The role of perioperative care in reducing rates of methicillin resistant Staphylococcus aureus.
Abstract: Methicillin resistant Staphylococcus aureus (MRSA) is defined as any strain of Staphylococcus aureus resistant to beta-lactam antibiotics, including the penicillins and cephalosporins. Over the past ten years the UK has seen a dramatic increase in MRSA prevalence in healthcare facilities and the community, with an estimated 30-50% of healthy adults thought to be colonised with MRSA. Surgical patients are among those at highest risk. With potential sequelae including septicaemia, septic shock, septic arthritis, osteomyelitis, meningitis, pneumonia or endocarditis, it is vital that all care facilities have up to date evidence-based guidelines to tackle this problem. The purpose of this review is to highlight the current evidence supporting some of the key perioperative measures which may be implemented in preventing MRSA.

KEYWORDS Perioperative care / Methicillin resistant Staphylococcus aureus / MRSA / Antibiotic resistance Provenance and Peer review: Unsolicited contribution; Peer reviewed; Accepted for publication June 2011.
Article Type: Report
Subject: Drug resistance in microorganisms (Development and progression)
Evidence-based medicine (Health aspects)
Evidence-based medicine (Research)
Staphylococcus aureus (Physiological aspects)
Staphylococcus aureus (Research)
Beta lactamases (Health aspects)
Beta lactamases (Research)
Authors: Byrne, Clare
Hazlerigg, Alexandra
Khan, Wasim
Smitham, Peter
Pub Date: 12/01/2011
Publication: Name: Journal of Perioperative Practice Publisher: Association for Perioperative Practice Audience: Academic Format: Magazine/Journal Subject: Health; Health care industry Copyright: COPYRIGHT 2011 Association for Perioperative Practice ISSN: 1750-4589
Issue: Date: Dec, 2011 Source Volume: 21 Source Issue: 12
Topic: Event Code: 310 Science & research
Geographic: Geographic Scope: United Kingdom Geographic Code: 4EUUK United Kingdom
Accession Number: 274700156
Full Text: Methicillin resistant Staphylococcus aureus (MRSA) is defined as any strain of Staphylococcus aureus resistant to betalactam antibiotics, including the penicillins and cephalosporins (Livermore 2000). Strains of MRSA have acquired the mecA gene, which encodes an altered penicillin binding protein (PBP 2a) and this causes the resistance. Occasionally it also causes resistance to other antibiotics (Ayliffe 1974).

The prevalence of MRSA in healthcare facilities and the community has increased dramatically in the UK over the past 10 years (Gemmell et al 2006). In care settings this rise has been blamed on staff shortages, patient overcrowding, inadequate staff training, lack of isolation facilities, inattention to infection control procedures and the frequent relocation of staff and patients (New Zealand Ministry of Health 2002). Risk factors for the development of MRSA include older age, previous hospitalisation, skin disease, intravenous drug abuse, ventilation, dialysis, prolonged hospitalisation or residence in long-term care facilities, and the presence of indwelling catheters or other medical devices (Waldvogel 1995, Laibl Rogers 2005, Wyllie et al 2005). In the community, acquisition from household contacts and 'silent' acquisition in healthcare settings associated with inpatient care lasting over five days in the previous year seem to be the most prominent causative factors (Calfee et al 2003, Jernigan et al 2003, Salgado et al 2003, Tacconelli et al 2004).

Patients may be colonised or infected with MRSA. Those colonised with MRSA are generally asymptomatic while MRSA is being carried on or in the body without causing illness. Infection with MRSA means the patient is symptomatic, and this may range from a superficial wound infection to sepsis, bacteraemia and even death. It is possible to be colonised with MRSA, which does not progress to infection (Coello et al 1997), however these patients may be at an increased risk of developing infection (Pujol et al 1994). Risk factors for developing clinical infection with MRSA include staying in intensive care units, administration of three or more antibiotics, presence of ulcers, surgical wounds, nasogastric or endotrachial tubes, drains, and urinary or intravenous catheterisation. Intravenous cannulation is an independent risk factor for the development of infection (Pujol et al 1994). Once established, MRSA is difficult to control and its survival is increased by antibiotic use (Burnett et al 1980, Boyce 1989, Schentag et al 1998, Manian et al 2003). Changes in antibiotic prophylaxis and treatment may lead to selection of new clones of MRSA and subsequent resistance. However, the evolution and spread of resistance is not well described. Therefore, antibiotic use must adapt gradually with national and local changes in prevalence in order to avoid the selection of new clones (Gemmell et al 2006).

