The phone started to vibrate at midnight and the Microbiologist groaned. Who would be ringing at the witching hour on Halloween? Then he started to worry… would it be safe to answer? Would there be some crazy person on the other end? Was it a vicious axe murderer? Then he remembered this was just the scary film he had watched before going to bed and he was actually on call for the hospital.
 
The person on the other end turned out to be the Emergency Department Registrar (certainly crazy for working Halloween in the ED…!)
 
“I’ve got a patient who has been bitten on their hand by a bat and I wondered what antibiotics we should start. We have guidelines for dog, cat and even human bites but nothing for bats.”

When I was a Registrar I was lucky enough to do an MSc in Clinical Microbiology at Queen Mary’s University of London. This involved a really early morning once a week to catch a train from Nottingham to London, a two hour journey, a day of practical work and lectures, and then a two hour journey home (it was a gruelling day, gosh I was so lucky!). I learnt a lot doing the MSc and met some great people, but it was during these long train journeys that I came up with an idea about how to pass essay and short note exams. This method became known as the Seven Pillars of Waffledom, but more on why later.
 
How do you help your examiner mark your essays and short notes?
Now this isn’t about cheating! It’s just a polite observation. During the MSc we had to write essays and short notes on various topics, it was good practice as this was also the standard format of the three hour exam papers in the “olde” FRCPath Part 1 exam; I  quickly realised I had to get better at writing essays and short notes. I spoke to my Consultant Supervisors who used to mark these exam papers and they all said the same thing, “make sure your answers are clear and easy to read”. “Is that it?” I replied grouchily. Simply put yes it is, because if you write clearly and legibly your examiner is more likely to look favourably on your essay and may give you the benefit of the doubt with some of your answers. If your answer is illegible and disorganised or if it takes too long to decipher your answer, then they will not be so kind and you won’t get the mark. How long do you think it takes to read an essay and how long extra should they allow to read a badly written one?! This may seem unfair but it is human nature… it’s also a good lesson for clinical work, good communication is really important and that includes your written communication.

​Another important lesson for me was that these essays and short notes usually involved closed marking; that is the examiner had a specific list of points they were looking for in the essay or short note. So you could wax lyrical about whatever you liked but if you didn’t put down the key points they were looking for you would get no marks.
 
So how do you write an essay or short note that hits those keys points and helps your examiner mark a question?
 
My solution was to write under headings in a report format rather than giving pages of prose. I would then use either short paragraphs or bullet points to make each individual point. In this way I was helping my examiner to see everything I knew without burying it in long paragraphs of text. I also didn’t waste time trying to work out how to beautifully structure my sentences or link my paragraphs into a long unnecessary story. It was purely factual. And if I did put down a piece of information they didn’t want to see they could go past it quickly and get to what they did want to see.
 
In order to do this I needed to know what my headings were for each essay before I wrote it; and this didn’t mean “acquiring the question” before the exam! What I needed was a clear essay plan that I could “learn” before I actually took the exam. But surely one size doesn’t fit all?! I hear you cry…

​Essay and short note plans
As you look at past exam papers you start to realise there are only a limited number of types of question you can be asked. The subject can vary but the types of essays repeat. This is a really important thing to realise as it means you only need to be able to remember a small number of “essay types” into which you slot your knowledge at the time of writing.

Let me explain with the original “seven pillars” I came up with which I could then write some knowledge or waffle about. For example, if you are asked to write an essay or short notes on a particular bacterium there are seven headings you should write under including the kind of things to write in each section:

1. Microbiology – describe the bacterium, Gram reaction, important biochemistry
2. Epidemiology – where do you find it, what infections does it cause?
3. Pathogenesis – how does it cause infection, what are its main virulence factors?
4. Laboratory Diagnosis – how is infection diagnosed, how is the bacterium identified?
5. Clinical Manifestations – how does infection with this bacterium present?
6. Treatment – how are the infections treated?
7. Prevention and Control – vaccination, prophylaxis, infection control procedures, public health

 
If you were to cover all of these aspects of a particular bacterium in an essay or short note then you would score very highly. Try it; using E. coli or Staphylococcus aureus apply what you know to this structure and see how it fits.

​Why seven headings?
​Because short lists are easier to remember than long lists and seven is often considered the optimum number of things we as humans can easily remember (although I did occasionally stretch the number to eight or nine if needed).
 
You can produce these types of plans for any infectious organism; bacteria, fungus, viruses and parasites. You can also then expand it out to antimicrobials, antimicrobial resistance and clinical scenarios.

