Advice

Technology overview

Technology overview

This briefing describes the regulated use of the technology for the indication specified, in the setting described, and with any other specific equipment referred to. It is the responsibility of health care professionals to check the regulatory status of any intended use of the technology in other indications and settings.

About the technology

CE marking

The BD MAX Enteric Bacterial Panel (EBP) is manufactured by BD Diagnostics and received a CE mark in March 2013. The BD MAX System, which is a platform needed to run the panel, received a CE mark in April 2011. Both the EBP and the BD MAX System are classified as Annex III devices and are in compliance with the European directive for in vitro diagnostic medical devices (IVDD/98/79/EC).

Description

The BD MAX EBP is an assay to be used on the BD MAX System. The BD MAX System is a fully automated real‑time polymerase chain reaction (RT‑PCR) machine that can process up to 24 samples at a time.

The BD MAX EBP is an automated in vitro diagnostic test that uses RT‑PCR for the direct qualitative detection of enteric bacterial pathogens. Targets include Salmonella spp., Campylobacter spp. (jejuni and coli), Shigellosis disease causing agents (Shigella spp. and enteroinvasive E. coli [EIEC]) and Shiga‑toxin producing E. coli in stool specimens from symptomatic patients with suspected acute gastroenteritis, enteritis or colitis.

The BD MAX EBP kit comprises all the reagents and components needed for extraction and PCR set‑up, including pipette tips. Kit components include:

  • Unitised reagent strips (24 strips for 24 tests) that allow a single strip to be used for a single test, thereby minimising waste and disposables. The strip contains a single reaction tube, a waste receptacle, and wash, elution and neutralisation buffers specific to the test. The strip is placed into the BD MAX System rack and the extraction and master mix tubes are snapped into the unitised reagent strip.

  • Extraction tubes (24 tubes for 24 tests), that contain magnetic beads and lytic enzymes needed to extract the sample. Extraction reagents are lyophilised and dried down for long‑term storage at room temperature.

  • Master mix (24 tubes for 24 tests) that contain primers and probes specific to the test and for the included Sample Processing Control. Reagents are lyophilised and dried down for long‑term storage at room temperature.

  • Septum caps (25 septum caps) that allow robotic pipetting through the cap with no need to de‑cap for sample processing.

  • Sample buffer tubes (24 tubes) that contain the buffer specific for the test.

Although the microfluidic cartridge is supplied separately from the BD MAX EBP kit; it is included in the price per test.

To run a test, the stool sample is homogenised and added into the sample buffer tube. This tube is placed into the BD MAX System, along with the BD MAX EBP reagent strip and microfluidic cartridge. Automated cell lysis, DNA extraction, amplification and detection all take place in the BD MAX System. A qualitative result for each run of samples is given in under 3 hours. However, results are available in under 2 hours if a small number of samples is run. The results indicate whether the sample is positive or negative for each of the pathogens that the test is able to detect. A message reading 'unresolved', 'indeterminate', or 'incomplete' denotes test failure.

The manufacturer states that the results should not be used as the sole basis for diagnosis and treatment or for other patient management decisions. Positive results do not rule out co‑infection with other organisms that are not intended to be detected by the test. In practice the test may be performed alongside culture methods and tests for other pathogens not tested for by the BD Max EBP.

A number of BD Max assay cartridges are available to run on the BD MAX System, and open system reagents can also be used for user‑defined protocols. Assays other than the BD MAX EBP are beyond the scope of this briefing.

Other CE‑marked devices that have a similar function to the BD MAX EBP include:

  • BioMeuriex FilmArray Gastrointestinal Panel

  • Luminex xTAG Gastrointestinal Pathogen Panel

  • RIDAGENE Bacterial Stool Panel and EHEC/EPEC Panels

  • FTD Bacterial Gastroenteritis (Fast Track Diagnostics).

Intended use

The BD MAX EBP is intended to identify common enteric bacterial pathogens in stool specimens from people with gastroenteritis.

Setting and intended user

The BD MAX EBP test is intended to be carried out in microbiology laboratories by appropriately trained staff. Stool samples collected from any care setting are sent to a local microbiology laboratory for testing.

