“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?” 

Michael

 

 

“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!

Michael

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

“The return of the fried egg”

After a prolonged COVID-induced hibernation, Mycoplasma pneumoniae is back in NZ. Over the past couple of months there have been a sprinkling of cases throughout NZ picked up on respiratory panel testing by PCR in diagnostic laboratories, including my own.

I can hardly remember the last time I saw a Mycoplasma pneumoniae infection. It was definitely pre-COVID. The low Ro of Mycoplasma pneumoniae infection meant that transmission was brought to an almost instantaneous halt by the introduction of Non-Pharmaceutical Interventions (NPIs or “lockdowns”) following the emergence of the COVID pandemic.

Over the past year or so, it has started making a comeback worldwide. It has taken longer than other pathogens to return post-COVID, and as described in this interesting article in the Lancet, this is likely due to various factors such as the slow generation time (6 h), long incubation period (1–3 weeks), and relatively low transmission rate of Mycoplasma pneumoniae. It has returned later than most in New Zealand, likely due its geographical isolation and relatively sparse population.

In a (slightly perverted) way I am glad it is back. It is a very interesting bug! It is one of the smallest known bacteria, at only 300nm. It lacks a cell wall, which is why you cannot see it on a Gram stain. It is also why Mycoplasma infections do not respond to beta-lactam antibiotics. It most commonly causes respiratory infections but also has the ability to affect a wide range of organ systems, either by direct invasion or autoimmune reaction. This is eloquently summarised on this table.

It is sometimes referred to as a cause of “walking pneumonia” which can be a little misleading as it is certainly well capable of causing hospitalisation in both adults and children.

As for the “fried egg”, this refers to its phenotypic appearance on culture media (e.g. Hayflick media). Of course, fried eggs have not really returned as virtually nobody these days (and certainly no diagnostic labs in NZ) culture for Mycoplasma pneumoniae, with the mainstay of diagnosis now being PCR and to a much lesser extent, serological testing. Having said this, there is some evidence that Mycoplasma serology is more sensitive than PCR, likely due to delayed presentation to Health Services.

With the worldwide resurgence of Mycoplasma pneumoniae, the other thing to consider is whether the re-emerging strains are macrolide resistant.  This is difficult, due to the lack of laboratories culturing for Mycoplasma pneumoniae. However, assays are now being developed to look for the key rRNA mutations coding for macrolide resistance directly from clinical samples. It is certainly something we will need to think about both from a treatment and surveillance point of view.

Which is the optimal sample type for (molecular) diagnosis of Mycoplasma pneumoniae? There does not seem to be a lot of literature on this topic and it probably depends on the clinical presentation of the disease. If presenting as an upper respiratory tract infection, which it can do, then throat or nasopharyngeal swab is likely to be best.  For pneumonia then sputum or BAL are probably optimal.

So, Mycoplasma pneumoniae is back, and because of this, we need to start thinking about it again as a differential diagnosis in our patients. Its return has however, made my job a little more interesting…

Michael