Q J Med 1997; 90:243246

Mini-review QJM
Is control of methicillin-resistant Staphylococcus aureus justified?
I .C .J . BOWL ER From the Public Health Laboratory Service, John Radcliffe Hospital, Oxford, UK

The impact of staphylococcal disease

Staphylococcus aureus is a normal commensal of the human skin carried by up to 40% of the population in the apocrine-gland-rich areas of the nose, perineum and axillae. Carriage is more common in patients with diabetes, chronic renal failure, psoriasis, eczema and HIV.1 It is also an important pathogen in both the home and the hospital. In the community, it is the commonest cause of skin sepsis and its rarer sequelae, acute septic arthritis, osteomyelitis and endocarditis.2 It is occasionally responsible for acute otitis media and sinusitis, but rarely causes pneumonia except following influenza.3 The mortality of community-acquired Staphylococcus aureus bacteraemia, which is often associated with occult endocarditis, is in the order of 20%.4,5 In hospitals, despite the advent of numerous preventative strategies, Staphylococcus aureus is responsible for about 20% of all hospital-acquired infection.6 It causes the majority of wound infections following clean surgical procedures, and is the most important cause of peripheral and central intravascular-access-device-associated infection.7,8 Staphylococcus aureus bacteraemia due to a removable source, such as an intravascular device, carries a complication rate (seeding onto heart valves, into bones and/or joints) of the order of 5%, even after aggressive anti-staphylococcal therapy for two weeks.9 staphylococcal disease. The most important are blactams such as flucloxacillin, and first- and secondgeneration cephalosporins. In general practice, the macrolides such as erythromycin are also used extensively. In hospital, antibiotics usually comprise 2030% of the total drug budget. The bulk of antistaphylococcal antibiotic use is intravenous, in the form of prophylaxis for surgical procedures.26 The spread of methicillin-resistant S. aureus (MRSA) threatens the efficacy and convenience of current oral anti-staphylococcal therapy in general practice and, by forcing changes to surgical prophylactic regimens, will send hospital drug costs spiralling. MRSA carry the Mec gene, coding for a new penicillin-binding protein (PBP2a) which renders the organism insusceptible to all b-lactams, monobactams such as aztreonam, and the newer carbapenems, imipenem and meropenem.10 Most strains carry other resistance determinants rendering them insusceptible to the macrolides and quinolones. Susceptibility to tetracycline and the aminoglycosides (gentamicin and netilmicin) is variable. Most strains are susceptible to rifampicin and fusidic acid and all are sensitive to the glycopeptides, vancomycin and teicoplanin.11 The oral therapy of MRSA infection is therefore limited to expensive antibiotics which are poorly tolerated, particularly by the elderly, which are subject to a number of well-known drug interactions, and to which S. aureus readily mutates to resistance. In hospital, invasive disease can only reliably be treated with glycopeptides which are very costly, must be given intravenously, are associated with renal toxicity, and which therefore require expensive

The clinical significance of methicillin resistance

Fortunately, there are a wide range of simple and cheap antibiotics available for the treatment of

Address correspondence to Dr I.C.J. Bowler, Public Health Laboratory Service, John Radcliffe Hospital, Oxford OX3 9DU Oxford University Press 1997

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monitoring.14,15 It is clear that without control policies, MRSA become endemic in acute hospitals, responsible for at least half of the staphylococcal disease burden.16 If adequate prophylaxis for staphylococcal sepsis in this environment is to be given to surgical patients undergoing operations where S. aureus is an important cause of post operative sepsis, then a glycopeptide must be included in the regimen. This would add approximately 600 000 to the drug budget of the average acute hospital in the UK.17 It is the preservation of our current antistaphylococcal armamentarium, and the cost and inconvenience of the alternatives, which is the driving force behind MRSA control strategies. Control cannot be justified in terms of virulence, since the mortality and morbidity of MRSA infections, if appropriately treated, are no different from those caused by methicillin-susceptible strains.12 The attack rate depends on the susceptibility of the population in which the organism is spreading. Spread on a cardiothoracic unit is likely to result in major mortality and morbidity, particularly if inappropriate antibiotics are used for surgical prophylaxis. In the care of the elderly ward, most patients will usually be harmlessly colonized.13

by MRSA has increased from 25 in 1993 to more than 100 by 1996.25 The reasons for this are numerous. Hospitals are now run at near-full bed occupancy. A single admission often entails stays on several wards to maximize bed usage. This ensures that patients carrying multi-resistant organisms have many patient and staff contacts in a short period. The co-ordination of the use of ITU beds means that patients move rapidly between care settings where the prevalence of multi-resistant organisms and antibiotic usage is greatest. There may be management resistance to infection-control measures such as the closure of wards, which because of high bed occupancy, often means the cancellation of elective surgery, which impacts on waiting-list targets. Shortages of permanent nursing staff, and reliance on bank nursing mitigates against the consistent application of MRSA risk-management policies, which rely heavily on good knowledge of procedures amongst the nursing staff. Other factors which may be at play are the increase in age, and therefore susceptibility, of the in-patient hospital population, and the increasing use of antibiotics both in the community and the hospital.26