MRSA infection has been shown to increase morbidity and mortality. Deaths mentioning MRSA are higher among males than females. In 2006 the office for National Statistics quoted male deaths with MRSA mentioned on their certificate at 26.8 per million population; for females in 2008 this was 10.3 per million. There is extensive guidance issued by the Department of Health (DH), the National Institute for Health and Clinical Excellence (NICE) and the Association for Perioperative Practice (AfPP) that helps to guide current clinical practice. The added morbidity and prolonged hospital stay have a significant cost implication. Estimates have been quoted for the NHS spending an extra 1 billion pounds per year on hospital acquired infections (HAI) (National Audit Office 2009).

MRSA is the cause of a significant number of HAIs, and has been isolated from nearly a quarter of all surgical site infections (SSI) (AfPP 2007). Additional costs of SSI alone have been estimated to be between 814 [pounds sterling] and 6626 [pounds sterling] per patient (NICE 2003), and this is increased to an estimated 9000 per [pounds sterling] patient when the SSI has been caused by MRSA (Wernitz et al 2005, Wendin 2008). The additional costs can be attributed to extra nursing care, barrier requirements, reoperation and medications. The potential litigation costs from patient dissatisfaction and reduced quality of life costs has not been fully established (NICE 2003). Since 2003-2004 The National Audit Office estimates that the Department of Health and associated bodies have spent 57 million [pounds sterling] on initiatives to tackle HAIs throughout the UK, as well as 63 million [pounds sterling] as a single payment for the deep clean in 2007-2008.

Areas commonly colonised with MRSA include the nostrils, respiratory tract, urinary tract, wounds and sites of intravenous catheters. Presentation depends on the area affected. In the case of skin colonisation, patients may present with red, warm, tender skin with pus, boils, abscesses, styes, carbuncles, cellulitis or impetigo (Iyer & Jones 2004). Fever, increased peripheral white blood cell count, increased inflammatory markers e.g. Creactive protein (CRP), ulcers and sores are also indicative of MRSA infection. However, MRSA is not limited to the skin and once the infection enters the blood stream septicaemia, septic shock, septic arthritis, osteomyelitis, meningitis, pneumonia or endocarditis may arise.

Screening for MRSA and decolonisation regimes

An estimated 30-50% of healthy adults are colonised with MRSA (Laibl Rogers 2005). With an estimated 22% mortality rate from MRSA bacteraemia (Selvey et al 2000), it is essential that we identify and treat those who are MRSA positive. Ideally all patients and staff should be routinely screened for MRSA. In reality this is rarely possible due to budget and staffing constraints, and staff turnover.

All patients awaiting an elective operation require preoperative screening. This may be carried out either in preadmission clinics or by general practitioners. Ideally screening should be performed as close to the operation date as possible. Some hospital admission patients are not required to undergo screening e.g. those requiring pregnancy termination, eye surgery or those being admitted to mental health trusts (DH 2006). Emergency admissions are screened on the ward at admission. Those patients known to be at high risk, for example care or residential home patients, patients who have had previous positive Staphylococcus aureus blood cultures, or those who have been transferred from another hospital, are put in a side room and barrier nursed until they have been screened and MRSA colonisation has been excluded (DH 2007). Intravenous drug abusers, HIV positive patients and those involved in contact sports may also warrant regular screening (Coia et al 2006).

