“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!


“Perfect is the enemy of good (microbiology)”

This quote attributed to Voltaire (“Le mieux est l’ennemi du bien”), rings true to me. I have never been a perfectionist, and the idealistic pursuit of perfectionism can hinder real-life achievement and progress. 

The quote came back into my conciousness during the early days of the COVID pandemic when I listened to a great speech by Dr Mike Ryan from the WHO when urging countries to act quickly in the face of the rapidly developing COVID situation.

Of course, such a concept can also apply to the microbiology laboratory.. Here are a few examples:

Protracted work-up of samples: When a sample arrives into the microbiology laboratory, the clock is ticking. In relentless pursuit of isolating that fastidious bacterium, time passes by and before you know it a week has passed… The clinical usefulness of a microbiological result is inversely proportional to the time spent to produce it. In the hospital setting, the average length of stay is 3-4 days… Excessive time spent on certain samples is not only a waste of resources, it also generally does nothing for the patient. Get a result out, even if it is not the perfect one that you are striving for.

Excessive work-up of samples: The classic example of this is identifying every bacterial isolate in a mixture of enteric flora. For the most part, such an exercise is futile, even when isolated from a sterile site. Enteric flora isolated from sterile sites usually represent a source control issue, and who knows what the pathogen might be in the mixture, if any. Such practice is generally a waste of resources, and reporting individual isolates along with individual susceptibilities is time-consuming and often leads to poor antimicrobial stewardship. Working up bacteria within a mixture of enteric flora might be “technically perfect” but does little to help the patient.

Excessive testing protocols: A good example of this is stool samples arriving into the microbiology laboratory. There are many microbiological tests that one can do with a stool sample, culture, PCR for bacterial & viral pathogens, microscopy for parasites, C. difficile testing, the list goes on. However, to perform all the available tests on every stool sample in the hope of maximising the odds of isolating a pathogen would be incredibly expensive, but in most cases would do little to change patient management. Enteric testing should very much be tailored depending on what is on the microbiology request form.

I am sure there are many other examples that one could think of. Perfection in the microbiology laboratory is very much a pipe dream, and can actually be detrimental to good patient care. We cannot possibly hope to identify all potential pathogens in every sample and do it in a timeframe that is beneficial to the patient. We need to move past our fear of missing something…

When developing testing methodologies or reviewing individual patient samples, we should always be asking ourselves “By doing what we are doing, are we providing overall value to the patient?” 




“Antimicrobial Stewardship and the Problem of Unsolicited Advice”

“I would stop that fluoroquinolone…”

A good proportion of my job as a clinical microbiologist is being an antimicrobial steward. i.e. giving antibiotic advice based on microbiology results. And a good chunk of this advice is “unsolicited”, in that nobody has specifically asked for it. One could argue that the advice is “semi-solicited” in that it is given under the auspices or framework of an Antimicrobial Stewardship Program.

Being on-call over the Christmas period has made me reflect on the difference between giving solicited and unsolicited antibiotic advice. When someone specifically asks for your advice, they are genuinely interested in what you have to say and for the most part listen and act on your recommendations. However, when the advice is unsolicited, regardless of whether it is given by phone or in-person, it may not always be welcomed with open arms…

It is not that the prescriber necessarily disagrees with your advice. They know it is generally correct in purist terms. It is just that there are (several) other agendas at play for the attending clinician.

Taking it from the clinician’s perspective, antibiotic advice from an antimicrobial steward on occasion may prevent early discharge and may create logistical issues in terms of organising outpatient antibiotics, arranging further investigations, or arranging clinic follow-up. Put in simpler terms, more work. Such factors are accentuated during the Christmas break where the (laser) focus is on getting patients out of hospital, and minimising any admin work that is required during the holiday season.

A classical example of this is advising on a Staphylococcus aureus bacteraemia. (2 weeks IV abx, Echocardiogram, repeat blood cultures, etc.) Sometimes the attending clinician just doesn’t want to know…

Of course, sometimes our advice can be beneficial to the patient workflow & pathway. For example, early oral switches, and promotion of short course antibiotic therapy. I think it is really important to focus on documenting & highlighting such “wins”, as a counterbalance for when “bad news” needs to be given.

Personally, I am a little fatalistic when it comes to whether my advice is accepted, whether it solicited or unsolicited. I believe in the principle that the final management decision always rests with the attending clinician and they can choose whether to take my advice or not. There is only so much that you can do…

Building up relationships and trust is key in getting people to listen to your unsolicited advice. Some prescribers are more receptive than others. And some specialties are more receptive than others.

So, is unsolicited advice more about the giver than the receiver? Is it essentially self-serving in nature? Or is it a necessary evil of being a good antimicrobial steward? These are difficult questions, and ones that I do not have the answers for.

The other approach is to have a more passive approach to antimicrobial stewardship, to only give advice when it is specifically asked for, or at least to issue clear guidelines as to when advice should be sought.

My children often complain when I give them unsolicited advice on how to live their lives. I hope that my clinician colleagues do not feel the same way!


Check out this interesting article on the psychology of antimicrobial stewardship, published in CID