Current NHS options

Gastroenteritis is usually self‑limiting. Therefore treatment normally only includes advice on rehydration to prevent serious dehydration, although in some cases antibiotic therapy, anti-diarrhoeal or antiemetic drugs are given according to the NICE clinical knowledge summary on gastroenteritis. Stool samples are sometimes analysed to identify the infectious agent causing the gastroenteritis and the clinical knowledge summary, which is designed for healthcare professionals providing primary healthcare, describes patient selection criteria for stool analysis:

  • people who are systemically unwell

  • people who have blood or pus in the stool

  • people who have an impaired immune system

  • people who have recently stayed in hospital or had recent antibiotic treatment

  • people with diarrhoea that has occurred after travelling abroad to certain countries

  • people with persistent diarrhoea in whom giardiasis is suspected

  • where there is diagnostic uncertainty.

The NICE guideline on diarrhoea and vomiting in children, which applies to children younger than 5 years presenting in any setting, recommends that microbiological investigation of stools should be done when:

  • septicaemia is suspected

  • there is blood or mucus in the stool

  • the child is immunocompromised.

Microbiological stool investigations should be considered when:

  • the child has recently been abroad

  • the diarrhoea has not improved by day 7

  • there is uncertainty about the diagnosis of gastroenteritis.

To enable the rapid detection and management of disease and epidemics, registered medical practitioners and laboratories in the UK have a statutory duty to notify their local health protection team when they diagnose certain 'notifiable' diseases (Public Health England 2010). This should be done orally, usually by telephone. It is recommended that this should always be done within 24 hours of the diagnosis. Urgent oral notification should be followed up by written notification within 7 days. Notifiable bacterial organisms associated with gastroenteritis include Campylobacter spp., Salmonella, Shigella and verocytotoxigenic E. coli (including E. coli O157).

Standards for microbiological investigations involving enteric pathogens are set out by the Standards Unit, which is part of Microbiology Services at Public Health England.

Microbiology laboratories testing faecal specimens look for a number of specific pathogens. The laboratory decides which pathogens to look for, based on a complex range of factors, including whether:

  • the specimen is from a hospital patient or a person being treated in primary care

  • an infectious disease outbreak is involved

  • the patient lives in the UK or has travelled to the UK from their home abroad

  • food poisoning is involved

  • the patient has a compromised or suppressed immune system

  • the patient is a child under the age of 5 years.

All diagnostic specimens (except when screening for a specific organism is requested) should be cultured using standard bacterial culture methods to identify Campylobacter spp., Salmonella and Shigella spp. and E. coli O157. Further tests may be added if necessary, and some specimens may need to go to a reference laboratory for strain‑type identification (Public Health England 2014).

Usually, samples test negative because these pathogens are relatively rare, even among people with gastroenteritis. Bacterial culture is recognised as having less than 100% sensitivity. PCR has a higher sensitivity, and can detect very low levels of pathogens in the sample. Therefore, more pathogens can be found using PCR than conventional bacterial culture, although the clinical significance of these additional pathogens may sometimes be uncertain (Public Health England 2014).

Some laboratories currently use PCR methods for detecting gastrointestinal pathogens. Guidance from Public Health England (2014) states that rapid diagnostic tests, such as PCR, should be considered for use, if available. In current practice, bacterial culture is done following a positive PCR result whereas a negative PCR test can avoid the need for bacterial culture of stool specimens.

The Health Protection Agency has produced guidance on the interpretation of PCR assays (Health Protection Agency, now Public Health England, 2013). If PCR was used to identify a notifiable infection, this should also be reported and local laboratories should confirm the result by culture when possible.

Identifying which enteric pathogen is causing gastroenteritis may not always result in a change of treatment but early detection or exclusion of pathogens, including the bacteria detected by BD MAX EBP, may reduce the length of stay or avoid the need for isolation. Identification may be used to monitor infectious diseases, for outbreak investigations, for epidemiological investigations and for surveillance. In some circumstances, such as for people with a compromised or suppressed immune system, pathogen identification may save lives because rapid identification of pathogens allows appropriate antibiotics to be given sooner. Early identification of pathogens may also prevent surgical intervention because gastroenteritis can mimic acute appendicitis.