So that’s the easy bit, what about other essay types?
I think the breakthrough for me came when I realised that what appeared to be more complicated essays were in fact all very similar, and standard essay plans could be adapted to help answer more difficult questions.
 
For example an essay might ask you to explain how you are going to investigate an outbreak of a specific infection such a Hepatitis C on a dialysis unit. Argh panic where to start!!! OK calm down… the essay plan might look like this:

1. Establish case definition
2. Confirm cases are real
3. Confirm outbreak and determine extent
4. Examine descriptive epidemiological features of the cases
5. Generate hypotheses
6. Test hypotheses
7. Collect and test environmental samples
8. Implement control measures
9. Interact with the press and write a report

A more detailed example of how this works for a specific essay on a Pseudomonas aeruginosa outbreak can be found here.
 
Now what if the essay said “you are a new consultant and the Chief Executive of your Hospital tells you the rate of Clostridium difficile is too high and he wants you to write a report saying how this should be tackled”. Argh! Don’t panic… On the face of it this might appear a different question but when you break it down your “outbreak” essay plan still applies:

1. Establish case definition – what is C. difficile and how are cases diagnosed, what constitutes a case?
2. Confirm cases are real – how will you test for C. difficile and confirm cases?
3. Confirm outbreak and determine extent – initiate a surveillance program to detect cases
4. Examine descriptive epidemiological features of the cases – look at surveillance data and undertake root cause analysis of cases to see if there are common factors
5. Generate hypotheses – based on common factors devise a plan to tackle those factors which appear to be driving C. difficile cases e.g. antimicrobial use, poor infection control practices, etc.
6. Test hypotheses – continue surveillance to look for reducing levels
7. Collect and test environmental samples – store patient samples for cross comparison if required
8. Implement control measures – factors shown to be successful should be expanded out through the hospital, and teaching and education undertaken to make this common practice
9. Interact with the press and write a report – present the findings of the new program to the Trust and ensure good practice becomes embedded in the Trust philosophy

 
So there you have my secret to writing essays and short notes. You still have to do the book work to know the facts to write down, but this method helps you make the best use of those facts. And I think it works.

​Whilst revising I read various books and papers to gain knowledge but I made sure every day that I read and learnt the essay and short note plans. I had them printed on post cards and in spare moments I would quickly read through them. The evening before and on the day of the exams when everyone was trying to cram in those last morsels of knowledge, I sat and read through my plans.
 
When I sat down with my exam papers I read all of the questions before starting and decided which questions I was going to answer. I then ordered them from easy to difficult and started with those I considered easiest to get some marks under my belt as well as give me more confidence and time to tackle the harder ones. I then picked my first “easy” question and jotted my “seven pillars” in the margin. I then started writing.
 
Here’s a big tip!
If I couldn’t think of anything to write under a heading the first time through I would just write the heading, leave at least half a page, and then come back to it at the end; I could usually by this point write something even if it was just “there is no vaccination against x, there is no role for prophylaxis and there are no specific infection control precautions”… it might be worth a mark or two?! On one occasion I was struggling to remember how we diagnose Cryptosporidium spp. infection, but I had time to come back to the blank space on the page, in my mind I went around the enteric lab “looking” at all of the equipment and “asking” why it was there. When I got to the UV microscope I remembered, Cryptosporidium spp. are acid fast and we used an auramine stain to detect it… Bingo! I filled in the space I’d left.
 
So finally why did this become known as the “Seven Pillars of Waffledom?” Well I was explaining my “original seven headings essay plan” approach to a friend on the MSc when she said, “oh like the 1922 book Seven Pillars of Wisdom by T.E. Lawrence (of Arabia)!” I said “kind of…but I think sometimes I may waffle more than provide wisdom!” She laughed “oh so you’re saying it’s the microbiological Seven Pillars of Waffledom, which will help me pass the MSc and my FRCPath exams!?” It wasn’t long before the “Seven Pillars of Wisdom” became permanently the “Seven Pillars of Waffledom” and the name stuck. (Editorial note: David can waffle on pretty much any topic, as long as he has a structured plan!)

Whatever you want to call them, here (these print to postcard size 4x6 inches) are the different types of essay and short note plans I came up with, and I hope they are as useful to you as they were to me. Incidentally, I also wrote Microbiology Nuts & Bolts in the same way using standard and consistent headings for each type of section (under editorial guidance!) so it is easier to remember the facts in the book.

