Methicillin-resistant Staphylococcus aureus

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Methicillin-resistant Staphylococcus aureus (MRSA) is a specific strain of the Staphylococcus aureus bacterium that has developed antibiotic resistance to all penicillins, including methicillin and other narrow-spectrum β-lactamase-resistant penicillin antibiotics.^[1] MRSA was first discovered in the UK in 1961 and is now widespread, particularly in the hospital setting where it is commonly termed a superbug.

MRSA may also be known as oxacillin-resistant Staphylococcus aureus (ORSA) and multiple-resistant Staphylococcus aureus, while non-methicillin resistant strains of S. aureus are sometimes called methicillin-susceptible Staphylococcus aureus (MSSA) if an explicit distinction must be made.

Although MRSA has traditionally been seen as a hospital-associated infection, there is currently an epidemic of community-acquired MRSA in the USA. The abbreviations CA-MRSA (community-associated MRSA) and HA-MRSA (hospital-associated MRSA) are now commonly seen in the literature.

Contents 1 Introduction 2 Microbiology 3 Mortality 4 Clinical presentation and concerns 5 Treatment 6 Prevention and infection control 7 Epidemiology 7.1 Strains 8 References 9 External links

[edit] Introduction

Staphylococcus bacteria are extremely common in the environment (and a third of humans world-wide are estimated to carry it on their bodies and are not harmed by it), and is usually not a problem to healthy individuals. Historically, staph infections begin only after the individual has suffered a skin break or open wound. Recently, due to institutional overuse of antibiotics, strains of staphylococcus aureus have developed drug resistance. If an individual has a weak immune response to the bacteria, a MRSA infection can result even with no apparent open wound. The symptoms can range from skin boils to necrotizing fasciitis, popularly known as flesh-eating disease. MRSA infections are typically combatted with vancomycin, however, vancomycin-resistant staphylococcus has recently appeared.

Interestingly, MRSA cases chiefly emanate from institutions such as hospitals and gymnasiums. Many professional athletes have developed MRSA infections from exposure in stadium locker rooms. On June 22, 2006, the U.S. Centers for Disease Control and Prevention issued an alert regarding an outbreak in tattoo parlors [1], after 54 customers developed MRSA from unlicensed tattoo artists.

[edit] Microbiology

Methicillin resistance arises by acquisition of a staphylococcal cassette chromosome SCCmec, and is conferred by the mecA gene. Expression of this gene yields PBP2a, a penicillin binding protein with reduced affinity for β-lactam rings (the primary active-site of the β-lactam antibiotics).^[2]

Some strains of S. aureus over-express β-lactamase and appear to be resistant to oxacillin and, rarely, methicillin despite being mecA-negative. They have slightly raised minimum inhibitory concentrations (MICs) and may thus be described as "minimally resistant". Other strains express modified PBPs (not PBP2) and exhibit varying degrees of β-lactam antibiotic resistance.

[edit] Mortality

Although Noskin and others report that a patient infected with MRSA is five times more likely to die than other patients;[2] it is not clear that patients who are infected with MRSA have an increased death rate. Wyllie et al. report a death rate of 34 percent within 30 days among patients infected with MRSA, while among MSSA patients the death rate was similar at 27%.^[3]

[edit] Clinical presentation and concerns

S. aureus most commonly colonises the anterior nares (the nostrils) although the respiratory tract, open wounds, intravenous catheters and urinary tract are also potential sites for infection.

MRSA infections are usually asymptomatic in healthy individuals and may last from a few weeks to many years. Patients with compromised immune systems are at significantly greater risk of a symptomatic secondary infection.

According to Betsy McCaughey, founder of the Committee to Reduce Infection Deaths, MRSA can be detected in asymptomatic patients by a blood test. Combined with extra sanitary measures for those in contact with infected patients, screening patients admitted to hospitals has been found effective in minimizing spread of MRSA in hospitals in Denmark, Finland and the Netherlands. In the United States the Centers for Disease Control and Prevention, in guidelines issued 19 October, 2006, citing the need for additional research, declined to recommend such screening. ^{[4] [5]}

[edit] Treatment

Vancomycin and teicoplanin are glycopeptide antibiotics used to treat MRSA infections. Teicoplanin is a structural congener of vancomycin that has a similar activity spectrum but a longer half-life (t½). Both drugs have low oral absorption thus are administered intravenously for systemic infections, with the exception of pseudomembranous colitis where vancomycin can be given by mouth for this GI tract infection.