Costs and use of the technology

The list price of the BD MAX EBP (including microfluidic cartridge) is £22.50 per test, excluding VAT.

The BD MAX EBP can only be run on the BD MAX System platform, which has a list price of £85,000, excluding VAT. A 1‑year warranty is provided on the BD MAX System. From year 2, the typical cost of a fully comprehensive service agreement, including annual preventive maintenance, is 10% of the purchase price (£8500). According to the manufacturer, the technology has not been on the market long enough to estimate its lifespan, but if the equipment fails within a typical 5‑year contract, the manufacturer would expect to replace it.

The BD MAX System can also be used to run other BD molecular diagnostic tests, which if used, may reduce the overall cost of adopting the BD MAX EBP test. Tests developed by other companies can also be run on the system. Examples include the Check‑Direct CPE assays (Check‑Points) for carbapenamases, currently distributed in the UK by Hain Life Sciences, and in vitro diagnostic tests produced by Diagenode. The BD MAX System is 'open', which makes possible for third parties to develop or optimise their tests to run on the system. Users can also put their own in‑house developed assays on the system to fully automate their testing process.

Likely place in therapy

The BD MAX EBP is used at the same point in the patient pathway as culture‑based methods for enteric pathogen identification. People would continue to give stool samples, according to the current criteria, at the same point in the clinical pathway in primary or secondary care.

Specialist commentator comments

One specialist commentator noted that a test that improves sensitivity and the speed of detection of potentially notifiable pathogens must be welcomed. However, because most of the pathogens detected by the BD MAX EBP do not have a specific treatment, the effect on the patient pathway is likely to be limited. Exceptions to this are outbreak settings or specific populations such as people with suppressed immune systems or the most seriously ill patients.

One specialist commentator stated that early detection or exclusion of a bacterial gastrointestinal pathogen can reduce the length of time spent in hospital and can help to avoid unnecessary investigations in people with gastrointestinal symptoms. They also felt that there may be some small infection control benefits from diagnosing bacterial gastroenteritis early. The commentator noted that a greater benefit may be seen from a rapid test that excludes all causes of infective diarrhoea, including viruses and parasites, rather than bacterial alone. A second commentator agreed that a rapid test for detecting viral gastroenteritis may be more useful.

Two specialist commentators noted that the BD MAX EBP used alone would not, or would very rarely, shorten the time the patient spent in isolation because the test does not detect all known pathogens or the most common pathogens. One specialist commentator stated that additional tests, including bacterial cultures, may be needed to provide a final comprehensive result and these cultures can delay clinical decisions. This commentator also noted that they would prefer PCR panels that detect a larger range of pathogens.

Two specialist commentators noted that the automated nature of the test means that it could be done by lower grades of laboratory staff, if biomedical scientists give appropriate training and help with data checking and trouble‑shooting. Therefore, although whole‑time equivalent staff numbers may not change, there is potential for savings through skill mix revision. A commentator noted that a disadvantage of BD MAX EBP (as with any PCR‑based technology) is that there is no means of providing antibiotic sensitivity data when using this technique. With increasing antibiotic resistance this information is essential to ensure appropriate antibiotic stewardship.

Equality considerations

NICE is committed to promoting equality and eliminating unlawful discrimination. In producing guidance, NICE aims to comply fully with all legal obligations to:

  • promote race and disability equality and equality of opportunity between men and women

  • eliminate unlawful discrimination on grounds of race, disability, age, sex, gender reassignment, pregnancy and maternity (including women post‑delivery), sexual orientation, and religion or belief (these are protected characteristics under the Equality Act 2010).

Identification of enteric pathogens is recommended for people who have a compromised or suppressed immune system. This may include people who are considered to have a long‑term condition if that condition has a substantial effect on daily activities to the extent that it causes disability. Disability resulting from long‑term conditions is a protected characteristic under the 2010 Equality Act.