Coagulase-negative Staphylococci

Question 14 from the second paper of 2017 was the first question to directly ask about this group of bugs. Prior to that the CoNS group had played a fairly peripheral role in the exams, eg. in Question 23.1 from the first paper of 2013 where the candidates were asked 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 comprehensive review which goes beyond the requirements of a time-poor exam candidate,  one can go to the online article by Davidson and Low at antimicrobe.org. 

Microbiology of coagulase-negative Staphylococci

These cocci are Gram-positive catalase-positive and coagulase-negative. Broadly, you group staphylococci into those which produce coagulase (S.aureus) and those which do not (all others). Coagulase produced by S.aureus enables the conversion of fibrinogen to fibrin, i.e. it facilities blood coagulation. That covers staphylococci in a film of clotted blood, which in turn protects them from phagocytosis and immune detection. This distinction is therefore supposed to be clinically relevant, and the coagulase-negative staphylococci are therefore a low-virulence group because they remain "naked", unable to cloak themselves in this way. However, there is no direct evidence that coagulase is a virulence factor (Foster, 1996) and a few isolates of S.aureus have no coagulase, so this classification system is probably more folklore and tradition rather than science.

This group contains the following relevant members:

• S.epidermitis (IE)
• S. schleiferi (IE)
• S. lugdunensis (IE)
• S. haemolyticus (IE)
• S. saprophyticus (UTIs)
• S. warneri
• S. hominis
• S. capitis

Infections typically caused by coagulase-negative Staphylococci

In Question 14 from the second paper of 2017, the candidates were asked to contrast the clinical presentation of CoNS and S.aureus infectious processes. 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.

Host factors which favour infection include

• Immune compromise
• Foreign bodies (eg. CVC)
• Disrupted barrier function (wounds, burns etc)

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

Distinguishing contamination with CoNS from "true" bacteraemia

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. 
• 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.
• Growth in both aerobic and anaerobic bottles: The college answer to Question 14 from the second paper of 2017 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".   
• 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".  The college answer to Question 14 from the second paper of 2017 also references Kirchoff et al (1985), who found that growth within 48 hours was associated with a clinically significant bacteraemia in 83% of cases (and only in 63% of cases when the culture took longer). 

Additionally, there would have to be some sort of judgment call where the interpreter takes the result and considers the risk factors of the patient, i.e. is this patient likely to have a prosthetic device infection? Would such an infection be disastrous? 

Empirical antibiotics for CoNS bacteraemia

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, rifapicin may be used over a long course.