To notify, or not to notify – that is the question

Posted on October 23, 2019   by Professor Garry Blakely

In this blog, Professor Garry Blakely, from the University of Edinburgh's School of Biological Sciences, discusses carbapenemase-producing bacteria and the importance of surveillance. In August 2019, Professor Blakely attended a Public Health England (PHE) steering group with a number of clinicians and diagnostic staff to discuss the limitations and effects that reporting infections from carbapenemase-producing bacteria could have on healthcare systems.

The O’Neill report has left a lasting mark on both the public and scientific perceptions of antimicrobial resistance (AMR). The shocking prediction of 10 million deaths globally by 2050 as a result of AMR infections has spurred many governments into action to address this threat to public health and the associated drain on public finances.

Despite high-level political declarations to support policies aimed at tackling AMR, the reality of financial constraints will be the determining factor of success in the fight. The UK Government has recently published its medium and long-term plans to “contain and control” AMR, with an emphasis on surveillance, research, awareness and education.

While each of these components play a crucial role in government plans, we focus on surveillance which allows the epidemiological monitoring of specific infectious agents to predict and hopefully manage spread. From a bacteriological viewpoint, one of the greatest threats to public health in the UK originates from carbapenemase-producing bacteria (CPB), for example, some members of the order Enterobacterales and those in the Pseudomonas and Acinetobacter genera.

Antibiotics in the b-lactam family have been a cornerstone of modern medicine. However, with the increasing resistance of bacteria to many first and second-line drugs, clinicians are having to fall back on b-lactams of ‘last resort’, such as carbapenems. In 2017, the World Health Organisation described the critical need to develop new antibiotics against multi-drug resistant Acinetobacter, Pseudomonas and members of the Enterobacteriaceae, including Klebsiella, Serratia, Proteus and Escherichia coli.

Carbapenem-resistance is caused by genetic elements that can be shared between members of different genera. In one study, Enterobacteriaceae collected from clinical settings in the UK during 2013-2014 had an estimated carbapenem resistance of 36%. This data, combined with the observation that patients with infections caused by carbapenemase-producing Enterobacteriaceae (CPE) have a significantly poorer clinical outcome, illustrates the urgency of the situation.

This emerging threat was identified by Public Health England (PHE) and an enhanced electronic system for reporting carbapenem-resistant Gram-negative bacteria was implemented in 2015. While reporting CPB in acute settings is broadly covered under the The Health and Social Care Act 2008: Code of Practice on the prevention and control of Infections, the reporting of specific bacterial species or their resistance mechanisms is not required as part of the ‘Notification of Infectious Diseases’ under the ‘Health Protection (Notification) Regulations 2010’.

Since CPE in the bloodstream (bacteraemia) has been identified as presenting poor patient outcomes, PHE has sought advice from health care professionals on the requirement for inclusion of defined CPB under the Health Protection Regulations.

A PHE steering group proposed that invasive CPB should fall under the legislation for notifiable diseases and causative organisms. The notification would obviously include identification of the organism, but additionally would require identification of the genetic basis for resistance. In August 2019, a workshop comprised of clinicians and diagnostic staff was convened by PHE to address the effects of such reporting on those practitioners at the coal face. Attendees were tasked with assessing the utility of invasive CPB reporting within four main categories:

1) Microbiological definition

2) Infection control

3) Antimicrobial stewardship

4) Public health actions

A number of immediate questions were raised about the clinical purpose of CPB inclusion and the increased workload and costs of reporting. Key questions included:

• Will notification of a CPB bacteraemia to PHE improve the outcome for the patient?
• Will it alter the normal procedures of infection control teams?

By the time a CPB bacteraemia is identified it will probably be too late for effective infection prevention and control measures. From an infection control perspective, what is ideally needed is a rapid screen for colonisation with CPB on admission. Spread of CPB by unidentified patients is potentially a greater risk to a hospital population than a bacteraemia case. Screening via rectal swabbing is already carried out in many hospitals for specific subgroups of patients. However, screening is time-consuming and costly, so without improved technology there needs to be a pragmatic solution for surveillance. Although far from ideal, part of the solution might be notification of invasive CPB.

It has been widely reported in the media that the NHS is suffering from the increasing burden of patient numbers and decrease in funding. Clinical and diagnostic staff feel overworked and underpaid, which is leading to high staff turnover and a decrease in  morale. The reporting requirements for invasive CPB will also include identification of the genetic basis for resistance, however, currently around 50% of hospitals in England have the necessary equipment for this molecular determination.

All identified strains must also be submitted to PHE for archiving, with the cost of submission being borne by each NHS Trust. It is clear that any requirements must be simple to implement and easily integrated with the current second-generation surveillance system. Will the legal requirement to report these infections be supported by additional funding to buy equipment and cover the extra workload? The answer to this question is far from clear.

While surveillance of nosocomial infections caused by Staphylococcus aureus and Clostridium difficile has proven its worth in reducing the number of cases, it is less clear whether notification of invasive CPB will have the same impact. By the time a CPB bacteraemia is identified in a hospital, the proverbial horse will have already left the stable. One obvious public health benefit would be that onward locations for patients, such as care homes, could be notified that an individual is potentially colonised. However, this does not rely on legislation for notification but should already be covered by the Health and Social Care Act. In an ideal scenario, hospitals would screen all patients quickly and cheaply on admission and appropriate infection control measures would be applied. Unfortunately our imperfect world consists of overworked laboratory staff with dwindling resources and increasing bureaucracy; hardly ideal conditions to fight the evolutionary wildfire of AMR which has been fuelled by our over-use of antibiotics.