate if catheter is
    left in place (17-18%). Increased rate of relapse with
    continued presence of intravascular foreign body.
•   Response to initial therapy: Persistence of fever and
    bacteremia for more than 3 days after starting therapy is
    statistically associated with increased risk for complications
    such as endocarditis and osteomyelitis. Also higher risk of
•   Prosthetic material such as cardiac valves and Deep focus of
    infection such vertebral osteomyelitis have higher rates of
    relapse with short courses.
• Routine use of 2D echocardiography has been
  suggested in patients with staphylococcus
  bacteremia due to high association often times
  with clinically inapparent infective endocarditis.
• Cost effectiveness of TEE( 96% sensitivity, 95%
  specificity) vs empiric therapy for IE was analysed
  and showed that TEE guided therapy was more
  cost effective that empiric therapy.
• Simple bacteremia:
  –   Removable focus of infection such as a vascular catheter
  –   No evidence of endocarditis by TEE
  –   No valvular abnormalities
  –   Negative cultures within 2-3 days of starting therapy

  Recommendation: 1 week of antimicrobial therapy
• Uncomplicated bacteremia:
  – Bacteremia in patients with cardiac valvular
    abnormalities but no evidence of IE by TEE.
  – Negative surveillance cultures but persistence of fever for
    3-4 days of start of therapy.

  Recommendation: 2 weeks of antimicrobial therapy
• Complicated bacteremia :
  – Associated with Infective endocarditis, deep focus of
  – Bacteremia 48-96 hrs after start of therapy.

  Recommendation: 4-6 weeks of antimicrobial therapy
         Antimicrobial Therapy for Serious S. aureus Infections

Lowy, F. D. N Engl J Med 1998;339:520-532
             Choice of therapy
• Nafcillin superior to vancomycin for MSSA
• Vancomycin is still drug of choice for MRSA bacteremia
• Combination therapy of beta lactam and aminoglycosides
  achieves rapid clearence of bacteria from blood stream
• Nafcillin + Gentamycin for MSSA vs Vancomycin
  +Gentamycin for MRSA.
• Rifampin is a potent antistaphylococcal drug used in
  combination with above regimen in prosthetic valve
• Used alone rifampin resistance emerges rapidly.
• Rifampin used also in combination with Fluoroquinolone
  to decrease emergence of resistance.
                      New Drugs
• Quinupristin/dafopristin:
   - Fixed 30/70 combination, streptogramin derivative
   - In the US this drug is FDA approved for treatment of
  complicated skin and soft tissue infections with VRE and
   - Synergistic action when combined with Beta lactams and
   - In a limited series of 90 patients with MRSA skin infections
  who had either failed or were intolerant to Vancomycin
  response to this drug was 71%.
  - Severe thrombophlebitis, must be given throgh a central line.
  - Arthralgia, myalgia and hyperbilirubinemia
                 New Drugs
• Daptomycin
   -In a series of 1100 patients with skin infections
  from MRSA Daptomycin had simillar cure rate as
  Vancomycin (75% vs 69%)
   -Currently FDA approved for skin and soft tissue
  infections with staph.aureus including MRSA.
   - Not used for pneumonias as it does not achieve
  high enough concentrations in the respiratory
                 New Drugs
• Lysostaphin: Used in combination with Vancomycin
  to sterilize valvular vegetations in rabbits.
• Linezolid: Oxazolidinone, bacteriostatic against
   - FDA approved for nosocomial pneumonia and skin
  infections from MRSA
   - Excellent tissue distribution.
    -Superior to Vancomycin in MRSA pneumonia ( 339
  patients with staph.aureus pneumonia, clinical cure
  rate was 59% vs 36% with vancomycin.)
•   Treatment of Staphylococcus bacteremia
    in adults.,
       Vance G Fowler Jr, Daniel J Sexton
•   Staphylococcus aureus infections.,
       Lowy F.D.

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