MRSA: diagnosis, screening and management

Staphylococcus aureus (S. aureus) is a common gram-positive bacterium that colonises human skin and mucous membranes​[1]​. It is usually a harmless member of the skin flora; however, infection can occur if there is a breach to the skin or mucosal barrier, followed by tissue invasion and damage​[2]​. While it frequently causes skin and soft tissue infections (accounting for up to 80% of pathogen-positive specimens), S. aureus can more rarely result in life-threatening infections, such as bacteraemia (i.e. blood stream infection), with population incidence estimates ranging from 10–30 per 100,000 person-years among high income countries​[3–5]​.

Colonisation and infection are two different states, and it is important to differentiate between them. When bacteria exist within an environment such as the mouth, skin or airway without causing disease, the host is said to be colonised. If the pathogen invades the host’s tissues and multiplies, the host is infected with the pathogen​[5]​.

Most strains of S. aureus are sensitive to methicillin, a penicillin antibiotic. Methicillin use was replaced with alternative penicillin antibiotics with better stability and side effect profiles around 1982; however, the terms methicillin-sensitive or methicillin-resistant continue to be used to describe the susceptibility of S. aureus to penicillin​[6–8]​.

A 2021 report highlighted the potential effect of the COVID-19 pandemic on the incidence of hospital-onset methicillin-resistant S. aureus (MRSA) bacteraemia in England. While the proportion of all S. aureus bacteraemia caused by MRSA reduced to 5.6% (April 2020 to March 2021) in England, compared with 6.2% the previous year, the annual incidence rate of hospital-onset MRSA bacteraemia increased by 35.5% (from 0.8 to 1.0 per 100,000 bed-days) — the largest annual increase since enhanced surveillance began in 2007​[9]​. The reasons for this are being investigated but the greatest increase seems to correlate with the second wave of COVID-19 cases in England (January to March 2021)​[10]​.

MRSA bacteria are easily transmitted in healthcare settings and infections have limited treatment options​[11,12]​. Prevention is therefore important to reduce the impact on patient outcomes and length of hospital stays, and healthcare professionals should understand the diagnosis, screening, and management of MRSA-colonised and MRSA-infected patients.

Pharmacists and pharmacy staff can reduce the spread of MRSA by encouraging prudent antimicrobial use, providing education on local MRSA policies and adherence to local infection prevention and control (IPC) guidance​[13]​.  

Epidemiology

In the 1990s, MRSA accounted for 34% of S. aureus bacteraemia isolates in UK microbiology laboratories​[14]​. In 1998, national guidelines for controlling MRSA were published, which covered screening, isolation and hand hygiene, bringing standard infection control policies into healthcare settings​[11]​. Despite these measures, by 2002, the UK had the second highest MRSA rate in Europe, with an estimated 44% of S. aureus isolates identified as MRSA​[15]​. Mandatory surveillance of MRSA was introduced in 2001 and was enhanced in 2007 to collect demographic, clinical and epidemiological information on each case​[9]​. Since then, the incidence of MRSA bacteraemia has reduced significantly (see Figure 1)​[10]​.

In 2013, NHS England introduced a “zero tolerance” approach to MRSA bacteraemia​[16]​. This approach resulted in it being compulsory to report cases of MRSA bacteraemia to Public Health England and conduct a root cause analysis (RCA) (also known as a post-infection review) for each case. The RCA panel consists of all organisations involved in the patient’s care pathway to jointly identify any lapses of care and areas for improvement, as well as agreeing on actions to prevent recurrence​[17]​. The main components examined in an RCA are contributing factors in screening for colonisation, devices used by patient, antimicrobial therapy, skin integrity, transmission, hand hygiene, environment, and organisational and governance issues​[17]​.

