What is the appropriate choice and
duration of therapy?
• 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
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
Criteria that determine duration of therapy include:
• Removable focus of infection
• Prosthetic material
• Deep focus of infection
• Response to therapy
• Positive cultures 48-72hrs after initiation of therapy
• Evidence of valve vegetations by TEE
• 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.
- 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
-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
• 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
Vance G Fowler Jr, Daniel J Sexton
• Staphylococcus aureus infections.,