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Contending with CPE: The story so far

It is almost one year since a public health emergency was declared over the spread of carbapenemase-producing Enterobacteriaceae (CPE) in the Irish health system, with Minister for Health Simon Harris citing a “worrying and rapid increase” in incidence when making the announcement on 25 October 2017.

CPE, which disable carbapenem antibiotics, aka the ‘drugs of last resort’ for life-threatening infections, are challenging health systems globally.

Irish microbiologists have emphasised that managing the spread is time-critical, and in March 2017, leading figures in the specialty described the situation as a national emergency that was spiralling out of control (‘Ireland at CRE crisis point’, Medical Independent (MI), 27 March 2017).

However, critical resourcing has been slow to materialise, if at all. Also, there is no specific budgetary line for management of CPE/healthcare-associated infections (HCAI) in the HSE National Service Plan 2018.

As reported by MI in July, an internal, high-level HSE memo issued by the then Director General Mr Tony O’Brien on 26 April 2018 warned that “clarity” was still awaited from the Department of Health around funding to combat the rise of CPE.

Nevertheless, the Department maintains it has “held back” an unspecified amount of “dedicated funding for 2018” and that the HSE has prioritised work programmes for this funding in line with the CPE risk, which also addresses strategic interventions in Ireland’s National Action Plan on Antimicrobial Resistance 2017-2020 (iNAP).

According to the Department’s spokesperson, there has been “significant progress” in relation to CPE management and resourcing in a number of areas since the establishment of the National Public Health Emergency Team (NPHET) on 2 November 2017. These areas include enhanced surveillance; HSE Implementation Team reports and key performance indicators in the HSE Service Plan; increased infection prevention and control capacity via approval for funding for a number of posts; and publication of a suite of Expert Group guidance documents.

Since 31 May 2018, the HSE, with support from the Department, has authorised Hospital Groups to commence recruitment of additional laboratory staff to enhance detection of CPE.  “Better detection of CPE is a critical step in controlling spread of CPE.  The HSE has also committed resources to enhance reference laboratory services to support tracking of spread of CPE,” says a HSE spokesperson.

According to minutes of a meeting of the Health Protection Surveillance Centre (HPSC) CPE Expert Group in June, “a budget of up to €2 million per annum has been approved to spend on laboratory staff and clerical staff only. This is to be initially spent in hospitals where outbreaks have occurred, who are approved to recruit now.” The minutes added: “It was noted that the annual cost for screening for CPE was budgeted to cost €5.5 million. These estimates have been provided to the Department of Health.”

The minutes also reported that Prof Martin Cormican, HSE Clinical Lead on HCAI and Antimicrobial Resistance (AMR), was working on estimates for managing CPE, with a two-to-five-year plan to be submitted to the Department in October.

In late March, Prof Cormican told a meeting of the same group that “we are continuing to see substantial numbers of newly detected patients” with CPE. In May, Prof Cormican also informed MI that infection prevention and control (IPC) resources in community settings were “very, very limited” and each Community Healthcare Organisation “needs to have its own capacity”.

According to HPSC data covering the acute sector, there were 15 new CPE outbreaks in hospitals in 2017, compared with five in 2016, as notified to Departments of Public Health.

There were 40 patients in acute hospitals newly confirmed with CPE in June, compared with 31 in May (there were 433 patients for 2017 versus 282 in 2016).  One invasive CPE infection was notified in June and one in May.

Significant outbreak

On 9 August 2018 there was a reminder that CPE continues to threaten patient safety, with the University of Limerick (UL) Hospitals Group confirming it was managing a significant outbreak and that “strict” visitor restrictions were in place.

As of 15 August, there had been 21 new CPE detections associated with this outbreak since early June, a UL Hospitals Group spokesperson told MI. All of these cases were colonisations rather than infections and the most recent case was detected on 3 August.

“There are currently four CPE-positive inpatients in UHL [University Hospital Limerick], not all of whom are associated with the current outbreak,” said the spokesperson.

