While rates of healthcare-acquired infection are falling, thanks to ward cleaning campaigns and improved screening, microbiologists believe targeted screening using a new wave of devices is a vital new weapon in the war against bacteria
Methicillin-resistant Staphylococcus aureus (MRSA) has been the scourge of modern hospital and health systems. Its escalation has been blamed on a number of areas – poor hygiene, lack of consistent cleaning and an overdependence on antibiotics. In addition, community-associated MRSA (CA-MRSA) has spread in the past few years, feeding the pipeline of infection in hospitals, and underscoring the need for comprehensive infection control programmes as patients and visitors ‘import’ the superbug into a hospital setting from the community.
S. aureus is responsible for many serious infections and is one of the most frequently isolated bacteria from patients with healthcare-associated infections (HAI). It is believed that four million HAIs and 37,000 deaths are attributable to these infections each year in the EU, with up to 10% of patients in an EU hospital setting getting a HAI at some stage. The burden placed on healthcare settings is enormous, with growing resources having to be directed at combating infections like MRSA.
As early as 2004, the National Audit Office in the UK estimated that infections such as MRSA killed 5,000 people each year in the UK and hospital-associated infections cost the National Health Service around £1bn a year. However, the last few years have seen a blitz on MRSA and other healthcare-acquired infections such as Clostridium difficile.
There has often been disagreement over the best way to tackle outbreaks, as episodes of deep cleaning, screening of patients and efforts to reduce use of drugs have all had an impact on MRSA.
In the UK, figures show that cases have fallen in the last few years, driven in part by government-set targets on infection control.
Figures for April-June 2009, for example, showed 509 cases of MRSA, compared with 839 in the same period in 2008. That is down from the high of almost 2,000 cases for a similar period in 2004. Vigilance and the fight against MRSA have to continue.
The most effective way to combat MRSA is still the subject of debate. A range of strategies have been advocated by national professional bodies and health agencies to try to contain the transmission of MRSA in healthcare facilities and the wider community – these include improvements in basic hygiene and hand-washing in health units. There are also control measures based on screening of individuals, but there is a lack of consensus about whether this should be targeted at high-risk groups on admission to hospital or conducted universally.
A 2008 study published in the Annals of Internal Medicine looked at the effect of large-scale expanded surveillance for methicillin-resistant Staphylococcus aureus on healthcare-associated MRSA.
Focusing on a three-hospital, 850-bed organisation with about 40,000 annual admissions, the study concluded that the introduction of universal admission surveillance for MRSA was associated with a large reduction in MRSA disease during admission and 30 days after discharge.
However, microbiologist Dr Michael Millar, who is involved in the screening programme at the Barts and The London NHS Trust, has questioned the wisdom of screening all hospital patients for MRSA in England amid fears that the tests produced too many false results. All hospitals in England have had to screen patients being admitted for non-emergency surgery since April 2009 and, by next year, must ensure all emergency cases are tested.
However, many other countries – including the US, the rest of the UK and much of mainland Europe – screen only the most at-risk patients, such as those who have been in and out of hospital in recent months. Dr Millar said that was a much more sensible policy and should be re-instated in England.
“The problem with screening everyone is that in low-risk groups you get as many false positives as positives, if not more,” he said.
Improved cleaning regimes have also been advocated. Consultant microbiologist Dr Stephanie Dancer, from NHS Lanarkshire in Scotland, led a study which sought to provide evidence to support the value of cleaning in hospitals and of measuring those standards. Her study concluded that the introduction of extra cleaners on wards had a measurable effect on the clinical environment and reduced levels of microbial contamination at hand-touch sites.
The fight against MRSA has also been stepped up with technological aids and devices. Last year, Roche introduced a new device it says will help improve the detection, prevention and control in healthcare settings. The LightCycler MRSA Advanced Test is a qualitative in vitro diagnostic test for the direct detection of nasal colonisation with MRSA. Daniel O’Day, head of Roche Molecular Diagnostics, said: “As more guidelines recommend or require aggressive screening, it is important that healthcare professionals have access to fast, reliable products that can help improve medical outcomes. This new test will aid infection control programmes, and ultimately result in better patient care.”
Roche’s LightCycler 2.0 instrument uses nasal swab specimens from patients suspected of colonisation, using the company’s patented real-time polymerase chain reaction (PCR) technology. A ready-to-use format helps to ensure safety and aid productivity in the lab, and the instrument can handle flexible batch sizes and flexible throughput.
This is the first system to introduce hybridisation probes, true melting curve analysis, automated absolute quantification, and relative quantification with efficiency correction.
Dr Kathryn Stowell is associate professor in biochemistry in the Institute of Molecular BioSciences at Massey University, Palmerston North, New Zealand. She said in vitro detection of MRSA colonisation was critical in helping to better understand and combat the infection in a healthcare setting. “Forewarned is forearmed,” she said. “If entry points can be determined, it is easier to prevent and treat, given the limited range of antibiotics that are effective.”
More recently, Dr Stowell has been using Roche’s LightCycler 480 System for RT-qPCR to study gene expression responses to a number of different environmental cues and to quantify chromatin immunoprecipitation (ChIP) assays to study chromatin modifications in patient melanomas.
She said: “We also use HRM (high-resolution melting) for genotyping SNPs (single nucleotide polymorphisms) to study familial relationships. We have also used HRM and, in some instances, Hyb probe assays for SNP discovery in the search for causative mutations.” She believes it also has a role in the fight against MRSA and other infections. “The 480 system could be used to detect trace amounts of any infectious organism as long as we have access to the appropriate discriminatory DNA sequences that can be used to design probes,” she said.
Dr Stowell said one of the advantages of Roche’s LightCycler systems is that it is versatile and very little material is required.
“Assays are relatively easy to set up and inexpensive if something like HRM is used,” she said. “Not all sequences lend themselves to HRM, but there are other chemistries that could be used.”
In a 2009 paper looking at laboratory tools and strategies for MRSA screening, surveillance and typing, Professor Mark Struelens and his co-authors acknowledge the public health burden and the levels of alarm caused by MRSA: “Effective MRSA risk management in the healthcare system as well as in the community should rely on accurate detection of reservoirs and sources of transmission, as well as on close monitoring of the impact of interventions on disease incidence and bacterial dissemination.
“MRSA carrier screening and disease surveillance, coupled with molecular typing, are key information tools for integrated MRSA control and individual risk assessment.
“These tools should be tailored to the distinct needs of local interventions and national prevention programmes.”
The paper concludes that MRSA carrier screening, surveillance and molecular typing are pivotal information tools for integrated MRSA control programmes and that new technologies offer great potential for “more effective and timely interventions”.
“There is an urgent need for health professionals, in vitro diagnostic companies and policy-makers to work together to assess the cost-effectiveness of these tools for safer care of patients and protection of the public against the tide of MRSA,” they state.
Hospitals are fighting back. Armed with cleaning strategies, a realigned approach to antibiotic use, screening and new devices and techniques, they are gaining ground in the battle against MRSA.
1. Robicsek A et al. Ann Intern Med 2008;148:409-18.
2. Dancer SJ. The role of environmental cleaning in the control of hospital-acquired infection. J Hosp Infect (2009), doi: 10.1016/j.jhin.2009.03.030
3. Struelens MJ et al. Clin Microbiol Infect 2009;15:112-9.