Methicillin Resistant Staphylococcus Aureus (MRSA) and its clinical impact
Summary
MRSA is now the most common cause of hospital-acquired infection worldwide and infection rates show no sign of abating. Dr Xavier Emmanuel reviews the evolution of MRSA, its clinical impact and efforts to control and eradicate it.
Key Points
- MRSA is so-called because resistance was described first in relation to methicillin. MRSA is, in fact, resistant to all penicillins and cephalosporines and often to several other unrelated antibiotics.
- Treatment is difficult. MRSA are almost always sensitive to vancomycin and the related teicoplanin. Newer agents are being introduced.
- Rapid spread of MRSA in the 1990s was due to a few closely related MRSA strains known as epidemic or E-MRSA. MRSA is now the most common cause of hospital acquired infection worldwide.
- Antibiotic use, prolonged hospitalisation, serious underlying illness, skin disease, frequent staff-patient contact and the use of invasive devices predispose to invasive MRSA infections.
- General cleanliness, hand-washing and sensible antibiotic use prevent infection. Patient isolation, special nursing procedures and MRSA eradications from staff are needed occasionally.
Declaration of interests: No conflict of interests declared
Staphylococcus aureus (S. aureus) is one of the oldest known and most important of bacterial pathogens, causing a wide range of superficial and deep infections. At the dramatic beginning of the antimicrobial era, it was, like many other pyogenic bacteria, very susceptible to the sulphonamides and later to penicillin. The subsequent story of antibiotic resistance in S. aureus is a good example of the evolving interaction between a pathogenic organism and antibiotics. Clinically important resistance to penicillin was noted soon after its introduction1 and spread rapidly so that, within a decade or so, penicillin resistance in S. aureus was the rule rather than the exception. This resistance is due to the production by the organism of a beta-lactamase enzyme, which lyses the essential beta-lactam ring of penicillin. The 1960s saw the development of a number of semi-synthetic penicillins such as methicillin, nafcillin, and cloxacillin which are more stable to the action of the beta-lactamase. These new agents seemed at first to solve the problem, but their widespread use was again followed by the emergence of resistant strains, described initially in relation to methicillin.2 These strains produce a modified version of a bacterial cell-wall synthesising enzyme, which enables cell-wall synthesis and bacterial multiplication to continue uninhibited even in the presence of the beta-lactamase stable semi-synthetic penicillins. This confers resistance against all antibiotics based on the beta-lactam ring structure, including the cephalosporins, but for historical reasons these strains are known as Methicillin Resistant Staphylococcus Aureus (MRSA). This resistance is also often linked to resistance to several other unrelated groups of antibiotics, so that treatment choices are limited. Typically, MRSA strains are resistant to all the penicillins and cephalosporins, erythromycin and ciprofloxacin. Many strains remain susceptible to gentamicin, cotrimoxazole, tetracyclines, rifampicin and fusidic acid though there are local variations in the distribution of strains. They are almost invariably susceptible to vancomycin and the related compound, teicoplanin, but a few strains have been recently described which show a clinically significant reduction in susceptibility. Newer agents have been recently introduced into clinical use,3 but these are best reserved for situations where there is resistance to the older antibiotics such as vancomycin, or when their use is precluded by adverse effects.
Though recognised as a significant problem by 1971, the spread of MRSA was slow until the late 1980s but accelerated in the 1990s to become a global problem. Genetic analysis has revealed much variation, but a small number of closely related strains, known as epidemic MRSA or E-MRSA strains, account for much of the recent rapid spread through healthcare facilities. Though the magnitude of the problem varies markedly, many areas of the world have seen a dramatic increase in the morbidity and mortality associated with S.aureus infection in recent years. Nearly all of this increase is attributable to methicillin resistant strains. Methicillin resistant S. Aureus is now the single most common cause of serious hospital acquired infections. Bloodstream infections associated with vascular access devices, ventilator associated pneumonias, wound infections in orthopaedics, cardiothoracic surgery, solid organ transplantation and burns, and deep infections like endocarditis and blood-borne osteomyelitis are prominent areas of concern.
Nearly all cases of S. Aureus infections, including MRSA infections, are caused by strains which have previously colonised the patient. In the case of MRSA, this colonisation is very often recently acquired, after hospitalisation, but in some patients, particularly older patients who are resident in care facilities, colonisation may have occurred before admission to hospital.
Methicillin resistant strains do not seem to posses more virulence factors than susceptible strains, but colonisation with MRSA seems more likely to be followed by invasive disease.4 Hospitalised patients frequently receive broad-spectrum antibiotics which eliminate the patient’s healthy commensal bacteria, leaving the field clear for resistant bacteria like MRSA to rapidly establish heavy colonisation. Such heavy colonisation involves the upper respiratory tract and skin, including any surgical wounds or access sites for catheters, and so predisposes to invasive infection. Other factors which increase the likelihood of significant colonisation include prolonged hospitalisation, underlying serious illness, skin diseases such as eczema or psoriasis, excessive patient-staff contact as may occur in intensive care, and the use of invasive devices for vascular and ventilatory access.
Colonisation of healthy individuals is uncommon and transient, and rarely leads to invasive disease.
It is hard to eradicate MRSA colonisation from a healthcare facility where its presence has become endemic. However, epidemic infections are often superimposed on an endemic background, and these can be usefully prevented and controlled by everyday infection control practices and special control measures. Routine measures such as hand washing, environmental cleanliness and rational antibiotic prescribing should be vigorously promoted, since these significantly reduce the likelihood of hospital acquired infections generally. Special control measures such as isolation, cohort nursing, screening for carriage and eradication of carriage in patients and staff are expensive, disruptive and difficult to implement, but have their place during outbreak situations or in special clinical areas. Hospital and community infection control teams should make careful risk assessments of their local situations and recommend special control measures as appropriate. Measures such as pre-admission screening of patients, screening of staff and treatment aimed at eradication of carriage may be appropriate in an organ transplant or prosthetic joint implantation setting, but not in an acute admissions unit or a long-term elderly care facility. One policy does not fit all.
References
- Spink WW, Ferris V. Quantitative action of penicillin inhibitor from penicillin resistant strains of Staphylococci. Science 1945; 102:221.
- Barber M. Methicillin resistant Staphylococci. J Clin Pathol 1961; 14:385.
- Moellering RC. Linezolid: the first oxazolidinone antimicrobial. Ann Intern Med 2003; 138:135-42.
- Pujal M, Pena C, Pellares R et al. Nosocomial Staphylococcus aureus bacteraemia among nasal carriers of methicillin resistant and methicillin susceptible strains. Am J Med 1996; 100:509-16.