“CPE is endemic in the mid-west and the hospital inpatient population reflects this. New CPE cases are frequently picked up through screening. In addition, patients previously identified as CPE-positive may be readmitted. There have been six outbreaks in UHL since August 2017, of which the current is the most significant. The number of outbreaks in UHL to date in 2018 is four.”

A shortage of isolation facilities is a problem encountered by many acute hospitals, particularly in older buildings such as the main ward block at UHL, according to the Group’s spokesperson. “The long-term solution for this is single occupancy rooms for inpatients such as that provided at the 50-bedded block in Ennis Hospital. UL Hospitals Group plans to provide a new 96-bedded block at UHL and this priority capital project has been included in Project Ireland 2040. An interim solution to provide 60 beds has recently been the subject of a planning application to Limerick City and County Council.”

MI also understands that the UL Hospitals Group will imminently publish a report on CPE-related deaths.

In August 2017, HIQA’s Head of Healthcare Regulation Mr Sean Egan wrote to the HSE’s Director of Acute Operations Mr Liam Woods to inform him that its monitoring activity had “very recently identified that heretofore potentially unrecognised cases of patient mortality may have occurred at the University of Limerick Hospital” as a consequence of CPE infection.

According to UL Hospitals Group, this correspondence related to the external review into the cases of 72 CPE-positive patients who at one point had been cared for at UL Hospitals Group and who subsequently died. “This review was undertaken following a protected disclosure made to the Limerick City Coroner. The review is complete and will be published in the coming weeks. UL Hospitals Group is currently in the process of communicating review findings to the families/next-of-kin of the patients concerned and the review will be published once this process is complete.”

Information on CPE-related mortality at UL Hospitals Group covering the period January 2009 to May 2017 will be published in the review.

Previously, UHL publicly stated there had been three cases of mortality attributed to CPE. A spokesperson for HIQA commented: “The hospital has since conducted a further analysis with independent external input which revises this figure. As the hospital are in the process of openly disclosing the findings from this analysis to relatives of the deceased, it would not be appropriate for HIQA to comment further on this matter at this time.”

The Authority’s spokesperson also noted that UHL “is in compliance” with national screening guidelines on CPE.

The HSE, meanwhile, is not undertaking work to assess the number of CPE-related deaths nationally. “CPE-related infection usually occurs in people who already have complex underlying illness, for example cancer or major surgery,” says a spokesperson. “When patients with such complex illness die it is often very difficult to assess how much any one factor contributed to the patient’s death at that particular time.  Making that assessment is a matter of clinical judgement. It requires a detailed study of the patients’ records usually conducted independently by two or more clinicians.

“This process is very labour intensive and is not practical to do on an ongoing basis. This kind of assessment is performed in research settings and is also very valuable in certain other specific settings such as the recent review in UHL. There is no plan to do this on a routine basis.”

Screening

Screening is critical to management of CPE as it helps contain spread and also quantifies the extent of the problem. But implementation of national screening guidance has fallen short in many cases.

According to the HPSC’s June 2018 report for the NPHET, there is “considerable variation” in screening activity between each Hospital Group, “which suggests variable local implementation of national CPE screening guidance”.

Regarding CPE screens and detections, data was returned by 91 per cent of hospitals for June, with 11,093 screens performed (May saw 100 per cent returns and 13,416 screens). According to a table in the monthly report, the number of screens per month has stayed relatively static since November 2017 (eg, 11,280 in November 2017; 10,518 in February 2018).

On 28 March 2018, Mr Egan wrote to Mr Woods about the lack of compliance with national screening guidelines for CPE “in most acute hospitals inspected by HIQA so far in 2018”.

He wrote that HIQA had inspected seven hospitals against the National Standards for the prevention and control of healthcare-associated infection in acute healthcare settings. Five of these hospitals were found not to be screening all required patients for CPE as expected by the national guidelines. These were Midland Regional Hospital, Tullamore; Cappagh National Orthopaedic Hospital, Dublin; St Vincent’s University Hospital, Dublin; South Infirmary Victoria University Hospital, Cork; and St James’s Hospital, Dublin.

