What is a clinically significant coagulase-negative staph bacteraemia? This has exam relevance. Question 14 from the second paper of 2017 asked various detailed questions about coagulase-negative staphylococci, and  Question 23.1 from the first paper of 2013 asks the candidate how they would react to a S.epidermidis growing from a culture which was drawn from a central line in the process of insertion. For a coherent answer, the time-poor exam candidate is redirected to the LITFL article on CRBSI and CLABSI. That is what you call a "brief summary". In contrast, what follows here may represent spontaneous prose.

Blood cultures taken from central lines

So, your CVC culture is positive. What could this mean?

Positive cultures collected from the CVC could mean one of three things:

  • CVC is colonised by organisms which are benign and doing no harm; in fact 15-25% of CVCs are colonised (usually by coagulase-negative staph) and the patients are fine, without any features of infection.
  • CVC is colonised by organisms which are causing a clinically significant bacteraemia.
  • CVC may still be colonised, but the culture grew organisms representing a systemic bacteraemia which did not originate in the CVC.

Generally speaking, the practice of taking cultures from CVCs is discouraged by guideline-makers (eg. the American College of Physicians).

Arguments against taking cultures from the central line

However:

  • There are no good quality studies to confirm that these concerns are valid; none of the available studies were blinded, and there is thus far no "gold standard" definition of bacteraemia against which they could be held.

Discriminating false positives from true positives

A recent (2006) review article suggests some strategies to help you tell which CVC culture warrants CVC removal, and which does not.

Identity of the organism

Organisms which Usually Represent "True" Bacteraemia:
  • Staphylococcus aureus
  • Streptococcus pneumoniae
  • Streptococcus pyogenes
  • Streptococcus agalactiae
  • Escherichia coli
  • Enterobacteriaceae
  • Pseudomonas aeruginosa
  • Listeria monocytogenes
  • Neisseria meningitidis
  • Neisseria gonorrhoeae
  • Haemophilus influenzae
  • Bacteroides fragilis
  • Cryptococcus neoformans
  • Candida albicans
  • Conversely, there is also a selection of organisms which almost always represent contamination:
Organisms which Usually Represent CVC Colonisation:
  • Corynebacterium sp.
  • Bacillus sp. other than Bacillus anthracis
  • Propionibacterium acnes
  • Micrococcus sp.
  • Viridans group streptococci
  • Enterococci
  • Clostridium perfringens
  • Coagulase-negative staphylococci.

Coagulase negative Staphylococci:

Coagulase-negative staphylococci represent an area of uncertain twilight between these two groups. For most, these are benign contaminants. For some, they are horrific valve-eating pathogens. Practically speaking, it does not matter to the intensivist whether the blood culture represents systemic bacteraemia or catheter colonisation; rather it is more important to determine whether the clinical scenario warrants concern. If you're concerned, you will remove the line and start antibiotics.

 Question 23.1 from the first paper of 2013 asks the candidate how they would react to a S.epidermidis growing from a culture which was drawn from a central line in the process of insertion.

Risk factors for clinically significant S.epidermidis bacteraemia:
  • Anyone at risk of native valve endocarditis
  • Artifical valves
  • History of rheumatic heart disease
  • Immunosuppressed
  • Implated pacemaker, or any other surgical implant
  • Low birth infant
  • Elderly person (>65 years of age)

In other words, people with the above risk factors are much more likely to have a serious problem if they really do have S.epidermidis in their blood; which means that the risk-benefit balance favours the removal of the CVC and the commencement of antibiotics.

Differential time to positivity

  • When you draw a positive blood culture from the CVC, you are left guessing: is the CVC really contaminated with that organism, or did I just suck up bacteraemic blood through a nice clean CVC (and the source is elsewhere)?
  • Differential time to positivity is a potential means of discriminating "true" CVC -related bacteraemia from systemic bacteraemia.
  • One takes two sets of cultures: one from the central line, and another peripherally.
  • Basically, if the CVC culture becomes positive earlier than the peripheral culture, the CVC is likely to be the source.
  • Differential time to positivity of 120 minutes or more was associated with 81% sensitivity and 92% specificity for short term catheters. It is less specific in long-term lines.
  • However, one ends up taking two sets of cultures, which is somewhat counterproductive if one's intention is to save money on laboratory fees.

