The Pros and CoNS of Staphylococcal Bacteraemia

Staphylococcus aureus in blood cultures makes patients really unwell and is a common cause of sepsis, the treatment of which should ideally be started within 1 hour otherwise mortality rises 7% per hour delayed. So it’s important to know and recognise this bacterium and more importantly to be able to decipher the “gobbledygook” terminology the Microbiologist uses when they relay the result!

A patient, in his mid-50s, presents with tachycardia, hypotension, confusion and poor urine output. There is no obvious source of infection: the chest X-ray is normal, the urine is negative on dipstick and there is no cellulitis. Keep your cool but recognise this pattern (tachycardia, hypotension, confusion and poor urine output), this is sepsis and it kills rapidly. Initial management is to call for senior support; administer oxygen, fluids and then start antibiotics. Ideally take your blood cultures before giving antibiotics however DO NOT delay giving these. Empirical treatment of sepsis is generally IV Piptazobactam but know your own local hospital policy.

The next day the blood cultures are positive and a Gram-positive coccus in clumps is seen in the Gram film (this is the most common appearance of a positive blood culture) but what does this “gobbledygook” terminology mean?

Gram-positive cocci that form clumps in blood cultures are always Staphylococci (except for a few oddities only Microbiologists really need worry about!). Staphylococci are most frequent because 1) they are a common cause of infection 2) they are the most common skin contaminants. So how do you tell a contaminant from an infection? As a general rule Coagulase-negative Staphylococci are likely to be contaminants whereas Staphylococcus aureus is almost always significant. Still none the wiser about how to tell them apart? Read on...

What do Microbiologists mean when they say a Staphylococcus is Coagulase-negative? Well, essentially what this means is that the Staphylococcus is not Staphylococcus aureus; as Staphylococcus aureus is “Coagulase-positive”. The term “Coagulase-negative Staphylococcus” often shortened to CoNS, would perhaps be more helpfully described as “Staphylococcus sp. which is not Staphylococcus aureus” rather than Coagulase-negative Staphylococcus. So where did this “gobbledygook” terminology come from?!

In modern microbiology laboratories we tend to rely on machines, such as MaldiTOF, to tell us what a microorganism is however traditionally laboratories distinguished Staphylococcus aureus from other Staphylococcus spp. by being the only Staphylococcus to give positive results in ALL three tests:

• Coagulase (an enzyme that coagulates serum) result: Staphylococcus aureus is Coagulase positive (i.e. not a Coagulase-negative Staphylococcus)
  
• DNAse (an enzyme that breaks down DNA) result: Staphylococcus aureus is DNAse  positive
  
• Clumping factor (commonly known as slide coagulase...but this is an entirely different test to Coagulase) result: Staphylococcus aureus produces clumping factor
  

We still revert to using these tests when the machines aren’t working for some reason. 

Click for larger image

These tests shaped how the term Coagulase-negative Staphylococcus was coined and it is still used today e.g. the Microbiologist calls and says “the blood culture contains a Coagulase-negative Staph, which is not significant” ...what the doctor probably hears is “blah blah blah, not significant”. The term is out dated but what do we use instead? In reality when a Microbiologist tells you, “It’s a Coagulase-negative Staphylococcus” what they are actually trying to tell you is that it is not Staphylococcus aureus!

• CoNS rarely cause disease and when grown from blood cultures more usually represent contamination from the skin
• Staphylococcus aureus is rarely a contaminant and causes serious infections e.g. sepsis

 
So are CoNS insignificant then?
There are lots of CoNS, some are more commonly isolated in microbiological specimens than others, the list below is not exhaustive. CoNS occasionally cause infection especially on intravascular devices but CoNS rarely make a patient septic.

Most frequently associated with human disease:

• S. epidermidis (the most common CoNS and usually a contaminant)
  
• S. lugdenensis (occasional cause of infective endocarditis)
  
• S. haemolyticus (no specific site of infection)
  
• S. saprophyticus (can cause urinary tract infections, commonly seen in pregnancy)

Rarely associated with human disease:

• S. hominis
  
• S. capitis
  
• S. pasteuri
  
• S. saccharolyticus
  
• S. simulans
  
• S. warneri
  
• S. schleiferi

Due to advances in technology, modern laboratories may now name these bacteria, but there is no specific clinical relevance associated with the individual microorganism. However, does reporting them by name encourage antibiotic prescribing?

CoNS contamination can occur with a breakdown in aseptic technique either because of poor technique or with difficult patients who are agitated or confused and who are moving around whilst you are trying to get the blood sample. Another reason for contamination is if there is a contraindication to the use of chlorhexidine to sterilise the skin such as in neonates and those with skin conditions such as eczema.

If a patient has a Staphylococcus aureus bacteraemia then the most likely sources of infection are:

• Skin (duration of treatment: 2 weeks)
• Bone (duration of treatment: 6 weeks)
• Joint (duration of treatment: 6 weeks)
• Heart (duration of treatment: 4-6 weeks)
• Intravascular devices e.g. cannula, central venous catheter (duration of treatment: 2 weeks)

Flucloxacillin is the most active agent against Staphylococcus aureus. IV is always used in Staphylococcus aureus bacteraemia. If the patient is allergic to Beta-lactams then IV Teicoplanin or IV Vancomycin can be used. The duration of treatment is dependent upon the probable source of infection (see above). It is really important to treat Staphylococcus aureus bacteraemias seriously as the mortality is 20% even with appropriate treatment. Patients do best if a source can be found and managed correctly and they receive at least 2 weeks of antibiotics.