1. Microorganism Essay Plans
2. Antimicrobial Essay Plans
3. Clinical Scenario Essay Plans
4. Diagnosis Essay Plans
5. Public Health Essay Plan – vaccination
6. Estates Essay Plan – department design
7. Outbreak Essay Plans

Looking down the blood cultures list whilst prioritising what needed phoning out first the Microbiologist noticed a blood culture positive on day 3 with a Gram-positive bacillus in the aerobic bottle only. Normally this wouldn’t provoke much interest as most pathogens grow within 12-24 hours and most Gram-positive bacilli are skin contaminants (Corynebacterium spp. and Cutibacterium spp.). However these were unlikely in this case: Corynebacterium spp. normally grow faster than this and would be in both bottles whereas Cutibacterium spp. although anaerobes tend to grow much slower. The clinical details just said “fever” (not overly helpful!) and considering the sample was 3 days old already, it didn’t seem that urgent, so the Microbiologist put it to the bottom of the list and got on busily calling out all of the Gram-negative bacilli and Gram-positive cocci, as these were more likely to be significant.

​Having cleared all the other positive blood cultures the Microbiologist came back to the Gram-positive bacillus. Looking up where the patient had been on this admission showed the blood culture had been taken in the Emergency Department, the patient had then briefly gone to the medical admissions unit before being discharged later the same day. Not much to go on there then. Maybe it wasn’t going to be significant after all.
 
Out of curiosity the Microbiologist then decided to check if the patient had been in before. This threw up something unexpected. The patient had had multiple attendances to the haematology ward as well as the outpatient clinic. Pulling up the clinic letters showed that the patient actually had chronic lymphoblastic leukaemia (CLL) and would therefore be immunosuppressed. This changed the situation; the blood culture could be an opportunistic pathogen and not a contaminant at all, muttering to himself, “chronic lymphoblastic anaemia is significant info for the specimen request card, when will they learn!” the Microbiologist decided to phone out the result straight away.
 
Still cursing healthcare staff who don’t fill out request forms with adequate clinical details, the Microbiologist bleeped the Haematology Registrar to find out more…
 
It turned out that the patient had presented to the Emergency Department with a fever and shortness of breath. The fever settled and the blood tests showed the patient wasn’t neutropaenic. The blood cultures had been taken before the blood test results came back. A dose of Piptazobactam had also been given in case the patient had febrile neutropaenia but this had been stopped when the neutrophil count was shown to be in the normal range. “As the patient was feeling better they were allowed to go home”, the Registrar said a little sheepishly knowing something was amiss if the Microbiologist was “showing concern”.
 
“Mmmmm…” said the Microbiologist to himself, “a blood culture positive on day 3 with a Gram-positive bacillus in the aerobic bottle only”… “Mmmmm…” he said again “this could be Nocardia”. The Microbiologist suggested getting the patient back in for a review whilst the laboratory tried to identify the microorganism. By the time the patient had been reassessed the organism had a name, Nocardia farcinica.

​What are the Nocardia spp.?
Nocardia spp. are a group of aerobic Gram-positive bacilli which do not take up Gram’s stain very well and so appear as long beaded Gram-positive bacilli. They have some mycolic acid in their cell wall, as a result they can be stained using a modified Ziehl-Neelsen (ZN) stain. The modified ZN stain uses 0.5-1% acid-alcohol as a decolouriser rather than the normal 3% used for Mycobacterium spp.  
 
Nocardia spp. live ubiquitously in soil, water and organic material within the environment. They are found worldwide.
 
On culture Nocardia spp. are slow growing, taking 2-3 days to produce typical colonies which look a bit like small fungi with hyphae. In fact early Microbiologists thought they were fungi and hence named all of the similar organisms to Nocardia spp. the Actinomycetes (a mycete is a fungus). They are bacteria though.
 
There are over 80 species within the Nocardia genus but the most common causing human disease include:

• Nocardia asteroides
• Nocardia farcinica
• Nocardia nova
• Nocardia camea
• Nocardia braziliensis
• Nocardia otitidiscaviarum
• Nocardia cyriacigeorgica
• Nocardia abscessus

 
How does infection with Nocardia spp. present?
The most common presentation of infection with Nocardia spp., known as nocardiosis, is with pneumonia, lung abscesses and lung cavitation. This is because the bacteria are most commonly acquired by inhalation. People with a normal immune system usually clear the bacteria but immunosuppression, especially defective cell mediated immunity, predisposes to this opportunistic pathogen. The most common immune problems include prolonged steroid use, haematological cancer, chemotherapy, organ transplantation and Human Immunodeficiency Virus infection.
 
