implications for patient management. This week I will move on to how to detect these enzymes in the microbiology laboratory and how patients will be managed from an infection control point of view.
The sample arrives at the lab and is plated onto agar. Depending on the growth and appearance (albeit red/white/ green/yellow/pink/brown or mucoid/clear/dry/crinkled) a skilled biomedical scientist will know what the likely bacteria are and what antibiotics to test them against.
Laboratory detection of carbapenemases is however not easy and requires a high degree of suspicion when looking at the bacteria. Any Enterobacteriaceae with one of the Big Five enzymes (KPC, IMP, VIM, NDM and OXA) can appear sensitive or resistant to carbapenems on conventional laboratory testing. Therefore these enzymes can be missed! Also, confusingly, not all carbapenem-resistant bacteria produce carbapenemase enzymes and not all carbapenemase-producing bacteria are resistant to carbapenems! So how the heck do lab staff detect them?
The goal is to detect the acquired carbapenemases (which are transferable) as these pose an infection control risk. To start with, the bacterium is screened to see if it is resistant to a carbapenem antibiotic. Ertapenem is commonly used and most likely to test resistant in Enterobacteriaceae, the group of bacteria which most commonly carry an acquired carbapenemase. However, Ertapenem is the least specific carbapenem antibiotic because it can easily be made resistant by other resistance mechanisms like losing a porin and acquiring an ESBL. Therefore testing resistant to Ertapenem does not necessarily mean the resistance is
actually caused by a carbapenemase enzyme.
Another problem with screening for resistance with Ertapenem is that most non-fermenters including Pseudomonas spp. are inherently resistant to Ertapenem regardless of whether they have a carbapenemase or not. If the biomedical scientists see non-fermenters on a plate they would also screen with Meropenem or Imipenem.
Once the lab staff know the bacterium is resistant to a
carbapenem, the presence of a carbapenemase needs to be confirmed with further tests. At present PCR is the most reliable. The reason PCR is not done on all specimens is that it is time consuming and expensive.
There are a number of chromogenic agars (colour change with the detection of enzyme) being developed to help with screening but at present none reliably detect all of the Big Five carbapenemase enzymes.
There is a big drive from Public Health England (PHE) to put systems in place to prevent transmission of these antibiotic resistant bacteria before they become a major problem in our hospitals. This has resulted in the publication of a toolkit for NHS Trusts to help them achieve this.
• NOT infected or colonised
• CONFIRMED infection or colonisation
• SUSPECTED infection or colonisation
NOT infected or colonised
Patients who do not have these bacteria require no further
CONFIRMED Infection or Colonisation
Patients who have a POSITIVE MICROBIOLOGICAL CULTURE for a carbapenemase producing bacteria from a clinical specimen or screening sample (see screening process below) at any stage during their admission to any hospital.
Best Practice Control Measures
Patients who have been an inpatient in a hospital abroad
Patients who have been an inpatient in a UK hospital known to have had problems with spread of carbapenemase-producing Enterobacteriaceae (currently not specified!)
Patients who have previously been colonised with carbapenemase-producing Enterobacteriaceae
Patients who have previously had an infection with carbapenemase-producing Enterobacteriaceae
Patients who have had “close contact” (PHE has not defined this term but family or household member is a good place to start!) with a person who has been colonised or had an infection with carbapenemase-producing Enterobacteriaceae
Initially these SUSPECTED patients should have the same
infection control management as for CONFIRMED infection or colonisation (see above) until screening results are known. If negative on screening, these suspected patients can be treated as NOT infected or colonised.
PHE Screening Process for Carbapenemase–Producing Bacteria
• Rectal swab with visible faecal material OR stool sample
• PLUS if the patient has been hospitalised in a country with a high prevalence of carbapenemase-producing bacteria within the previous 12 months, send swabs from any wound or device-related site (see part 1 for maps).
The PHE guidance states that once a patient has tested positive they should be screened on a weekly basis. It continues that even if the patient has a negative screening result they should NOT be moved out of isolation. Isolation should continue because screening tests are not perfect and previously positive patients can become positive again,
especially if given antibiotics. However, it does beg the question “why screen weekly, if it doesn’t affect infection control practise?”
Contact Screening and Management
If a patient has not been isolated in a side room and is found to have carbapenemase-producing Enterobacteriaceae then ALL contacts within the bays or wards in which they have been during this admission should ALSO be screened. This DOES NOT include household contacts or members of healthcare staff.
All contacts should ideally be isolated (or cohorted together if too many contacts for available isolation facilities) whilst awaiting results of screening samples. If initial screening tests are negative they should have repeat screens sent on day 2 and day 4 and if they remain negative in all three
samples they can then be managed as normal and the isolation or cohorting relaxed.
If a contact tests positive then they should be managed as a CONFIRMED infection or colonisation AND all of their contacts should be screened. For example, a patient in a 6 bedded bay has 5 contacts, who should be screened. If a contact tests positive and has previously been in another bay, then the patients in that bay should also be screened. This continues until all contacts are negative. Ultimately the numbers involved in screening will depend on how common the enzyme-producing bacteria are in the general population; potentially the number of patients needing screening can increase exponentially.
The patient and their primary care physician should be made
aware of the patient’s status and this should be declared if the patient is re-admitted to hospital. No further management is recommended after the patient is discharged from hospital although long-term care facilities are recommended to consider the risk of transmission within their environment.
Is implementation of the toolkit going to be easy?
In reality it is going to be very hard for healthcare staff to implement the Public Health England toolkit. Rectal swabs will not be popular with patients and there is no decolonisation therapy to offer them. Healthcare staff will also struggle as this is an additional test to perform and they may find there are not enough side rooms for all of these patients. This might feel like an impossible task but these bacteria are very difficult to treat and infections with them have a very high mortality (in excess of 50%). Therefore anything we can do to limit the spread is worthwhile.