BSc MSc PhD
Communicable Disease Surveillance Centre
Health Protection Agency
For a bug more used to a quiet life as a coloniser of some of the least glamorous body sites (about 30% of people at any one time carry the bug in their nose, armpits, throat or perineum), these are giddy times for Staphylococcus aureus. A series of front-page stories in the national press, television documentaries and speeches by leaders of political parties have shot the organism into the A-list of celebrity pathogens in the UK.
The reason is the rise of methicillin-resistant S aureus (MRSA). Though usually no more virulent than the methicillin-sensitive variant MSSA (both types commonly carry an extensive armoury of virulence determinants that enable them to cause life-threatening disease in vulnerable hospitalised patients), MRSA is particularly worrying because of the lack of therapeutic options; methicillin resistance is commonly accompanied by a number of other antibiotic resistance determinants in clones that spread well in hospitals.
MRSA was first detected in the UK in 1961, shortly after the introduction of methicillin.(1) By the late 1960s, increasing numbers of MRSA were reported in many European hospitals.(2,3) For reasons that are not well understood – the changing pattern of antibiotic use is one possibility – MRSA prevalence declined in the 1970s.(4) In the 1980s, new “epidemic” clones emerged and reversed this trend. These lineages appeared to have greater transmissibility than previously encountered MRSA variants, and they could not be controlled by standard infection control measures.(5)
Between 1990–92 and 2000 the proportion of methicillin-resistant cases of S aureus bacteraemia in England increased from 1–2% to about 40%, largely due to two major clones – EMRSA-15 and EMRSA-16.(6,7)
MRSA now accounts for 44% of invasive S aureus isolates in UK hospitals.(8)
Teicoplanin and vancomycin are still the main therapeutic options for serious MRSA infections, and until recently were the only antibiotics for which resistance had not been seen in vivo for S aureus.
Their value has recently been threatened by the emergence and transmission of both glycopeptide intermediate- resistant S aureus (GISA) and fully resistant strains that have acquired the glycopeptide resistance gene from glycopeptide-resistant enterococci.(9,10) Of these, only GISA has been seen in patients in the UK, and it is still rare.(11) Nonetheless, the threat of glycopeptide resistance is still a major concern.
Linezolid, the only commercially available oxazolidinone, is also effective in the treatment of MRSA infections and offers a valuable fall-back option, although resistance in clinical S aureus isolates has already been reported in the UK.(12)
Most patient-to-patient transmission of MRSA is thought to be largely mediated by contact with transiently colonised carers, although other routes, such as airborne spread, are also likely to contribute. Consequently, control efforts in the UK have focused on establishing good hand hygiene among carers and isolating patients colonised or infected with the organism in side rooms, cohorts or isolation units. However, the increasing prevalence of MRSA has necessitated some changes in national control guidelines.
The initial approach recommended a “Search and Destroy” policy, with active screening for MRSA carriage and subsequent patient isolation.(13,14) The much higher MRSA levels seen in the 1990s led to overstretched infection control teams and shortages of isolation facilities. This prompted a revision of the guidelines in 1998; a flexible targeted approach was recommended, depending on the risk to the patient (the type of ward affected), the availability of isolation facilities, and whether or not MRSA was already endemic in the given setting.(15)
It is not clear how effective the measures recommended by these guidelines are. Although the MRSA control literature is extensive, there are serious shortcomings in the quality of the research.(16) Much of the evidence base comes from anecdotal reports or poorly designed studies that are susceptible to many biases.
Analyses of typical “interrupted time series” studies (where interventions are introduced one after the other, interrupting a time series of outcome measures) are almost always inappropriate and likely to lead to incorrect conclusions. Moreover, very few studies have attempted to assess the value of individual control measures. Nonetheless, there is convincing evidence that packages of control measures, including screening, patient isolation, hand hygiene and topical eradication of MRSA carriage, can lead to major reductions in MRSA levels, even in settings where it is endemic.