Occasional infections occur in skin and soft tissue following contamination of wounds e.g. soil inoculation of a thorn injury or an animal or insect bite. In this case cellulitis or superficial abscesses are the most common presentations.
 
With pulmonary infections, infection spreads from the lungs via the blood stream to any body organ, but especially the brain where the bacteria cause abscesses; this is more common with N. farcinica than other species. Untreated pulmonary infections sometimes erode through the tissues of the thorax to discharge onto the chest wall through sinuses.

How is nocardiosis diagnosed?
Nocardiosis is diagnosed through the culture of Nocardia spp. from normally sterile sites. Identification of the bacterium used to be a bit of a nightmare and was based upon colonial appearance on agar, Gram appearance, modified ZN and unreliable biochemical methods. Nowadays MaldiTOF and PCR are excellent and reliable ways of identifying this bacterium.
 
If someone is suspected of having nocardiosis then further imaging is required, especially of the thorax. It is worth talking directly to the Radiologists to find the best modality for investigating. In my experience CT is often useful but I’m not a Radiologist. Confirmation of infection usually requires sticking a needle into the suspected site and aspirating pus for further laboratory testing; again this is often conducted by Radiologists.
 
Any immunocompromised patient with cutaneous or pulmonary infection should also have a brain scan to look for dissemination.
 
How is nocardiosis treated?
The treatment of nocardiosis can be difficult. It is important to test the individual bacteria for antimicrobial sensitivity as they are not always predictable. There is no national or international standard method for doing this but both Etests and broth dilution are suitable.
 
The species of bacterium is also important as some are more resistant than others e.g. N. farcinica is usually resistant to 3rd generation cephalosporins such as Ceftriaxone as well as Imipenem. Source control is also important, including drainage of abscesses and debridement of infected tissue wherever possible.
 
Trimethoprim-Sulfamethoxazole (Septrin) is the usual first line treatment with other agents added as required. Empirical first line treatments include:

Duration:

• Pulmonary 6-12 months
• Immunocompromised or disseminated ≥ 12 months
• For severe infection or disseminated disease IV antimicrobials should be continued for at least 6 weeks at which stage the patient can be converted to orals
• Cutaneous 3-6 months

 
Once sensitivities are known patients on three agent regimens can be converted to two agent regimens.
 
If there is no improvement within 2 weeks of starting treatment then the patient should be reviewed, further source control undertaken and consideration given to changing the antibiotics to alternative agents. Other antibiotics shown to have activity against some Nocardia spp. include: Co-amoxiclav, Ceftriaxone, Ciprofloxacin, Clarithromycin, Linezolid, Minocycline, Doxycycline and Tobramycin.
 
Monitoring
It is important to keep a close eye on these patients to look for disease progression as well as treatment toxicity. The most important toxicity is bone marrow suppression from the prolonged Trimethoprim-Sulfamethoxazole treatment. At least fortnightly full blood count, Urea and electrolytes and liver function tests should be checked. In addition further imaging is often required; some experts repeat imaging at 1, 3, 6 and 12 months of treatment and then 6 and 12 months after treatment to ensure there is no relapse.
 
With early diagnosis and targeted antimicrobial treatment the long term survival is 90%.
 
So our patient was brought back into hospital and reassessed. A CT scan of their chest showed a number of cavities however the scan of their head was normal. They were started on IV antimicrobials and by two weeks had started to improve. The patient was advised it was going to be a long course of treatment, the Microbiologist returned to the list of blood cultures to see if he could “intervene”, or more accurately “meddle”, with any other patient and their unsuspecting Registrar!

I am really fortunate to work with a great team of diagnostic cardiologists who have a keen interest in infective endocarditis. We have an endocarditis multidisciplinary team and do a ward round of all the endocarditis patients every week, regardless of where they reside in the hospital. One of the big problems for these patients is the long courses of IV antibiotics in the current treatment guidelines, be they British, American or European. As a result patients have long periods of time where they have central venous catheters (CVC) for administering the antibiotics and prolonged hospital stays; both predisposing to further infections.

​So when I saw an article in the New England Journal of Medicine from Denmark investigating whether oral antibiotics can be used in the treatment of this infection, my attention was stirred and I made the most of the present moment and ordered the paper from the library, “carpe diem”.