Once MRSA has been isolated from the swab a decolonisation regime is adopted. This decolonisation regime is to reduce the MRSA to a sub detection level and should ideally be done five days prior to the operation as the regime is limited in its duration of effectiveness. The admitting ward should be notified of the preadmission candidate who has undergone a decolonisation regime as only suppression rather than complete eradication of MRSA may have been achieved. A typical decolonisation regime for a positive nasal swab would consist of topical application to the inner surface of each nostril of 2% mupirocin three times a day for five days. If a preoperative assessment has revealed a patient to be a carrier of MRSA on their skin, a shampoo body wash of 4% chlorhexidine gluconate is applied to identified carriage sites e.g. axilla, groin or perineum. Successful suppression is confirmed by three additional screens each taken a week apart, beginning at least two days after the regime has been completed (DH 2007).

All high-risk patients should be screened on admission and at regular intervals during their hospital stay depending on local infection control protocols, unless they are being directly admitted to isolation with no plan to clear them of MRSA carriage. Samples should be taken from nostril, skin lesions, wounds, groin/perineum, sites of intravenous and urinary catheters, tracheostomy sites and the umbilicus in neonates. In those with a productive cough, sputum may also be tested (Coia et al 2006). This approach to the screening of surgical patients may decrease MRSA infections by facilitating the appropriate selection of antibiotic agents for preoperative prophylaxis (Zanetti et al 2001, Stephan et al 2008).

Almost 70% of all cases of MRSA bacteraemia occur in surgical or emergency medical patients (Wyllie et al 2005). SSIs may take either of two forms; the most common is colonisation of the operative field during surgery, and an alternative source is haematogenous seeding during sepsis/bacteraemia (Wilson et al 1975). It comes as no surprise then that units deemed to carry a high risk of MRSA infections or colonisation include ICU, transplant wards, and cardiothoracic, vascular surgery, trauma and orthopaedic surgery. These wards typically treat many patients with additional risk factors, including: being over 60 years of age or diabetic, having ulcers or urinary catheters. These groups account for over 70% of cases (Gemmell et al 2006). Oncology, haematology and renal care wards are also classed as high risk (Wyllie et al 2005).

Treatment for MRSA

In an outbreak of MRSA infection, surgical and intensive care patients should be prioritised. In order to prevent the development of MRSA infection in such patients it has been recommended that those who are colonised or who have been identified as having one or more of the risk factors for progression to infection receive early treatment with vancomycin. This has been shown to decrease mortality (Coello et al 1997).


The decision of how to treat MRSA infection and colonisation depends largely on local patterns of resistance. Current research supports the use of local guidelines, and an example is summarised in Figure 1. However a UK multicentre study carried out in the period 2001-2003 found that:

* 92% and 72% of strains were resistant to fluoroquinolones and macrolides respectively.

* Most isolates were susceptible to tetracyclines, fusidic acid, rifampicin and gentamicin.

* 12% of tested strains were mupirocin-resistant 591.

* 50% of treatment regimens used included a glycopeptide alone or with other agents.

* In bacteraemic patients the rates of resistance to tetracyclines, macrolides and rifampicin appeared to be lower than previously reported.

BSAC 2005

Based on the current literature there is insufficient evidence to suggest whether topical, systemic or combination therapy is the best form of treatment to use (Speller et al 1997).

Drug resistant MRSA infections increase with increased exposure to antibiotics particularly at low concentrations (Ubukata et al 1989). It has been shown that the efficacy of beta-lactam antibiotics is dependant on the length of time they remain above the minimum inhibition concentration (MIC) (Craig 1998). It is therefore advisable to administer such antibiotics at lower doses regularly e.g. every three hours, rather than one higher dose to keep levels over their MIC (Kato et al 2006).

Much debate surrounds when and for how long antibiotics should be administered. Nelson et al (1983) conducted a study comparing the efficacy of administering antibiotics for one or seven days postoperatively and found no difference in infection rates between the regimens. Similarly another study found no difference in infection rates after one or three days of antibiotic treatment (Williams & Gustilo 1984). It has therefore been recommended that postoperative antibiotic prophylaxis be limited to 24 hours after surgery (Kato et al 2006).