The high level of endemic MRSA in UK hospitals, the patchy evidence in support of control measures and the large resources required to combat the organism have led some commentators to advocate a laissez-faire policy.(17) Given that MRSA appears to be no more virulent than MSSA, they argue, resources spent attempting to control MRSA would be better diverted elsewhere. If MRSA simply replaced MSSA, this would be a compelling argument. Instead, the available evidence strongly suggests that this is not the case; MRSA appears to have added to the total burden of infection, rather than simply displacing MSSA.(18)
Perhaps the most promising new measure to control MRSA and reduce the incidence of healthcare-associated infections is the National Patient Safety Agency’s “cleanyourhands” campaign. This is a nationwide evidence-based and multifaceted intervention aimed at improving carer hand hygiene throughout the National Health Service’s acute sector. Interventions include the use of promotional materials to improve hand hygiene, measures to encourage patient involvement in the campaign, and the positioning of alcohol-based disinfectant handrubs near to patients.
The level of MRSA as a proportion of S aureus bacteraemias in the UK is currently among the highest in Europe. Among countries participating in the European Antimicrobial Resistance Surveillance System scheme, only Greece has such a high level, although several countries, particularly in Southern and Eastern Europe, have problems on the same scale.(8)
In contrast, in the Netherlands and Denmark, where a rigorous “Search and Destroy” policy is practised, fewer than 1% of hospital S aureus isolates are MRSA. While the “Search and Destroy” policy might be highly effective when prevalence is low, once endemicity has been established the excessive resources required would make such control efforts unfeasible in the UK at present.
If major reductions are to be achieved, interventions that do not become less effective as the size of the problem increases (such as improved hand hygiene and more thoughtful antibiotic use) may have a greater chance of success.(19)
- Jevon MP. BMJ 1961;1:124-5.
- Parker MT, Hewitt JH. Lancet 1970;1:8004.
- Benner EJ, Kayser FH. Lancet 1968;2:741-4.
- Shanson DC. J Hosp Infect 1981;2:11-36.
- Casewell MW. J Hosp Infect 1995; 30 Suppl:465-71.
- Reacher MH, Shah A, Livermore DM, et al. BMJ 2000;320:213-6.
- Anonymous. Commun Dis Rep Wkly 2001;11:7.
- European Antimicrobial Resistance Surveillance System. Available at: www.earss.rivm.nl
- Hiramatsu K, Hanaki H, Ino T, et al. J Antimicrob Chemother 1997;40:135-6.
- CDC. Staphylococcus aureus resistant to vancomycin – United States, 2002. MMWR Morb Mortal Wkly Rep 2002;51:565-67.
- Howe RA, Bowker KE, Walsh TR, et al. Lancet 1998;351:602.
- Wilson P, Andrews JA, Charlesworth R, et al. J Antimicrob Chemother 2003;51:186-8.
- Hospital Infection Society and British Society for Antimicrobial Chemotherapy. Guidelines for the control of epidemic methicillin-resistant Staphylococcus aureus.J Hosp Infect 1986;7:193-201.
- Hospital Infection Society and British Society for Antimicrobial Chemotherapy. Revised guidelines for the control of epidemic methicillin-resistant Staphylococcus aureus. J Hosp Infect 1990;16:351-77.
- British Society for Antimicrobial Chemotherapy, Hospital Infection Society and the Infection Control Nurses Association. Revised guidelines for the control of methicillin-resistant Staphylococcus aureus infection in hospitals. J Hosp Infect 1998;39:253-90.
- Cooper BS, Stone SP, Kibbler CC, et al. BMJ 2004;329:533.
- Barrett SP, Mummery RV, Chattopadhyay B. J Hosp Infect 1998;39:85-93.
- Crowcroft NS, Catchpole M. BMJ 2002;325:1390-1.
- Cooper BS, Medley GF, Stone SP, et al. Proc Natl Acad Sci USA 2004;101:10223-8.
European Antimicrobial Resistance Surveillance System (EARSS)
Hospital Infection Society