'Methicillin-resistant '' Staphylococcus aureus''' ('MRSA') is an isolate of the
bacterium ''
Staphylococcus aureus'' that has acquired genes encoding
antibiotic resistance to all
penicillins, including
methicillin and other narrow-spectrum
β-lactamase-resistant penicillin
antibiotics.
[1] MRSA was discovered for the first time in 1961 in the
UK, but it is now widespread in the hospital setting. MRSA is commonly termed a
superbug.
MRSA may also be known as 'oxacillin-resistant ''Staphylococcus aureus'' (ORSA)' and 'multiple-resistant ''Staphylococcus aureus'''. Strains of ''S. aureus'' that are non-resistant to methicillin 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, community-acquired MRSA strains have appeared in recent years, notably in the
U.S. and
Australia.
[2] The abbreviations 'CA-MRSA' (community-associated MRSA) and 'HA-MRSA' (hospital-associated MRSA) are now commonly seen in medical literature.
Microbiology
''Staphylococcus aureus'' became methicillin resistant by acquiring a ''
mecA''
gene, usually carried on a larger piece of DNA called a staphylococcal cassette chromosome ''
SCCmec''. Expression of mecA yields PBP2a, a
penicillin binding protein with reduced affinity for β-lactam antibiotic binding.
[3] Penicillin binding proteins are necessary for correct synthesis of the bacterial cell wall, and when they are blocked by penicillin, the cell wall is incorrectly formed, and the cell is liable to lyse. PBP2a allows the bacterium to synthesise cell wall normally in the presence of methicillin.
Some strains of ''S. aureus'' over-express
β-lactamase and thus can appear to be resistant to
oxacillin and, rarely, methicillin despite being ''mecA''-negative. Beta-lactamase is an enzyme that cleaves the penicillin molecule at its cyclic ring, and second generation penicillins like methicillin were specifically designed to resist beta-lactamase activity.
Recent outbreaks of CA-MRSA appear to be caused by isolates that also carry genes for
Panton-Valentine leukocidin (PVL),
[ Necrotizing fasciitis caused by community-associated methicillin-resistant ''Staphylococcus aureus'' in Los Angeles, Miller L, Perdreau-Remington F, Rieg G, Mehdi S, Perlroth J, Bayer A, Tang A, Phung T, Spellberg B, , , N Engl J Med, 2005 ] a toxin that is known to cause lysis of white blood cells. It has been shown that PVL contributes to severe haemolytic and necrotic pneumonia in children,
[4] but its role in severe skin and soft tissue infection is currently debated.
[5]
Morbidity and mortality
It has been difficult to quantify the degree of morbidity and mortality attributable to MRSA. Patients with ''S. aureus'' infection had, on average, 3 times the length of hospital stay (14.3 vs 4.5 days), 3 times the total charges ($48,824 vs $14,141), and 5 times the risk of in-hospital death (11.2% vs 2.3%) than inpatients without this infection.
[6] Cosgrove ''et al'',
[7] in a meta-analysis of 31 studies, conclude that bacteremia as a result of MRSA is associated with an increased mortality compared with MSSA bacteraemia with an odds ratio of 1.93 (95% CI,
1.54±2.42; P
[8] In addition, Wyllie ''et al.'' report a death rate of 34% within 30 days among patients infected with MRSA, while among MSSA patients the death rate was similar at 27%.
[9]
The major issue is that there are a number of factors that can lead to someone's death, and it is believed that patients with MRSA bacteraemia are sicker and will consequently have a higher mortality because of their underlying illness. However, several studies including one by Blot and colleagues that have adjusted for underlying disease still found MRSA bacteraemia to have a higher attributable mortality than MSSA bacteraemia.
[10]
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.
[11]
Many people who are symptomatic present with pus-filled boils, and occasionally with rashes.
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.