Several new strains of MRSA have been found showing antibiotic resistance even to vancomycin and teicoplanin; those new evolutions of the MRSA bacteria are dubbed vancomycin intermediate-resistant Staphylococcus aureus (VISA).^[6] Linezolid, quinupristin/dalfopristin, daptomycin, tigecycline are more recent additions to the therapeutic arsenal, generally reserved for severe infections which do not respond to glycopeptides. Less severe infections may be treated by oral agents including: linezolid, rifampicin+fusidic acid, pristinamycin, co-trimoxazole (trimethoprim+sulfamethoxazole), doxycycline, and clindamycin.

On May 18, 2006 a team of researchers from Merck Pharmaceuticals published in Nature that they had discovered an entirely new type of antibiotic, called platensimycin, and have demonstrated that it can be used successfully to fight MRSA.[3]

[edit] Prevention and infection control

Alcohol had been proven to be an effective sanitizer against MRSA. Quaternary ammonium can be used in conjunction with alcohol to increase the duration of the sanitizing action. The prevention of nosocomial infections involve routine and terminal cleaning. Nonflammable Alcohol Vapor in CO₂ (NAV-CO2) systems or sodium hypochlorite are frequently used to sanitize rooms occupied by patients infected or colonized with MRSA.

At the end of August 2004, after a successful pilot scheme to tackle MRSA, the UK National Health Service announced its Clean Your Hands campaign. Wards will be required to ensure that alcohol-based hand rubs are placed near to all beds so that staff can hand wash more regularly. It is thought that if this cuts infection by just 1% the plan will pay for itself many times over. Health care workers in the United States are reportedly largely neglecting the simple-yet-effective practice of hand-washing^{[citation needed]}, despite the Centers for Disease Control and Prevention (CDC)'s report that hand-washing alone would save the lives of roughly 30,000 patients per year, not from MRSA alone, but from all nosocomial infections.

Mathematical models describe one way in which a loss of infection control can occur after measures for screening and isolation seem to be effective for years, as happened in the UK. In the "search and destroy" strategy that was employed by all UK hospitals until the mid 1990's, all patients with MRSA were immediately isolated, and all staff were screened for MRSA and were prevented from working until they had completed a course of eradication therapy that was proven to work. Loss of control occurs because colonised patients are discharged back into the community and then readmitted: when the number of colonised patients in the community reaches a certain threshold, the "search and destroy" strategy is overwhelmed.^[7] One of the few countries not to have been overwhelmed by MRSA is the Netherlands: an important part of the success of the Dutch strategy may have been to attempt eradication of carriage upon discharge from hospital.^[8] For countries that have been overwhelmed by MRSA (such as the US and UK), the Dutch model suggests that a co-ordinated re-instatement of search and destroy measures can still bring MRSA under control,^[8] but given the enormous investment in facilites that would be required others have suggested that for all practical purposes the point of no return has already been passed.^[9]

[edit] Epidemiology

Up to 53 million people are thought to carry MRSA. Scientists estimate that around 2 billion people, some 25-30 percent of the world's population, have a form of the staph bacteria. [4] [5]

Because cystic fibrosis patients are often treated with multiple antibiotics in hospital settings, they are often colonised with MRSA, potentially increasing the rate of life-threatening MRSA pneumonia in this group. The risk of cross-colonisation has led to increased use of isolation protocols among these patients. In a hospital setting, patients who have received fluoroquinolones are more likely to become colonised with MRSA,^[10] this is probably because many circulating strains of MRSA are fluoroquinolone-resistant, which means that MRSA is able to colonise patients whose normal skin flora have been cleared of non-resistant Staph. aureus by fluoroquinolones.

In the US there are increasing reports of outbreaks of MRSA colonisation and infection through skin contact in locker rooms and gymnasiums, even among healthy populations. MRSA also is becoming a problem in paediatrics, [6] including hospital nurseries.[7]

MRSA causes as many as 20% of Staphylococcus aureus infections in populations that use intravenous drugs. These out-of-hospital strains of MRSA, now designated as community-acquired, methicillin-resistant staph. aureus, or CA-MRSA, are not only difficult to treat but are especially virulent. CA-MRSA apparently did not evolve de novo in the community, but represents a hybrid between MRSA which escaped from the hospital environment and the once easily treatable community organisms. Most of the hybrid strains also acquired a virulence factor which makes their infections invade more aggressively, resulting in deep tissue infections following minor scrapes and cuts, and many cases of fatal pneumonia as well.[8]

As of early 2005, the number of deaths in the United Kingdom attributed to MRSA has been estimated by various sources to lie in the area of 3000 per year.^[11] The staphylococcus bacteria accounts for almost half of all UK hospital infections. The issue of MRSA infections in hospitals has recently been a major political issue in the UK, playing a significant role in the debates over health policy in the general election held in that country in 2005.

During the summer of 2005, researchers in The Netherlands discovered that three pig farmers or their families were infected by MRSA bacteria that were also found on their pigs.^[12] Researchers from Radboud University Nijmegen are now investigating how widespread the MRSA bacteria is in pigs, and whether it will become characterised among the zoonoses.