Prevention of MRSA

The primary form of MRSA spread is handborne transmission from the colonised hands of healthcare workers (Mulligan et al 1993). Hand washing is the most effective way of preventing the spread of MRSA (AfPP 2007) . MRSA can survive for months on surfaces such as equipment, floors and furniture. As such there is a transmission cycle of MRSA from the infected bedside cabinets surrounding the patient to healthcare workers' hands and even to those of the patients. Standard principles for preventing hospital-acquired infections should be implemented to prevent the transmission of MRSA (Figure 2). The hospital environment must be clean, equipment should be thoroughly cleaned between patients, waste and laundry must be correctly handled, and all staff must be adequately trained in hospital hygiene protocols particularly in relation to hand hygiene, the use of personal protective equipment and the safe use and disposal of sharps (NICE 2003).

While not intended to substitute for good theatre practice, patient optimisation may aid in decreasing infection rates by optimising natural host defences against infection. As most pathogens originate from skin flora, by decreasing the time that a patient is exposed to pathogens in the hospital environment and by screening and decontaminating surgical patients, infections rates could be further lowered (Dohmen & Konertz 2007).

An attempt should be made to reduce immunosuppressants preoperatively and discontinue if possible until after surgery (Dohmen & Konertz 2007). Diabetics have a markedly increased rate of SSIs. Blood glucose levels of >300mg/dL increase the odds of developing a SSI from 2.54 to 3.32 in comparison with those patients with blood glucose of <250mg/dL. Therefore an attempt should be made to monitor and control the blood glucose levels of all diabetic patients undergoing surgery (Dhinsa et al 2010). Perioperatively, the use of continuous insulin infusion was found to be superior to subcutaneous insulin (Dohmen & Konertz 2007).

Preoperative strategies

There is evidence that preoperative showering one or two days before surgery, with soap decreases the skins bacterial burden however there is no evidence of a significant decrease in postoperative infections. NICE guidance advises that preoperative showering with chlorhexidine is not a cost-effective intervention to reduce SSI, and a Cochrane review showed that there was no significant reduction in SSI after using chlorhexidine (Webster & Osborne 2011). In addition the authors recognise the risk that repeated chlorhexidine washing may encourage the development of resistant strains.

Preoperative hair removal is sometimes necessary in order to provide a clear operative field and allow a more effective seal from the surgical dressing. Shaving of surgical sites may increase the risk of infection due to the formation of microabrasions. Evidence has shown that patients who receive any form of preoperative hair removal suffer higher rates of SSIs than those patients who receive none (Winston 1992). It is therefore recommended that in cases where hair removal is necessary, electric clipping or depilatory cream be used as close to the time of surgery as possible to provide the best chance of decreasing SSIs (Cruse & Foord 1973, Ayliffe et al 1983, Leigh et al 1983, Ayliffe 1984, Masterson et al 1984, Rotter et al 1988).

Prior to the patient coming to theatre, theatre staff should have been notified of carriers and those who are infected with MRSA. Staff should be instructed on the appropriate procedures to minimise exposure. Typically the MRSA patient will be placed last on the list to cause the least disruption, and minimise cross contamination. If this is not viable then time for extra air exchanges before the next patient should be allowed (Coia et al 2006, AAGBI 2008).

In the anaesthetic room, certain precautions must be carried out to reduce contamination or spread of MRSA, and to minimise the risk of infection. Prophylactic antibiotics have been shown to reduce SSI (Barker 2002). The inclusion of this criterion on the World Health Organisation (WHO) Time Out Form has increased administration compliance from 65% to 97% (Rosenberg et al 2008). Appropriate antibiotic prophylaxis should be administered between 30-60 minutes before the incision and before the tourniquet has been inflated. This is because the effectiveness of the antibiotic is reliant on adequate tissue levels at the time of incision. Prophylactic antibiotics should be discontinued within 24 hours of the procedure, and typically for most outpatient procedures it will be a single dose administration. Vancomycin 1g intravenously has been advocated if the patient is considered high risk. Special considerations surrounding the dosing of prophylactic antibiotics with the exception of vancomycin include cases where the duration of surgery exceeds four hours or where blood loss has exceeded 1500ml (Cosgrove & Avdic 2011).

