Tag Archives: blood cultures

“When the bugs take their time…”

You are probably familiar with the scenario… A blood culture takes a couple of days to become positive. A Gram stain shows Gram negative rods. The plates are subbed but after another couple of days there is still no growth on the plates. The clinicians are getting impatient and are phoning the lab looking for an identification…

It is certainly a frustrating situation but one that occurs not infrequently.

Is there anything that can be done to help the clinician, and more importantly the patient, whilst we are waiting for the organism to grow?

There are several organisms to consider in this sort of scenario. We should be thinking about HACEK organisms, anaerobes, Pasteurella spp., oxidative non-fermentors like Burkholderia spp., Capnocytophaga spp. Consider micro-aerophilic bacteria such as Campylobacter spp. and Helicobacter spp.  And don’t forget about exotic organisms such as Brucella spp.  Even then, this list is by no means exhaustive, and I am sure there are others that you have come across that I have forgotten about!

What can the lab/clinical microbiologist do to narrow the differential down and manage accordingly pending plate growth?

A few things come to mind:

Aerobic or anaerobic bottle positive?: If the aerobic bottle only is positive it can point to non-fermentors like Burkholderia spp. If the anaerobic bottle only is positive, then one must think about anaerobes (e.g. Bacteroides spp. Fusobacterium spp. )

Gram stain appearance: A cocco-bacillary appearance should make one think of Haemophilus and Brucella. Longish, pleomorphic spindle-shaped organism on Gram point towards Capnocytophaga. “Seagulls” or “squiggles” should send you in the direction of Campylobacter/Helicobacter

Patient History: A history of dog bites/exposure should make one think of Capnocytophaga. A prosthetic valve or other valve disease, or clinical stigmata of endocarditis can indicate a HACEK organism. A history of injecting drug use makes one suspicious of Burkholderia cepacia. A travel history to an endemic area could make one think of Brucella spp. or Burkholderia pseudomallei. In a patient with neck pain and swelling, you don’t want to miss a Fusobacterium necrophorum. If the patient is frankly septic, you want to make sure they are getting covered for Capnocytophaga and Pasteurella.

Of course, all this is speculation, and our educated guesses may be completely wrong in the end. It is however important speculation… We want to make sure that the patient is being covered for the most likely and the most serious possibilities.

Taking another, but no less important angle, from a lab point of view it is essential that any slow growing Gram-negative organisms are worked up in a biohazard cabinet. Laboratory exposure incidents for organisms such as Brucella spp.  and Burkholderia pseudomallei are resource-intensive, stressful for the staff, and for the most part avoidable.

And sometimes the bugs just like to mock us, even make fools of us. Just recently, I was convinced a wavy Gram negative rod in (multiple) positive blood cultures from a patient was going to turn out to be a Campylobacter, only for it to finally be identified as a Helicobacter cinaedi… Wrong again!


“Workflow trumps Fancy Tests”

I happened to be visiting a microbiology lab in a large teaching hospital last year. We were shown all the assays they used to rapidly identify a pathogen from positive blood cultures: PCR assays, FIuorescent In-Situ Hybridisation (FISH). They had the works!

The range of tests available was very impressive, and would be the envy of most diagnostic microbiology laboratories.

But there was a catch… At 8pm in the evening, the microbiology department shut up shop and everybody went home. The blood culture analyser stood there completely untouched until 8am the next morning, including any bottles that flagged positive during this time.

So a blood culture that went positive at 9pm would be sitting in the analyser for at least 11 hours before any attempt was made to identify the pathogen.

This got me thinking!

It actually doesn’t matter that much how many fancy assays you have, or how much money your laboratory has. If you can’t get your workflow right then it all becomes a bit academic.

I am a big proponent of 24/7 staffing of microbiology laboratories, or at the very least the processing of positive blood cultures being done 24/7. It is after all one of the most important samples in the microbiology department. We have plenty of lesser importance!

Turnaround times generally don’t just include the actual analysis of the sample. More often than not, it includes storage time, transport/courier time, registration time, verification time, etc.

And then the final result has to be both received and acted on by a clinician. This communication step is also vitally important. There are so many steps, pre-analytical, analytical and post-analytical that contribute to the total turnaround time.

It is useful to do intermittent vertical timeline audits of your critical samples, to see where the delays are occurring, and then sort these out first before you consider fancy assays. And often such delays can be sorted without having to spend a lot of money. It might just be a case of relocating a blood culture analyser, or adding an extra courier run…

I am not against fancy assays, they have their place, but only as part of the whole process…


“Separating the wheat from the chaff”

For every two or three genuine positive blood cultures, there is usually one which represents skin contamination (in my laboratory at least). As laboratory microbiologists, we often need to make an assessment about the likelihood of this fact, in order to guide the clinicians.

The “offending” microbes are usually coagulase negative staphylococci, corynebacterium species, propionibacterium species, and bacillus species.

However the isolates listed above do not always represent contamination. How can we assess the likelihood of such an isolate being genuine?

The following factors should be considered:

  • Time to Positivity: A blood culture signalling positive after 10 hours is more likely to be significant than one which signals positive after 30 hours. Bear in mind though that some organisms, such as propionibacterium species, are going to take a long time to become positive whether they are contaminants or not.
  • Number of bottles positive: If both bottles in the set are positive for the same isolate, then this increases the chance of the isolate being genuine. However remember that sometimes there will only be one bottle in the set (paediatric blood culture), and some organisms will often only grow in one bottle (bacillus-aerobic bottle, propionibacterium-anaerobic bottle)
  • Other BC sets taken and whether they are positive: If 6/6 bottles from 3 sets are positive with a coagulase negative staphylococcus then start looking hard for a geuine infection. On the other hand if only 1 bottle out of 6 is positive, then chances of this being a contaminant are high.
  • Clinical details- Prosthetic material on board: Coagulase negative staphylococci, corynebacterium species, and propionibacterium species all love clinging to and infecting prosthetic material. Has the patient got a prosthetic joint, a pacemaker, orthopaedic metalware, a venous or arterial line, etc, etc. if they do then think twice before dismissing blood culture isolates as skin contaminants.
  • Clinical details- Immunocompromise: I was “stung” once with a Bacillus species in a blood culture, which turned out to be genuine, as the patient was immunocompromised. The clue was in the fact that the isolate was present in two separate blood cultures…

All of these points above are just pieces of evidence in the puzzle. I advocate a systematic approach to assessing the potential significance/insignificance of blood culture isolates. Even if takes a couple of minutes per blood culture, it can be potentially very rewarding.

Even better is to look at ways of reducing the contamination rate of blood cultures. This new device looks very promising, essentially reducing the contamination rate by “discarding” the first part of the collection (the blood culture equivalent of an MSU!). I would have thought that such a device could potentially save both time and money on both the clinical and laboratory side. If those funding silos could only be broken down, I would love to try it!