From 2018, MRSA bacteraemia reporting has only been mandatory for trusts and clinical commissioning groups with the highest MRSA rates​[16]​. Pharmacists in primary and secondary care should support the preparation of RCAs by reviewing the appropriateness of antimicrobial prescribing (e.g. choice, dosage and duration) as well as providing information on MRSA decolonisation therapy, depending on patient eligibility. The panel will ensure that learning and good practice from reviews are shared with wider clinical teams. For example, if a contributing factor is inappropriate antimicrobial prescribing, the pharmacist on the panel should cascade this within the pharmacy department and clinical team who look after the patient, and stipulate any actions to prevent recurrence. The department will also be expected to undertake an audit on antimicrobial prescribing​[17]​.

Infection, prevention and control measures

MRSA is now considered endemic in healthcare settings, especially in areas deemed high-risk (e.g. intensive care, vascular, burns and orthopaedic units). Patients with indwelling medical devices, trauma or surgical wounds are deemed at greater risk of colonisation or infection​[18,19]​. The most common route of MRSA transmission in healthcare settings is through healthcare workers, who acquire the organism from direct contact with patients who are either colonised or infected with MRSA​[11]​. Rarer routes of transmission include touching patient’s skin, or via inanimate objects or environmental surfaces (e.g. clothing, bedding, the area around a patient’s bed or a patient’s bathroom)​[19]​. Effective hand hygiene is the cornerstone of good IPC measures. Hand washing with soap and water, or use of alcohol sanitiser, and covering cuts or abrasions with a waterproof dressing are all advised. Pharmacists and their teams should be aware of the five moments of hand hygiene (see Figure 2), follow the IPC recommendations in their daily practice and challenge others who are not adhering to this guidance​[20]​. Other IPC strategies for managing patients colonised or infected with MRSA include barrier nursing the patient with single-use gloves and aprons, and isolating the patient in a side room (whenever possible)​[19]​.

Detection of patients colonised or infected with MRSA

Detection of colonised patients

MRSA colonisation is detected through microbiological screening. Details of patients recommended for screening can be seen in Box 1​[18,21]​. Some trusts may have additional patient groups who require screening. Local risk assessments should be used to define other potential high MRSA-risk units/specialties (e.g. transplant, neonatal) and units with a history of high endemicity of MRSA; therefore, local policy should be consulted​[21]​.

Microbiological screening often involves nasal screening because the anterior nares are the most frequently colonised site. However, areas of damaged skin should also be screened. Recommendations for further screening sites (e.g. groin, axilla, and perineum) vary between national and local guidelines; therefore, local policy should be consulted​[22,23]​.

Various microbiological methods may be used to detect MRSA in screening specimens. The first laboratory stage involves selectively culturing methicillin-resistant strains (via direct or enrichment culture, most frequently with a chromogenic selective MRSA medium, or, alternatively, molecular methods). This is followed by the ‘identification’ stage, which must, as a minimum, identify a S.aureus species and demonstrate resistance to the antibiotic cefoxitin prior to reporting the result​[24]​.

Often, there is an alert system within the organisation that allows healthcare professionals to identify patients with a history of MRSA colonisation or infection; it is important to be familiar with the local alert system when reviewing patients’ antimicrobial therapy to ensure that MRSA decolonisation is prescribed when indicated.

Detection of MRSA-infected patients

To detect MRSA, a clinical sample must be taken from the patient and sent to the laboratory. The sample type taken may correlate specifically with the suspected clinical infection syndrome or it may have been taken as part of a ‘septic screen’. For example, blood cultures must be taken within an hour of identifying suspected sepsis, additional information on which can be found here​[25]​.

S. aureus can be cultured from a variety of samples, including blood, pus, sputum, urine and other specimens, such as joint fluid aspirates, depending on the suspected source of infection​[26]​. Organisms that have grown and been identified as S. aureus will undergo antimicrobial susceptibility testing, which may then identify the organism as MRSA​[27,28]​.

