In one of our latest offering, we show how a molecular method can speed up identification of bacteria in septicaemia by over two days. The FilmArray technique allows clinical lab staff to identify the bacteria in an hour with pre-packaged reagents and a plug-and-play analyser.
This has to be a batter way of meeting the needs of patients in country communities, than shipping them or their specimens to the big city hospital labs.
FilmArray works by targeting a series of bacterial gene targets from species of interest and running an array of triplicate PCR assays for each target. It is an amplification method, unlike MALDI-TOF, which is used in larger clinical labs to speed up bacterial identification from blood cultures. For country labs to benefit from MALDI-TOF, the specimen or bacterial isolate has to be referred to the city lab, which adds a delay to the process. In our series, FilmArray successfully identified the bacteria from country labs containing, and even coped with mixed cultures. In other words, it performed better than MALDI-TOF for the range of bacterial that cause infections in our regional communities. The quicker time to identification should translate into real improvements in choice of antibiotics and subsequent clinical outcomes.
Other options for country settings & elsewhere:
- FilmArray has been applied to rapid identification of bacteria in other sterile fluid samples.
- For those who’ve been following our Ebola stories, a FilmArray has been used in the recent EVD epidemic and its performance assessed.
- Further applications are appearing in the professional literature.
This interesting new technology is better than anything we’ve had for blood culture rapid ID by a country mile, but we need to be careful not to get too far ahead of ourselves. We have yet to demonstrate that the use of FilmArray for blood culture identification in country labs directly impacts clinical outcomes.
Expect more on better methods for country labs from the gnome factory in future.
Remember AIDA? She’s made a few appearances lately, most under the guise of clinical tropical medicine. But the first outing for this useful acronym was in connection with a clinical teaching unit on the management of septicaemia. Those notes will be handy if you miss out on today’s lecture (15:00hr, FJC LT, QEIIMC).
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Why make a drama out of a crisis when you can turn in into a proper opera? The particular crisis the μGnome is concerned about here is the one that sucked him into μGnostics in the early days; the one that travels under a series of guises and that is variously known as septicaemia, systemic infection, blood poisoning, bacteremia and (for the four letter acronym fanatics) SIRS.
Before the days of high-tech medicine, the doctor had to hitch up his waistcoat as he bent over the patient to feel their sweaty brow and feel their thready pulse. There was weighty certainty in his prognostications as he proclaimed an imminent fever crisis. He might not have been able to tell you what the microbial cause of the infection was (μGnosis, or ætiology) but, by golly, he could make it all sound very grim.
The difference now is that we are no longer willing to wait for diagnostic certainty if it is at the price of increasing mobidity or risk of death. Septicaemia remains a potentially fatal condition, even in the best equipped centres. The diversity of potential infective agents will keep the attending physician guessing until we have faster, more accurate decision support tools. And a series of non-infective conditions may be mistaken for sepsis.
Which brings us to critical decision points: in a previous study we discovered almost by accident that if you performed a blood culture on the day the patient arrived in hospital there was a significantly lower mortality rate than if you delayed blood culture until the next day. We interpreted this incidental observation to mean that thinking about septicaemia early in the piece probably means you do something about it like start IV antibiotics earlier. In other words, it implies that there is a critical decision point somewhere in that first few hours after hospital admission. The clever people who are working up molecular tests to tell us exactly what the μGnosis is shortly after the patient arrives with a fever aim to exploit that crisis point. None of those new methods have quite made it over the line yet, so we have to make do with the good old blood culture for the time being.
Hence the opera, and not just any opera. The one that matters is AIDA. In this case the letters are an aide memoire for
Assess (the patient)
Inoculate (the blood culture)
Decide (how to manage the patient), and
Act (to start antibiotic therapy)
Specific skills need to be mastered in the correct use of blood cultures as part of the clinical investigative repertoire. These are summarised below in a Medical Interns talk. The part that the μGnome regrets cannot be provided on-line is the practical task of performing a blood culture. That is something practitioners will have to practice themselves. Happy bug hunting.
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Etiology of illness in patients with severe sepsis admitted to the hospital from the Emergency Department. Heffner AC, Horton JM, Marchick MR, Jones AE. Clinical Infectious Diseases 2010; 50: 814-820.
Heffner and colleagues took a look at how the ‘sepsis detectives’ perform in the challenging setting of a busy Emergency Department.
“Clinicians understand that sepsis is often a challenging diagnosis to establish at the bedside. Our report provides data supporting this assertion -namely, that in clinical practice ˜1 in 5 patients with suspected sepsis at admission may actually have a noninfectious disease that mimics the presentation of sepsis.”
This observational study of 211 patients admitted to an Emergency Department for severe sepsis, included 95 (45%) with positive blood cultures. Those with positive cultures were more likely to have vascular lines, and to have been in residential nursing homes. They also had a shorter time to antibiotic therapy in the ED. 44% patients with negative cultures had a clinical infection and 32% has a non-infectious disease that mimicked infection.
When the μGnome’s colleagues chewed the cud over this paper they highlighted a series of points:
- “sepsis” was categorised according to predefined criteria
- the study was in a single hospital centre between 2005 and 2007
- surgical patients were excluded from the study
- the focus was on very sick patients, possibly reflected in the relatively high mortality rate
- the timing of blood culture in relation to ED admission was unclear
- blood culture inoculation volumes and preliminary result turnaround was not reported
The μGnome agrees with the study’s authors. Working out who has an infective cause of severe sepsis syndrome is difficult in the ED.
- While early clinical intervention offers the best chance of preventing further deterioration, it is more difficult to identify a specific disease process.
- It is even more difficult to identify the causal infective agent with any degree of certainty.
- Pressure on ED staff to move patients on before an arbitrary deadline places the front-line clinician in an invidious position. A
- follow-up, prospective study including rapid molecular methods would be interesting.
One of the recurring problems in this area of clinical practice is the circular arguments that stem from the lack of a true reference standard for systemic infection. Blood culture is not, despite assertions in its favour, a ‘gold standard’:
- Many positive blood cultures from EDs contain possible skin bacteria that could easily have contaminated the culture during collection from a severely ill patient.
- False negative results may also occur as a result of prior antibiotic therapy, intermittent showering of bacteria into the peripheral circulation, or from inoculation of too small a quantity of blood.
These issues are likely to provoke further debate when we try to understand what a positive peripheral blood PCR assay means in the absence of a positive blood culture. The concept of a micrognosis was mentioned previously – this concept may help us find a way out of this circular diagnostic dilemma.