When I first started in microbiology, tuberculosis was diagnosed in the laboratory using Lowenstein-Jensen media poured as slopes in square glass flasks. These were incubated in a dedicated room about 4-5m square with floor to ceiling racks to hold the bottles. Culture took up to 12 weeks before a sample could be declared negative, and Mycobacterium tuberculosis usually took 8-10 weeks to grow. Full identification and sensitivities took a further 4-6 weeks to come back from a reference laboratory. What a nightmare!? Not to mention the chaos that ensues when someone drops a glass bottle full of tuberculosis which then shatters all over the laboratory floor…! Not a great scenario I can tell you.
Imagine how frustrating it was to have to start patients on anti-tuberculosis treatment without knowing whether they actually had TB or not. Tuberculosis treatment is usually 2 months of Rifampicin, Isoniazid, Ethambutol and Pyrazinamide, followed by 4 months of Rifampicin and Isoniazid. With the old method of diagnosing TB the patient could have been 4 months into a 6 month treatment regimen before either the diagnosis was confirmed or, even worse, excluded! I cringe at the kind of conversations that might have taken place… “Well Mrs Smith, the good news is you don’t have TB, the bad news is that we have been poisoning you with 4 different hepatotoxic drugs for the last 4 months and we still don’t know what’s wrong with you…!” It must have been really embarrassing.
So how does liquid TB culture work, why has it changed the way we diagnose TB and why do I have it in my Top 3?
Liquid TB culture involves incubating the respiratory sample, other tissue or fluid in a liquid media designed to support the growth of Mycobacteria spp. This takes place in a small test tube inside an automated incubator. The tube also contains an indicator system that allows the incubator to know when a Mycobacteria spp. is growing. In the context of the Becton-Dickinson MGIT system this is a gel in the bottom of the tube which contains a fluorescent molecule that is suppressed by oxygen. As the Mycobacteria spp. grows it uses up the oxygen and the molecule is able to fluoresce. The incubator scans the tubes every 60 minutes to look for increased fluorescence. Once the tube is positive it can be unloaded and stained to look for acid fast bacilli using auramine or Ziehl-Neelsen (ZN) stains.
Liquid TB culture is MUCH FASTER than the old fashioned Lowenstein-Jensen media method. Most Mycobacterium tuberculosis will grow within 2 weeks in liquid culture. This means that patients can usually wait for confirmation of the diagnosis before starting treatment. Sensitivities take about a week longer before they are available to help guide ongoing therapy. In fact what we tend to see now is the patients primary care physician sending a respiratory sample to the laboratory at the time they refer the patient to the TB clinic...as most patient are seen in around 2 weeks, the provisional result is already available. This is a much faster and safer way of managing patients and therefore it is number 3 on my list of Top 3 microbiology things that have improved patient care in the last 15 years.
At Number 2: MaldiTOF
Okay, at number 2 is the MaldiTOF. There is a bit of a joke in microbiology circles in the UK that Labs are divided into those who have MaldiTOF and those that want MaldiTOF. So what is it and why does everyone want one?
MaldiTOF stands for Matrix-Assisted Laser Desorption/Ionisation Time Of Flight and is essentially a form of mass spectrometry now used in microbiology laboratories to identify bacteria and some fungi. It’s amazing! It works by vaporising a small sample of bacteria with a laser and then introducing that vapour into a tube where electric charges and the size of the molecules released by the vaporisation affect how long it takes for the fragments of bacteria to move along the tube, ooh complicated! BUT essentially the number and size of the fragments produces patterns of peaks and troughs that are specific to each bacterial or fungal species. This pattern of peaks and troughs can then be compared to a database of patterns to identify the bacteria or fungus. All told it takes a few minutes for MaldiTOF to identify even tiny amounts of microorganism, and better yet, once you have the MaldiTOF there are no consumables so each test costs in the order of a few pence!
There is virtually nothing in regular day-to-day microbiology that a MaldiTOF cannot identify. Not only does this mean that there is much less need for laboratories to send microorganisms away to reference laboratories for further identification when the old methods failed (and let’s be honest, the old methods used to fail quite a lot of the time) but the turnaround time of these identifications is very fast. In my experience MaldiTOF has knocked about 48 hours off of the turnaround time of most specimens in microbiology laboratories meaning patients can be changed to specific treatments or inappropriate treatments can be corrected 48 hours earlier.
