With respect to gram positive infections in the ICU:


a) What type of infections are commonly caused by Coagulase-negative Staphylococci (CoNS)?(10% marks)

b) What are the differences in clinical presentation between infections with CoNS and those with staphylococcus aureus? (40% marks)

c) What blood culture findings would suggest true bacteraemia rather than contamination with CoNS?(40% marks)

d) What empirical antimicrobial therapy is preferred for suspected CoNS infections? (10% marks) 

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College answer

a)    What infections are commonly caused by Coagulase-negative Staphylococcal Infections? 
•    Coagulase-negative Staphylococci (CoNS) commonly cause prosthetic device infections, such as:
o Prosthetic heart valves,
 o Prosthetic joints
o Vascular grafts
o Intra-vascular devices
o CNS shunts  
 
b)    Compared to Staphylococcus Aureus infections, what different clinical presentation is expected from infection with coagulase-negative staphylococci?                     
•    CoNS are less virulent than staphylococcus aureus, and hence: 
o    Signs of localised infection are subtle
o Rate of disease progression is slow
o Systemic findings are limited. 
o    Fever may be absent
o Acute phase reactants, may be normal or slightly elevated. 
o    Abscess formation commoner with S. Aureus
o Patients with S Aureus usually sicker 
 
c)    What blood culture findings (in addition to clinical suspicion) would suggest true bacteraemia rather than contamination with CoNS?                           
•    Multiple isolations of the same strain from separate cultures 
•    Growth of the strain within 48 hours 
•    Bacterial growth in both aerobic and anaerobic bottles. 
 
d)    Empirical antimicrobial therapy                                    
•    CoNS are usually resistant to Methicillin; hence, Vancomycin is the preferred empirical therapy. 
 

Discussion

Most of this discussion section (and the associated CoNS revision chapter) were generated using the comprehensive review by Davidson and Low at antimicrobe.org. 

a)

Specific infections caused by these organisms:

  • Urinary tract infections
  • Central or peripheral venous catheter related infections,
  • VP shunt infections
  • Pneumonia, 
  • Endophthalmitis
  • Surgical wound infections
  • Mastitis or breast abscess
  • Osteomyelitis
  • Native and prosthetic valve endocarditis
  • Prosthetic joint infections
  • Infections of pacemaker leads

b)

Classically, because these organisms are low virulence skin organisms, infections due to them are

  • indolent
  • superficial
  • related to breakdown of the skin barrier properties
  • limited to areas which are sequestered from the immune system
  • more common among immunocompromised hosts
  • less likely to stimulate a vigorous immune response

In contrast, S.aureus infection tends to progress more rapidly, cause more severe infections, affect relatively healthy people, stimulate a vigorous SIRS response, and occasionally produce a toxic-shock-like superantigen-driven syndrome.

c)

Blood culture findings suggestive of a true CoNS bacteraemia:

  • Number of positive cultures
  • Simultaneous cultures: Of a set of two cultures taken at the same time but from different sites, both grow the same CoNS. 
  • Rapid time to culture growth (i.e. large inoculum): Kassis et al (2009) found that a time to positive culture of less than 16 hours was suggestive of a large organisms count as measured by "colony-forming units".
  • Quantitative blood culture: a colony count <10 CFUs suggests contamination; Kassis et al (2009) found that of these patients had a good outcome even if they didn't get any antibiotics and their central line was left in situ.

The college answer refers to "bacterial growth in both aerobic and anaerobic bottles" as one of the parameters suggestive of "true" bacteraemia. Looking for evidence in support of this one lands on the influential and highly-referenced article by Kirchoff et al (1985), which documents 26 months of blood cultures from the University of Michigan Medical Center. The authors reported that "coagulase-negative staphylococci grew in both aerobic and anaerobic bottles in 85% of blood culture sets drawn during episodes of bacteremia, but in only 30% of the cultures thought to be contaminated".  Kirchoff et al also seem to be the reference for the "positive within 48 hours" comment. 

d)

The Sanford Guide recommends vancomycin as empiric therapy. Most CoNs (80-90%) are resistant to "classical" β-lactams, but sensitive to antistaphylococcal ones like flucloxacillin. Cephazolin and linezolid are alternatives. If a prosthetic device is infected but needs to remain in situ, rifampicin may be used over a long course.

References

John Jr, Joseph F., R. J. Davidson, and Donald E. Low. "Staphylococcus epidermidis and other Coagulase-Negative Staphylococci.Antimicrobial Therapy 1.

Foster, Timothy. "Staphylococcus." (1996).

Kassis, Christelle, et al. "Differentiating culture samples representing coagulase-negative staphylococcal bacteremia from those representing contamination by use of time-to-positivity and quantitative blood culture methods.Journal of clinical microbiology 47.10 (2009): 3255-3260.

Weinstein, M. P. "Contaminated or not? Guidelines for interpretation of positive blood cultures. WebM&M. January 2008. Agency for Healthcar Research and Quality, Rockville, MD." (2008).

Al-Mazroea, Abdulhadi Hassan. "Incidence and clinical significance of coagulase negative Staphylococci in blood." Journal of Taibah University Medical Sciences 4.2 (2009): 137-147.

Kirchhoff, Louis V., and John N. Sheagren. "Epidemiology and clinical significance of blood cultures positive for coagulase-negative staphylococcus." Infection Control & Hospital Epidemiology 6.12 (1985): 479-486.