Reducing the incidence of healthcare associated infections (HCAIs)
Despite the best efforts of hospital infection control teams, infections acquired whilst in hospital remain a significant source of morbidity and mortality among patients. They also place a considerable burden on the wider health system, prolonging hospital stays, increasing the cost of treating patients and requiring costly interventions such as placing patients in side rooms to prevent onward transmission of their infections. Finding more sensitive and specific ways of detecting and investigating outbreaks of these infections - which are often resistant to many frontline antibiotics - and preventing their spread, is crucial.
How genomics will improve outbreak investigations
Microbiological investigation of potential outbreaks typically relies on ‘typing’ - where a small portion of the genome of each isolate of bacteria collected from a patient or environmental site is sequenced to determine the degree of similarity or difference between each bacterial sample. Highly similar samples indicate that patients have become infected from a common source - whether human or environmental. Such typing methods are however limited in their resolution and are often unusable for distinguishing between bacterial samples. The infection control team is left with no clear picture of whether there really is an outbreak and, if there is, where it started and how it is spread.
Whole genome sequencing (WGS) of bacterial samples can overcome the limitations of existing molecular typing methods. WGS effectively measures every one of the millions of DNA bases in a bacterial genome, therefore differentiating between bacterial samples that would appear identical with current typing methods. Indeed, there are now many published examples of how this higher resolution WGS based analysis can be used to resolve the sources and transmission chains of outbreaks.
The next step in moving pathogen WGS from the research laboratory to the frontline healthcare is to understand how these technologies perform in the real world. This is an exciting new technology for which health services must prepare - hospital infection control services need to know when and how to use it, how to interpret the results it provides, and most importantly whether the appropriate use of these results will lead to improvements in patient outcomes and / or improve the cost-effectiveness of hospital infection control.
Pathogens, plumbing and genomics: tracking the sources of infection in a hospital burns unit
An important new study published in BMJ Open this week begins to tackle some of these questions by deploying WGS based outbreak investigation in a prospective observational surveillance study of a newly opened hospital burns unit. Burns patients are particularly susceptible to becoming infected with Pseudomonas aeruginosa, an opportunistic pathogen commonly associated with water sources. As hydrotherapy is a mainstay of burns treatments, good management of the cleanliness of the water supply and plumbing is essential to minimise the risk of infection through this route. In this study patients and their environment were screened regularly for P. aeruginosa. If they became infected samples from both patient and the environment (including from the water system) were analysed by WGS to attempt to determine the source of the infection.
During the study period five patients became infected with P. aeruginosa.Using WGS, in combination with careful epidemiology, the team were able to determine unambiguously that the hydrotherapy showers were the source of the infection in three of these cases, and even to identify which specific plumbing components in the water supply were colonised with P. aeruginosa. This information drove the ward team to instigate a whole series of enhanced infection control measures, including additional cleaning of the showers and the ward environment. It also provided important impetus to the ongoing implementation of Department of Health guidelines on the management and surveillance of the water supply, and ultimately the installation of new filtered water systems in the highest risk water outlets on the ward. Although a causal link to these interventions cannot be made, it is notable that following these changes in practice, no further patients became infected during the final six months of the study.
From pilot study to frontline service - what will it take?
This paper provides an excellent demonstration of how a WGS informed surveillance programme can support real improvements in infection control when used prospectively in a frontline hospital setting. It also highlights several questions that remain to be addressed prior to implementation of this technology across the health service. Among the most pressing are:
- How and when should we use genomics? – Should hospitals be instituting prospective genomic surveillance for key infections, or should genomics be used reactively to respond to suspected outbreaks? Should it be used across the healthcare system, or only where patients are at highest risk of HCAIs? Answers will depend on cost of sequencing and analysis, the underlying epidemiology of the infections being managed, the configuration of any existing outbreak detection or investigation pathways, and the infection control systems in place to respond to any outbreak detected.
- Will the use of genomics in managing infectious disease prove cost effective for the health system? – This study, and others, has demonstrated that the use of genomics can significantly focus and rationalise infection control measures undertaken in response to a putative outbreak. What is less clear is whether improving the sensitivity and specificity of outbreak detection and investigation will lead to a net increase or decrease in infection control costs for a healthcare setting, and whether the existing infection control systems within those settings will be sufficiently well optimised to realise the benefits of enhanced genomic services.
Despite these words of caution, we remain optimistic that using genomics to improve the quality of infection control practice in healthcare and community settings is likely to have a significantly positive impact on patients and populations in the next few years. The health system must, however, urgently address the questions highlighted above, particularly around establishing evidence of cost-effectiveness, to ensure that insights provided by studies such as this are translated as effectively and rapidly as possible into frontline practice.