When MaldiTOF first became available I used to think that it would have its biggest impact on samples from “sterile” sites e.g. blood cultures, joint fluids and CSFs, etc. but these patients are usually already on effective empirical antibiotic treatments. Over time I’ve come to realise that the biggest impact is actually in large volume samples such as urines and sputums from patients, who may or may not already be on antibiotics. Here knowing the name of the bacteria can allow Microbiologists to predict sensitivities and correct treatments, e.g. Serratia marcesans, Morganella morgani and Enterobacter cloacae all have a chromosomal AmpC enzyme that makes them resistant to most beta-lactam antibiotics.
So MaldiTOF has increased the speed and accuracy of the identification of bacteria and some fungi in routine diagnostic laboratories, reducing the turnaround time of these results, improving our treatment of patients, and all in a cost effective manner. What more do you want? A MaldiTOF I guess! This is why MaldiTOF is number 2 in my Top 3.
Number 1: The Internet
So the Internet isn’t a microbiology specific thing, but in my opinion the Internet has probably had a bigger impact on medicine, including microbiology, than any other thing during my career. When I first started in medicine in the late 1990s the Internet was only just beginning to “take off” (it really is that recent!) and even then most connections where of the slow dial-up type. The concept of broadband connectivity which we take for granted in much of the UK today was only a dream; if you wanted to use the internet at home you had to use your telephone line and therefore no one could call you at the same time. Ha Ha, Remember those days!?! So why is the Internet number 1 on my list?
- Faster reporting of results – microbiology tests can now be reported electronically so that results are available to the requester on the same day the samples were tested whereas previously the requester had to wait for a paper copy of results
- Electronic empirical antimicrobial guidelines – these can be accessed on computers and smartphones making sure they are available at the time the prescriber needs them, whereas if the prescriber had to go and find a paper copy and there wasn’t one easily available they would make their own mind up about what to prescribe, or use an out-of-date version. Remember trying to up-date all those different versions, which were kept in all manner of places!?!
- Access to journals – it used to be the case that if you wanted to read a paper, or find some national or international guidelines from a journal, you would have to go searching through the hospital library to find that specific article. Nowadays you just have to go to the homepage of that particular journal and search for an electronic version to print out. This makes it much quicker and easier to find the information you want.
- Communication – previous communication between Doctors used to be by written letters as we have always been tricky to track down by telephone; the availability of email has allowed healthcare professionals to communicate in a much more timely fashion, including internationally
- Outbreak and warning alerts – the Internet allows for the rapid dissemination of alerts about outbreaks of infection with public health importance e.g. Ebola, as well as warnings about potential dangers with drugs or devices used in healthcare
- Off-site IT and laboratory technology support – in the past if a piece of laboratory equipment broke an engineer had to come out to look at the equipment in order to work out what had gone wrong, go away to get replacement parts and return again to finally fix the problem. Nowadays the same engineers can access the equipment’s software from somewhere else, work out what is wrong, either correct a software issue remotely or order the replacement parts before attending the laboratory. This means laboratory equipment tends to be repaired much more quickly...but there is less downtime for a cuppa!
- Teaching resources, sharing information and best practice – the Internet is full of fantastic written, audio and visual resources for learning, including about microbiology… just look at Microbiology Nuts & Bolts! ;-)
So it would seem that the Internet is the answer to all of our problems, but for me there are some significant dangers to the uncontrolled availability of information that the Internet brings
- Variable quality of information on the internet for patients and healthcare workers – there is no control over what is published on the Internet; individual websites have a degree of responsibility to ensure that what they publish is accurate but this is not mandatory. As a result it is important that any information is evaluated as to whether the person presenting the information is actually qualified to make that judgement and if there is any bias that might influence their information
- Increased potential for data protection breaches and accidental breaches of confidentiality – it doesn’t matter how good Internet security is there always seems to be someone who wants to break in to a secure database and steal information, including information about patients
- Online forums – allow easy, often anonymous access to anyone with an axe to grind to voice their dissatisfaction, which they may never express if face-to-face e.g. a doctor refuses to prescribe an antibiotic for a patient with a suspected viral infection, completely in line with best practice and NICE guidelines, and then the dissatisfied patient can go home, log on to the Internet, and publicly call in to question their competence.
- Expectation that everything should be available instantly 24 hours a day, 7 days a week! The Internet allows us to access anything we like online at any time we want and this has led to an expectation that everything should be available immediately, including healthcare; it’s not just patients who don’t want to wait for a few hours in Accident & Emergency or governments wanting 7 day working, but we as healthcare professionals are increasingly annoyed when we can’t have instant access to Specialist advice...I quite liked it slower!
So what do you think has made the biggest impact? I can hear people yelling “PCR should be on the list!” “What about my mobile phone!” “Chocolate!!!” Share your thoughts with others… on the Internet…. Hmmmm… do you see my point? It’s made the biggest impact for me.