Typically the MRSA patient will be anaesthetised and recovered in theatre. To protect other patients, disposable anaesthetic circuits are used, and the disposal of these circuits is categorised as clinical waste. Equipment for terminal disinfection e.g. laryngoscope blades are also disposed of. Intravenous cannulation, an independent risk factor for developing infection (Pujol et al 1994), should be performed using the 'non touch' technique (Pratt et al 2007). The theatre must be cleared of any surplus equipment. Reducing people traffic has been shown to reduce rates of infection (Babkin et al 2007, Olsen et al 2008). Signs should be visible to notify colleagues and doors shut in order to reduce unnecessary thoroughfare through the operating theatre. The patient's trolley must remain inside the anaesthetic room, and all participating staff and portering staff in contact with the patient should be wearing protective clothing including donning gloves and plastic aprons (AfPP 2007). A study showed that during routine patient care the rate of detection of MRSA on gowns and/or gloves was 18% (Snyder et al 2008).

Intraoperative strategies

Theatre environment

Laminar airflow systems are used in many theatres to reduce the occurrence of infections. They are expensive to install and maintain (Kirkland et al 1999, Merle et al 2000, Coello et al 2005). Their use is based on the assumption that they are successful in decreasing the number of SSIs. However, few controlled studies have been performed to back up this assumption. One recent study found an increase in the number of SSIs associated with the use of laminar flow theatres (Brandt et al 2008). In order to justify their cost and to determine the efficacy of laminar airflow devices more randomised control trials are required.

Hypothermia results in vasoconstriction and decreased functioning of the immune system, and this increases the chance of developing an SSI. It has been shown that a decrease of 1.5 degrees centigrade from a patient's body temperature during surgery increases the risk of postoperative infection. Thus by monitoring a patient's temperature, using simple measures such as extra blankets and increasing the air temperature of theatres, infection rates may be lowered (Kurz et al 1996, Mahoney & Odom 1999, Melling et al 2001, Dohmen & Konertz 2007).

Hand hygiene, gloves and facemasks

It is recommended that those scrubbing use hand wash for five minutes followed by three minutes of disinfection with alcohol disinfectant (Mangram et al 1999). As surgical gloves are not totally fluid proof, wearing double gloves may be recommended in certain cases for the scrub team (Doyle et al 1992). There is no evidence that the use of surgical masks decreases infections. However, they do provide protection for the wearer and, due to theoretical rationale, it is not unreasonable for all those present in theatre to wear masks (Mangram et al 1999).

The choice of aqueous surgical scrub has in many hospitals previously been left to the surgeons' preference, with the main choice being between a water based solution containing chlorhexidine gluconate or a providone iodine scrub. Chlorhexidine has been shown to be superior to iodine scrubs in reducing colony forming units (CFUs) (Pereira et al 1990, Furukawa et al 2005). A Cochrane Review on surgical hand asepsis showed that alcohol rubs containing 6090% ethanol, isopropanol or n-propanol were as effective as the aqueous scrubs in preventing SSI (Tanner et al 2008).

Surgical gowns, drapes and linens

All material should have a pore size of <20 m. Materials in the surgical field should be waterproof, sterile and preferably disposable (Mitchell et al 1978). Antiseptic preparation of a patient's skin prior to surgery is an important aseptic precaution, however, antiseptic solutions can wash off during surgery potentially permitting bacterial re-growth. The use of plastic adhesive barrier drapes has been shown to reduce wound contamination but not to significantly reduce skin flora. These drapes may be impregnated with iodine or other antiseptic agents (Dohmen & Konertz 2007). While there is no evidence of associated negative outcomes, there is some but insufficient evidence that the use of incisional drapes with or without iodine or other antiseptic products decreases infection rates (Fairclough et al 1986, Dewan et al 1987, Yoshimura et al 2003, Segers et al 2007, Parks et al 2007, Kramer et al 2010).