“In these five hospitals we routinely found that there was an awareness that the hospital was not screening all patients as required by national guidelines, and many cited a lack of necessary resources to ensure full compliance with national screening guidelines as a reason for this. Moreover, in some instances, we found that the implementation of these guidelines on the ground was confused or incomplete, meaning that in practice some patients who should have been screened were not — despite an intention by the hospital that they would be screened.

“In contrast, we found that both Portiuncula University Hospital and the Royal Victoria Eye and Ear Hospital were screening all patients in compliance with guidelines – a demonstration that such guidance is implementable.”

In a letter of response on 17 April, Mr Woods wrote that “significant efforts” had been made by the HSE to improve screening for prevention and control of CPE in acute hospitals over the previous six months.

He said he had been “assured” that a minimum level of CPE screening for high-risk patient cohorts was currently in place in all acute hospitals. However, he added, in order to achieve full compliance with the screening guidelines and management of patients with CPE-positive swabs/samples, there were “several key success factors”, some of which were “resource-dependent”.

Mr Woods wrote that “challenges” in implementing adequate CPE screening across all hospitals due to “resource constraints” were identified in 2017.

“A detailed assessment of additional laboratory, administrative and non-pay resources required to provide adequate CPE screening tests in acute hospitals has been completed by the National Response Team and acute hospital services and forms the basis for a business case which is currently under consideration by the HSE Leadership Team. A second business case based on assessment of required infection prevention and control teams to support improvements in management of infection and control of antimicrobial use, has also been completed. A minor capital proposal to support infrastructural projects which will facilitate improvement in infection control in acute hospitals is also in development.”

He stated that while there were multiple factors contributing to variation in implementation of screening in acute services, hospitals and Hospital Groups had “clearly indicated that they need additional targeted resources to achieve sustainable compliance with the requirements for CPE screening”.

Mr Woods added: “It is intended that the increase in available information on CPE infections, screening levels and application of screening guidelines supported by a comprehensive repository of associated policies and plans will provide details on the measures intended to achieve optimum CPE screening levels in all acute services, but will require appropriate financial support from the Department of Health in the context of the service planning and estimates process for 2019.”

So far in 2018, HIQA has conducted 16 inspections in hospitals against the National Standards.

“These inspections have found a need for improvement in most hospitals in the implementation of the HSE’s own CPE screening guidelines – a key control measure in dealing with this issue. In each instance we have escalated this matter within the HSE,” according to HIQA’s spokesperson.

“We are also about to very shortly commence a supplementary programme of inspection against these standards through examining the approach hospitals have in place to ensure proper decontamination of reusable medical devices.

“This programme of supplementary monitoring is important as poor cleaning practices related to reusable medical devices in hospitals internationally have resulted in outbreaks of superbugs such as CPE, for example in California in 2015 – https://www.cdc.gov/hai/outbreaks/cdcstatement-la-cre.html.”

Society warned of ‘crisis’ in clinical microbiology

The specialty of clinical microbiology “is in crisis and severely under-resourced in a number of key areas”, warned a submission from the Irish Society of Clinical Microbiologists (ISCM) to the Health Service Capacity Review consultation process.

The document, which was submitted to the Department of Health in August 2017, was released to the Medical Independent (MI) following a Freedom of Information request.

According to the Society, effective prevention and control of infection, antimicrobial stewardship, diagnostic stewardship and infection management “can only be achieved through having the appropriate multi-disciplinary teams in place in all healthcare settings (including joint appointments across hospital and non-acute hospital settings, to address the critical lack of such resources outside of acute hospitals)”.

These teams comprise medical microbiologists, infectious disease specialists, infection prevention and control nurses, antimicrobial pharmacists, surveillance scientists, and dedicated administrative and ICT support.