Control measures Epidemiology

The spread of MRSA in hospital is predominantly from patient to patient on the hands of staff. Handwashing therefore is an important part of any control strategy. The organism is also shed into the environment on the skin scales of colonized or infected patients. Therefore single-room isolation is also important in control.18,19 Occasionally staff members become nasal carriers and can pass the organism on to patients, but this seems to be unusual.20 Risk factors for the acquisition of MRSA by patients are duration of stay, presence of wounds/ ulcers and invasive devices and prior antibiotic therapy.21 The organism spreads rapidly in the intensive care and surgical setting. Outbreaks are less common on medical wards, though once established, particularly in the care of the elderly setting, it may be difficult to eradicate.22 The few data available on transmission characteristics in residential and nursing homes suggest that spread of the organism in these care settings is unusual. Spread of MRSA in the home is uncommon, and even if family members do become colonized, there is no evidence that such acquisition is associated with an increased attack rate for staphylococcal disease.23,24 Therefore there is no rationale for special control measures in the home. Despite the application of control measures in the acute sector, the number of hospitals affected Control measures should be tailored to the epidemiological milieu in which the organism is found, and must be shown to be cost effective. In hospitals with a low prevalence of MRSA where b-lactams are the mainstay of antibiotic therapy and prophylaxis, aggressive control measures are justified.18 Patients known to be colonized or infected are nursed so as to minimize the risk of spread to other patients. If a new case of MRSA colonization is discovered, other patients on the ward are swabbed to establish whether transmission has taken place, and any new cases discovered are also isolated. Unfortunately, the results of MRSA swabbing are not usually available for 3 days, during which time further spread may occur. Patients found to be colonized need to be carefully counselled about the need for single-room isolation, and reassured that the presence of the organism does not indicate that infection is more likely, or that their treatment will be compromised.
Table 1 Precautions for MRSA-colonized in-patients

Single room isolation with commode or own toilet Plastic aprons to be worn by staff for examination and nursing procedures Gloves to be worn by staff when handling skin lesions Linen to be treated as infected Strict hand washing and disinfection of stethoscopes after examining patient

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Each patient should be assessed for their suitability for decolonization. Patients with intact skin colonized with mupirocin-sensitive strains who will be in-patients for more than a week are most suitable. If spread of the organism continues, then other measures, such as cohort nursing, with physical separation of new admissions from those already on the ward who have been exposed to MRSA, should be attempted. Should this fail, ward closure may be required. In hospitals where the organism is endemic, these expensive control measures are not justified.18 Modelling of outbreaks and studies of the costeffectiveness of MRSA control measures are areas of urgent research priority. Guidelines for the control of MRSA in the community, including nursing and residential homes, have recently been published.23 There is an emphasis on prevention of spread of all infections by appropriate good general hygiene standards.
Table 2 Precautions for MRSA-colonized patients in residential and nursing homes They should be encouraged to have a normal life without restriction or the need to be isolated They may share a room so long as neither they nor the person with whom they are sharing has open sores or wounds, drips or catheters They may join other residents in communal areas so long as any sores or wounds are covered They may receive visitors and go out of the home Staff should carry out any clinical procedures and dressings in the residents own room

be made on the application of resources to control programmes.