MRSA infection is clinically indistinguishable from MSSA (methicillin-susceptible S. aureus) infection, however, it has a stronger association with hospital-acquired infections than MSSA and case fatality ratios tend to be higher for MRSA bacteraemia compared with MSSA bacteraemia​[29,30]​. MRSA infection is more likely in patients with:

• Recent hospitalisation or invasive devices, such as urinary catheters;
• Previous (or current) MRSA infection or colonisation;
• Residence in long-term care facilities;
• Previous antibiotic use;
• Intravenous drug use;
• No response to first-line antibiotics;
• Recurrent skin or soft tissue infections, or a chronic non-healing ulcer, especially if purulent​[18]​.

What action should be taken when infection is suspected?

Depending on the clinical infection syndrome suspected and the severity of clinical illness, empirical antibiotics may be started based on local microbiological guidelines for the suspected syndrome. Ideally, clinical sampling should be performed before starting antibiotics to ensure better microbiological culture yield. In patients known to be colonised with MRSA or thought to be at high risk of MRSA infection, clinicians may opt for antibiotics that cover MRSA prior to receiving any culture/sensitivity results. Where laboratory confirmation has occurred and MRSA is believed to be the most likely culprit pathogen, effective treatment regimens should cover MRSA.

Nasal and skin decolonisation

MRSA decolonisation is not routinely required for asymptomatic carriers of MRSA in the community. However, if a patient colonised with MRSA is undergoing a high-risk surgery (see Box 1) they should receive skin and nasal decolonisation to reduce the MRSA burden. This can minimise the risk of surgical site infection and reduce transmission to other patients​[18,31]​.

The successful eradication of MRSA is not possible every time; however, any reduction in bacterial load will reduce the risk of endogenous infection or transmission to other patients​[32]​. Local policy should be observed for re-screening post-decolonisation and for repeated decolonisation.

In clinical practice, the choice and duration of skin and nasal products will vary with local guidance and should consider:

• The type of procedure;
• Individual patient risk factors, including allergy;
• Patients with carers or live-in relatives who have a severe allergy to any of the product ingredients (specifically arachis oil), as they should not be given the respective products;
• The risk of severe chemical injuries with the use of chlorhexidine (both alcohol-based and aqueous solutions) in preterm babies (an alternative is an alcohol-based solution of povidone-iodine);
• The potential impact of infection on the individual patient, including the cost of managing the infection;
• Local formulary and resistance pattern​[33]​.

Nasal decolonisation

The National Institute for Health and Care Excellence (NICE) recommends nasal mupirocin ointment in combination with a chlorhexidine body wash before procedures in which S. aureus can potentially cause surgical site infection​[33]​. Neomycin/chlorhexidine nasal cream can also be used for patients with mupirocin resistant MRSA or allergy to an ingredient in mupirocin ointment (see Box 2 for dosing information)​[34]​. Counselling points for the administration of nasal ointments and creams can be found here. 

Skin decolonisation

Skin cleansers are used in combination with nasal ointment for MRSA skin decolonisation; chlorhexidine 4% skin cleanser is the most common​[37]​. Individual product information should be consulted for advice on how to use the products, including contact time. 

Cleansers should not be used on cuts or areas of broken skin. It is important to consider the side effects of the cleanser; for example, chlorhexidine 4% may cause irritation or chemical burns in patients with existing skin conditions and in preterm babies​[33,38]​.

The fragrance in one of the chlorhexidine 4% cleanser formulations has recently changed, and the product now contains soya oil. The manufacturer now advises against using this product for patients with peanut and soya allergies​[37]​.

The most common side effect of nasal and skin products are skin reactions. Patients should stop using the product and inform relevant healthcare professionals if this happens​[34]​.

As part of decolonisation counselling, patients should be advised:

• How to use the products;
• The importance of using clean wash cloths and clean dry towels;
• To change into clean clothing after the wash;
• To change bedding daily while using the decolonisation products;
• What to do if allergy, adverse reaction or side effects occur​[34]​.  