While the Society welcomed actions such as the establishment of a dedicated HSE response team on CPE/HCAI and completion of a national action plan on AMR, its submission pointed to a number of substantial infrastructural deficits. For example, the requirement for increased laboratory capacity for multi-drug resistant organism surveillance, utilising high throughput molecular technology, was “urgently required” at both regional and national level. Physical infrastructure and ICT were other prominent issues raised in the document.

The list of resources required to deliver “clean, safe care” may appear “daunting”, it noted, but there was ample evidence that investment in these areas was cost-effective, reduced avoidable illness and death and improved patient flow.

The submission referred to morbidity and mortality risks associated with HCAI patients with infection caused by resistant bacteria had a two- to three-fold increased risk of dying as a result of their infection, compared to infections caused by non-resistant bacteria. There was no accurate data on the number of HCAI- or AMR-related deaths in Ireland, but extrapolating from international data, it was likely that at least 1,000 people in Ireland per year die as a direct result of HCAI or antibiotic resistant infection. The Society noted this figure is higher than deaths related to breast cancer and road traffic accidents combined.

Ireland was facing a number of critical risks from increasing antimicrobial resistance, according to the submission. It said bacteria carried in the large bowel, such as E.coli, Klebsiella, and Enterococcus, are a frequent cause of HCAI in Ireland and are becoming increasingly resistant to antibiotics.

The rising resistance among these bacteria “is driven by antibiotic use, particularly in nursing homes and hospitals”. The spread of these bacteria from person to person is linked to overcrowding, understaffing, poor hospital infrastructure, failure to apply infection control precautions, and contamination of medical equipment and the environment by faeces.

Examples of critical issues included CPE, but also a national outbreak of multidrug-resistant Klebsiella pneumoniae (MDRKP), ongoing since 2013, with 914 cases of MDRKP colonisation or infection reported across the country between 2014 and 2015. “Most of these have occurred among inpatients in hospitals, but a significant proportion are occurring among nursing home residents and people in the community,” outlines the submission.

Furthermore, Ireland had the highest proportion of vancomycin-resistant enterococci (VRE) bloodstream infection in Europe (45.6 per cent in 2015). Recent data showed that about one-in-five patients with VRE bloodstream in Irish hospitals died as a result of their infection, outlined the submission. In 2014, some 31 per cent of VRE bloodstream infections in Ireland were related to invasive medical devices, such as intravenous lines.

The submission acknowledged that the rate of bloodstream infections caused by methicillin-resistant Staphylococcus aureus (MRSA) had declined in recent years. However, Ireland still had one of the highest rates in Europe and MRSA remained a common cause of other types of HCAI in Ireland (such as surgical site infections).

Additionally, high levels of antibiotic use in the community was leading to increasing resistance among E.coli (a frequent cause of kidney infections and bloodstream infections) and Streptococcus pneumoniae (the commonest bacterial cause of pneumonia and meningitis).

Dr Eleanor McNamara, President of the ISCM, told MI that the HSE’s CPE/HCAI Response Team has undertaken “tremendous work” in terms of putting in place further guidance and targets. She said that reversing a biological trend, and getting systems embedded to prevent CPE and HCAI, “is going to take a length of time”. She said the extent of CPE monitoring varies across facilities and while there may be many reasons for this, it is primarily due to resources.

She referred, for example, to laboratory capacity and equipment, noting numerous advantages of molecular screening over a culture-based technique. She said there needs to be national capacity for molecular CPE screening, such that it can be accessed by facilities on a city or regional basis.

In response to a question from MI, Dr McNamara confirmed that the issue of new-entrant consultant salaries is also affecting the specialty of clinical microbiology. “Without a doubt, the new-entrant salary is an absolutely huge problem… it is affecting all consultant posts in every specialty.”

However, Dr McNamara noted as positive that three new consultant microbiology posts had recently been advertised, in addition to three replacement posts.

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