Agents used to prepare patients' skin preoperatively should ideally be broad-spectrum, ready-to-use-dilutions, in single use containers to avoid contamination. Alcohol based solutions have been found to be most effective. While complete decontamination is impossible, such solutions can effectively reduce resident flora (Lilly et al 1979, Kampf & Kramer 2004). Chlorhexidine gluconate compares favourably to iodine in several studies, showing a reduced SSI rate (Darouiche et al 2010) and better elimination of bacteria (Ostrander et al 2005).

Surgical wound

Carefully sutured wounds seal with fibrin within 6-24 hours protecting them from moisture and bacterial contamination (Kato et al 2006). Although more expensive, several studies have shown a decrease in the number of SSIs when antibiotic coated sutures are used (Fleck et al 2007, Justinger et al 2009). The use of such sutures in combating MRSA infection is supported by a study examining their ability to inhibit the colonisation of bacteria after direct in vivo inoculation with Staphylococcus aureus.

Although carried out on a guinea pig model, this study demonstrated a significant decrease (p<0.05) in infections when antimicrobial sutures were compared with standard sutures (Storch et al 2004). Microbial sealants mechanically block the passage of pathogens into the surgical wound. While early clinical results are promising, particularly when combined with a topical iodine skin preparation, more studies are required before this method can be introduced into good surgical practice (Dohmen & Konertz 2007, Wilson 2008).

Operative oxygenation

The most important immune defence against surgical pathogens are neutrophils. Neutrophils play a vital role in the immune defence against SSIs and are mediated by oxidative killing. They are dependent on the production of bactericidal superoxide radicals from molecular oxygen and on the partial pressure of oxygen to function adequately (Barbior 1978). The regulation of angiogenesis is also dependant on such factors (Hopf et al 1997). There is evidence that by using 80% oxygen instead of 30% oxygen during surgery and also using supplementary oxygen during recovery, postoperative infection rates can be lowered by as much as 50% (Greif et al 2000, Pryor et al 2004, O'Connor 2004, Belda et al 2005, Dohmen & Konertz 2007, Velazquez 2007).

Postoperative strategies

The Health Protection Agency found that, between April 2006 and December 2009, 44% of MRSA cases established while patients were staying in acute trusts were attributable to lines (DH 2006). 18% were from intravenous cannulas and 19% from central lines. Early removal of all surplus lines postoperatively is advised. Soft tissue infections and skin infections were found to be the source in a further 40% of cases. Antimicrobial gauze replacing sterile plain gauze reduced the MRSA SSI rate by 47% (Mueller & Le 2008). Commercially available silver coated dressings, such as Acticoat, have been developed for the treatment and prevention of MRSA infection (Ulkur et al 2005, Ip et al 2006, Lee et al 2010). More studies on their efficacy and how often the dressings need to be replaced along with cost analysis need to be performed, and consideration needs to be given to the potential resistance these dressing may encourage.


In summary there is much controversy over the best approach to tackling the problem of MRSA. While targeted active surveillance is best reserved for high-risk patients or during times of an outbreak, adopting the simple perioperative practices discussed in this review can lower the incidence of MRSA infection and in turn its emergent resistance.


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Clare Byrne BSc(Hons)

Medical student (4th year), University of Aberdeen

Alexandra F Hazlerigg MBBS, BSc, MRCS

Speciality Doctor, Trauma and Orthopaedics, Kingston Hospital, Kingston upon Thames

Wasim Khan MBChB, MSc, MRCS, PhD

Academic Clinical Fellow, UCL Institute of Orthopaedic and Musculoskeletal Science, Royal National Orthopaedic Hospital, Stanmore

Peter Smitham MBBS, MRCS, PhD

Clinical Lecturer, UCL Institute of Orthopaedic and Musculoskeletal Science, Royal National Orthopaedic Hospital, Stanmore

No competing interests declared

Correspondence address: Wasim Khan, UCL Institute of Orthopaedic and Musculoskeletal Science, Royal National Orthopaedic Hospital, Stanmore, Middlesex, HA7 4LP.

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