Number of positive culture sets

  • For true bacteraemias, multiple blood culture sets will usually grow the same organism .
  • For patients with CVCs and a coagulase negative staph growing from different numbers of cultures, the positive predictive value was:
    • 55% when one of one culture was positive,
    • 20% when one of two cultures was positive,
    • only 5% when one of three cultures was positive.
  • The abovementioned multiple culture sets should be taken from different sites. For two positive culture sets, the positive predictive value was:
    • 98% if both samples were obtained through the vein
    • 96% if one sample was obtained through a central line
    • only 50% if both samples were obtained through a catheter.

References

De Leon, Samuel Ponce, and Richard P. Wenzel. "Hospital-acquired bloodstream infections with Staphylococcus epidermidis: review of 100 cases."The American journal of medicine 77.4 (1984): 639-644.

Haslett, T. M., et al. "Microbiology of indwelling central intravascular catheters."Journal of clinical microbiology 26.4 (1988): 696-701.

Stohl, Sheldon, et al. "Blood cultures at central line insertion in the intensive care unit: comparison with peripheral venipuncture." Journal of clinical microbiology 49.7 (2011): 2398-2403.

Beekmann, Susan E., Daniel J. Diekema, and Gary V. Doern. "Determining the clinical significance of coagulase-negative staphylococci isolated from blood cultures." Infection control and hospital epidemiology 26.6 (2005): 559-566.

Raad, Issam, et al. "Impact of central venous catheter removal on the recurrence of catheter-related coagulase-negative staphylococcal bacteremia."Infection control and hospital epidemiology (1992): 215-221.

Raad, Issam, et al. "Management of the catheter in documented catheter-related coagulase-negative staphylococcal bacteremia: remove or retain?."Clinical infectious diseases 49.8 (2009): 1187-94.

Raad, Issam, et al. "Differential time to positivity: a useful method for diagnosing catheter-related bloodstream infections." Annals of Internal Medicine 140.1 (2004): 18-25.

Chu, Vivian H., et al. "Emergence of coagulase-negative staphylococci as a cause of native valve endocarditis." Clinical infectious diseases 46.2 (2008): 232-242.

Blot, François, et al. "Earlier positivity of central-venous-versus peripheral-blood cultures is highly predictive of catheter-related sepsis." Journal of clinical microbiology 36.1 (1998): 105-109.

DesJardin, Jeffrey A., et al. "Clinical utility of blood cultures drawn from indwelling central venous catheters in hospitalized patients with cancer."Annals of internal medicine 131.9 (1999): 641-647.

Hall, Keri K., and Jason A. Lyman. "Updated review of blood culture contamination." Clinical microbiology reviews 19.4 (2006): 788-802.

Bates, David W., Lee Goldman, and Thomas H. Lee. "Contaminant blood cultures and resource utilization: the true consequences of false-positive results." JAMA 265.3 (1991): 365-369.

Souvenir, David, et al. "Blood cultures positive for coagulase-negative staphylococci: antisepsis, pseudobacteremia, and therapy of patients." Journal of clinical microbiology 36.7 (1998): 1923-1926.

Bates, David W., and Thomas H. Lee. "Rapid classification of positive blood cultures: prospective validation of a multivariate algorithm." Jama 267.14 (1992): 1962-1966.

Weinstein, Melvin P., et al. "The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults." Clinical Infectious Diseases 24.4 (1997): 584-602.

Gowardman, J. R., et al. "Central venous catheter-related bloodstream infections: an analysis of incidence and risk factors in a cohort of 400 patients." Intensive care medicine 24.10 (1998): 1034-1039.

Beekmann, Susan E., Daniel J. Diekema, and Gary V. Doern. "Determining the clinical significance of coagulase-negative staphylococci isolated from blood cultures." Infection Control 26.06 (2005): 559-566.

Tokars, Jerome I. "Predictive value of blood cultures positive for coagulase-negative staphylococci: implications for patient care and health care quality assurance." Clinical infectious diseases 39.3 (2004): 333-341.