Recently, it has been observed that MRSA can replicate inside of Acanthamoeba, increasing MRSA numbers 1000-fold [9]. Since Acanthamoeba can form cysts easily picked up by air currents, these organisms can spread MRSA via airborne routes. Whether control of Acanthamoeba in the clinical environment will also help to control MRSA, remains an area for research.

[edit] Strains

In the UK, the most common strains are EMRSA15 and EMRSA16.^[13] EMRSA16 is the best described epidemiologically and originated in Kettering.

In the USA, the epidemic of community-associated MRSA is due to a CC8 strain designated ST8:USA300, which carries mec type IV, Panton-Valentine leukocidin, and enterotoxin Q and K.^[14] Other community-associated strains of MRSA are ST8:USA500 and ST59:USA1000.

The most common epidemic hospital-associated MRSA in the USA is a CC30 strain, ST36:USA200, which carries the SCCmec type II, enterotoxin A and toxic shock syndrome toxin 1 genes.^[14]

[edit] References

1. ^ Foster T (1996). Staphylococcus. In: Barron's Medical Microbiology (Barron S et al, eds.), 4th ed., Univ of Texas Medical Branch. (via NCBI Bookshelf) ISBN 0-9631172-1-1.
2. ^ Guignard B, Entenza JM, Moreillon P (2005). "Beta-lactams against methicillin-resistant Staphylococcus aureus". Curr Opin Pharmacol 5 (5): 479-89. PMID 16095969.
3. ^ Wyllie DH, Crook DW, Peto TEA (2006). "Mortality after Staphylococcus aureus bacteraemia in two acute hospitals in Oxfordshire, 1997–2003: cohort study". Brit Med J 333: 281–4.
4. ^ "To Catch a Deadly Germ", New York Times opinion
5. ^ CDC Guideline "Management of Multidrug-Resistant Organisms in Healthcare Settings, 2006"
6. ^ Schito GC (2006). "The importance of the development of antibiotic resistance in Staphylococcus aureus". Clin Microbiol Infect 12 Suppl 1: 3-8. PubMed.
7. ^ Cooper BS, Medley GF, Stone SP, et al. (2004). "Methicillin-resistant Staphylococcus aureus in hospitals and the community: stealth dynamics and control catastrophes". Proc Natl Acad Sci USA 101 (27): 10223–8. PMID 15220470.
8. ^ ^{a b} Bootsma MC, Diekmann O, Bonten MJ (2006). "Controlling methicillin-resistant Staphylococcus aureus: quantifying the effects of interventions and rapid diagnostic testing". Proc Natl Acad Sci USA 103 (14): 5620–5. PMID 16565219.
9. ^ Paul J (2006). "Surveillance and management of all types of Staphylococcus aureus bacteraemia: MRSA policies divert attention from MSSA and may risk lives". Brit Med J 333 (7562): 269–70.
10. ^ Charbonneau P, Parienti J-J, Thibon P, et al. (2006). "Fluoroquinolone use and Methicillin-resistant Staphylococcus aureus isolations rates in hospitalized patients: a quasi experimental study". Clin Infect Dis 42: 778–84.
11. ^ Johnson AP, Pearson A, Duckworth G (2005). "Surveillance and epidemiology of MRSA bacteraemia in the UK". J Antimicrob Chemother 56 (3): 455-62. PMID 16046464.
12. ^ Voss A, Loeffen F, Bakker J, Klaassen C, Wulf M (2005). "Methicillin-resistant Staphylococcus aureus in pig farming". Emerg Infect Dis 11 (12): 1965-6. PubMed fulltext.
13. ^ Johnson AP, Aucken HM, Cavendish S, Ganner M, Wale MC, Warner M, Livermore DM, Cookson BD (2001). "Dominance of EMRSA-15 and -16 among MRSA causing nosocomial bacteraemia in the UK: analysis of isolates from the European Antimicrobial Resistance Surveillance System (EARSS)". J Antimicrob Chemother 48 (1): 143-4. PMID 11418528 Full correspondence.
14. ^ ^{a b} Diep BA, Carleton HA, Chang RF, et al. (2006). "Roles of 34 virulence genes in the evolution of hospital- and community-associated strains of methicillin-resistant Staphylococcus aureus". J Infect Dis 193 (11): 1495–1503.

[edit] External links

• Susceptibility of methicillin-resistant Staphylococcus aureus to the essential oil of Melaleuca alternifolia
• The effect of essential oils on methicillin-resistant Staphylococcus aureus
• Support for patients with MRSA and their caregivers
• CDC article on MRSA
• Step up the superbug battle, CDC tells hospitals
• CDC Guideline "Management of Multidrug-Resistant Organisms in Healthcare Settings, 2006"