Surgical prophylaxis for MRSA-colonised patients

Antibiotic prophylaxis should be given to patients undergoing any surgery that is not defined as ‘clean non-prosthetic uncomplicated surgery’, according to NICE guidelines​[33]​. For patients who are MRSA-colonised, the prophylactic antibiotic(s) chosen must cover MRSA in addition to the standard spectrum of cover, which usually includes both gram-positive and gram-negative cover but excludes MRSA.

Local antibiotic guidelines for surgical prophylaxis should therefore always provide an alternative (to the standard) regimen used for MRSA-colonised patients. Most commonly, intravenous teicoplanin is used.

It is important to ensure that the indication is clearly stated when prescribed, as surgical prophylaxis (including MRSA cover for a colonised patient) may require a single dose, avoiding the incorrect assumption that a treatment course may be required. This is an important opportunity to prevent possible overuse of antibiotics.

Treatment of MRSA infection

Vancomycin and teicoplanin (both given parenterally) remain the antibiotics of choice for treatment of MRSA infection​[12]​. They are glycopeptide antibiotics that are active against most gram-positive microorganisms. Vancomycin has a narrow therapeutic range (trough level of 10–20mg/L). For deep-seated infection, such as meningitis and bone and joint infection, a trough level of 15–20mg/L is recommended to achieve clinical effectiveness​[12,39]​. Levels above this range can cause toxicity — including nephrotoxicity and ototoxicity — while sub-therapeutic levels can lead to treatment failure and contribute to antimicrobial resistance (AMR)​[39,40]​. Consequently, therapeutic drug monitoring (TDM) of vancomycin and appropriate dose adjustments are paramount, especially for patients with a life-threatening MRSA infection. Teicoplanin has a wider therapeutic range (trough levels vary based on indication, see guidelines for more information) and the use of TDM for this drug varies between trusts​[40]​.  

Pharmacists should be able to undertake TDM to optimise a patient’s therapy to minimise the risk of adverse reactions​[12,13]​. Local prescribing guidelines should be used for dosing guidance and target therapeutic levels for vancomycin and teicoplanin.

Other antibiotics used for the management of MRSA are selected based on the organism’s sensitivity pattern, but may include linezolid, co-trimoxazole, daptomycin, clindamycin, rifampicin, ciprofloxacin and delafloxacin​[12,13]​. For each of these antibiotics, the cautions, contraindications, interactions and monitoring (where appropriate) should be considered. The updated 2021 BSAC guidelines recommend treatment regimens for various types of MRSA infection​[12]​.

Adherence is vital and patients should be involved in the decision-making process. Information relating to adherence advice can be found here​[41]​.

Antimicrobial stewardship and MRSA

Globally, around 700,000 deaths each year are associated with AMR and, without intervention, mortality is estimated to reach 10 million by 2050​[42]​. A multidisciplinary approach is necessary to preserve the effectiveness of antimicrobials and reduce the transmission of infection​[13,43,44]​. Antimicrobial stewardship involves selecting an appropriate antimicrobial, and optimising its dose and duration while minimising toxicity is crucial. Pharmacists and pharmacy technicians in all sectors should be able to confidently review the appropriateness of antimicrobial prescriptions to prevent AMR. More information on how this can be done in practice can be found in ‘How to evaluate the clinical appropriateness of an antimicrobial’. Box 3 explores this role and outlines best practice in the context of MRSA.

Summary

MRSA bacteria are easily transmitted in healthcare settings and have significant impact on patient outcomes, length of hospital stay and healthcare cost. It is therefore important for healthcare professionals to understand the diagnosis, screening and management of MRSA-colonised and MRSA-infected patients, in combination with IPC guidance, and apply these to day-to-day practice. Pharmacy professionals should familiarise themselves with their local MRSA policy and alert system so that they can identify patients that require prompt decolonisation or review of their antibiotic treatment.