References
1. Wenzel RP, Perl TM. The significance of nasal carriage of Staphylococcus aureus and the incidence of post-operative wound infection. J Hosp Infect 1995; 31:1324. 2. Eykyn S. Staphylococcal sepsis. The changing pattern of disease and therapy. Lancet 1988; i:1004. 3. British Thoracic Society and Public Health Laboratory Service. Community-acquired pneumonia in adults in British hospitals in 19821983: a survey of aetiology, mortality, prognosic factors and outcome. Q J Med 1987; 62:195220. 4. Nolan CM, Beaty HN. Staphylococcus aureus bacteraemia. Am J Med 1976; 60:495500. 5. Cunney RJ, McNamara EB, Al Ansari N, Smyth EG. Community and hospital acquired Staphylococcus aureus septicaemia: 115 cases from a Dublin teaching hospital. J Infect 1996; 33:1113. 6. Meers PD, Ayliffe GAJ, Emmerson AM, Leigh DA, MayonWhite RT, Mackintosh GA, Stronge JL. Report on the national survey of infection in hospitals 1980. J Hosp Infect 1981; 2:Supplement 151. 7. Strachan CJL. Antibiotic prophylaxis in peripheral vascular and orthopaedic prosthetic surgery. J Antimicrob Chemother 1993; 31:Supplement B 6578. 8. Elliott TSJ. Line-associated bacteraemias. Comm Dis Rep 1993; 3:R916. 9. Jernigan JA, Farr BM. Short-course therapy of catheterrelated Staphylococcus aureus bacteraemia: a metaanalysis. Ann Intern Med 1993; 119:30411. 10. Chambers HF, Sachdeva M, Kennedy S. Binding affinity for penicillin binding protein 2a correlates with in vivo activity of b-lactam antibiotics against methicillin-resistant Staphylococcus aureus. J Infect Dis 1990; 162:70510. 11. Methicillin-resistant Staphylococcus aureus in England and Wales. Comm Dis Rep 1992; 2:R259. 12. Peacock JE, Moorman DR, Wenzel RP, Mandell GL. Methicillin-resistant Staphylococcus aureus: microbiological characteristics, susceptibilities, and assessment of virulence of an epidemic strain. J Infect Dis. 1981; 144:57582. 13. Cox RA, Conquest C, Mallagan C, Marples RR. A major outbreak of methicillin-resistant Staphylococcus aureus caused by a new phage-type (EMRSA-16). J Hosp Infect 1995; 29:87106. 14. Keane CT, Cafferkey MT. Re-emergence of methicillinresistant Staphylococcus aureus causing severe infections. J Hosp Infect 1984; 9:616. 15. Saunders NJ. Why monitor peak vancomycin concentrations? Lancet 1994; i:174850. 16. Meers PD, Leong KY. The impact of methicillin and aminoglycoside-resistant Staphylococcus aureus on the pattern of hospital-acquired infection in an acute hospital. J Hosp Infect 1990; 16:2319. 17. Personal Communication. J. Dorey, Chief Pharmacist, Oxford Radcliffe Hospital Trust, Oxford. 18. Revised guidelines for the control of epidemic methicillinresistant Staphylococcus aureus. Working Party Report. J Hosp Infect 1990; 16:35177. 19. Mulligan ME, Murray-Leisure KA, Ribner BS, Standiford HC, John JF, Korvick JA, Kauffman CA, Yu VL. Methicillin-

In the patients own home, the family need take no special precautions. However, those coming into the home to provide care such as care assistants, district nurses and the general practitioner, should wear an apron when performing intimate nursing care, and gloves when handling skin lesions, followed by careful hand washing.

Conclusion
Despite the application of control measures in acute hospitals, MRSA continues to spread, because it is becoming endemic in care settings where the application of aggressive control measures is not feasible. There is an urgent need to establish the dynamics of MRSA transmission in the community, since it is the spread in this setting which is a threat to control in the acute-care sector. Such research also needs to establish the cost-effectiveness of aggressive control measures in the acute sector in the face of constant reintroduction of the organism from the community, so that rational decisions can

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23. Guidelines on the control of methicillin-resistant Staphylococcus aureus in the community. Working Party Report. J Hosp Infect 1995; 31:112. 24. Frenay HME, Vandenbroucke-Grauls CMJE, Molkenboer MJCH, Verhoef J. Long term carriage, and transmission of methicillin-resistant Staphylococcus aureus after discharge from hospital. J Hosp Infect 1992; 22:20715. 25. Epidemic methicillin resistant Staphylococcus aureus. Comm Dis Rep 1996; 6:197. 26. Emmerson AM, Enstone JE, Griffin M, Kelsley MC, Smyth ETM. The second national prevalence survey of infection in hospitalsan overview of results. J Hosp Infect 1996; 32:17590.

resistant Staphylococcus aureus: a consensus review of the microbiology, pathogenesis, and epidemiology with implications for prevention and management. Am J Med 1993; 94:31328. 20. Lessing MPA, Jordens JZ, Bowler ICJ. When should health care workers be screened for methicillin-resistant Staphylococcus aureus. J Hosp Infect 1996; 34:20510. 21. Casewell MW. Epidemiology and control of the modern methicillin-resistant Staphylococcus aureus. J Hosp Infect 1996; 7 (Supplement A):111. 22. Coello R, Jimenez J, Garcia M, Arroyo P, Minguez D, Fernandez C, Cruzet F, Gaspar C. Prospective study of infection, colonisation and carriage of methicillin-resistant Staphylococcus aureus in an outbreak affecting 990 patients. Eur J Clin Micro Infect Dis 1994; 13:7481.