[12][13]
Treatment
Community-acquired MRSA often results in abscess formation that requires incision and drainage to treat. Prior to ca-MRSA, abscesses were not considered contagious (it was assumed that violation of skin integrity with introduction of staph from normal skin colonization was required). However, newly emerging ca-MRSA is transmissable (similar, but with very important differences) from hospital-acquired MRSA. ca-MRSA is less likely to cause cellulitis than other forms of MRSA.
Vancomycin and
teicoplanin are glycopeptide antibiotics used to treat MRSA infections.
[14] Teicoplanin is a structural
congener of vancomycin that has a similar activity spectrum, but a longer
half-life (t½).
[15] The oral absorption of vancomycin and teicoplanin is very low and must be administered intravenously in order to control systematic infections.
[16] One of the problems with vancomycin is not just that its route of administration is inconvenient, but also that it is inferior in terms of its efficacy compared to
antistaphylococcal penicillins.
[17][18]
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).
[19][20] Linezolid,
quinupristin/dalfopristin,
daptomycin,
tigecycline are used to treat more severe infections that do not respond to the glycopeptides such as vancomycin.
[21] MRSA infections can be treated with oral agents such as
linezolid,
rifampicin+
fusidic acid,
rifampicin+
fluoroquinolone,
pristinamycin,
co-trimoxazole (trimethoprim-sulfamethoxazole),
doxycycline or
minocycline, and
clindamycin.
[22]
On
18 May 2006, a team of researchers from
Merck Pharmaceuticals published in ''Nature'' that they had discovered an entirely new type of antibiotic, called
platensimycin, and they have demonstrated that it can be used successfully to fight MRSA.
[23][24]
An entirely different and promising approach is
phage therapy (e.g., at the
Tbilisi Institute in
Georgia), which reports efficacy against up to 95% of tested ''Staphylococcus'' isolates.
[25]
Raw honey dressings are also being successfully used for prevention and treatment of MRSA.
[26][27]
It has been reported that
use of maggots to treat an MRSA infection has been successful. Studies have been done on diabetic patients and the treatment time has been significantly less than that of other standard treatments.
[28] [29]
Prevention and infection control strategies
Alcohol has proven to be an effective topical 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 have an advantage as they do not attack metals or plastics used in medical environments, and do not contribute to antibacterial resistance.
As MRSA has the capability to survive on surfaces and fabrics including privacy curtains or garments worn by care providers, the need for complete surface sanitation is necessary to eliminate MRSA in areas where patients are recovering from invasive procedures. Vaporized sanitizers reach areas missed by traditional cleaning methods, particularly in ICU and ER units. Ambulances, police vehicles, artificial turf surfaces, and sports equipment are also areas where MRSA can be found.
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 are reportedly largely neglecting the simple, yet effective, practice of hand-washing, 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 in the US, 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
1990s, 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.
[30] 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.
[31] However, the number of MRSA infected people in the Netherlands is currently rising, because of numerous infections in pig farms. The MRSA strain is carried from pig to human. Very recently, the Dutch food association has discovered strains of the MRSA bacterium on pork meat. These strains were able to infect humans. For countries that have been overwhelmed by MRSA (such as the U.S. and UK), the Dutch model suggests that a co-ordinated re-instatement of search and destroy measures can still bring MRSA under control,
31 but given the enormous investment in facilities that would be required others have suggested that for all practical purposes the point of no return has already been passed.
[32]
Epidemiology
Worldwide, an estimated 2 billion people carry some form of ''S. aureus''; of these, up to 53 million (2.7% of carriers) are thought to carry MRSA.
[33] In the United States, 95 million carry ''S. aureus'' in their noses; of these 2.5 million (2.6% of carriers) carry MRSA.
[34] A population review conducted in 3 communities in the US showed the annual incidence of CA-MRSA during 2001–2002 to be 18–25.7/100,000 ; most CA-MRSA isolates were associated with clinically relevant infections, and 23% of patients required hospitalization.
[35]
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,
[36] 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 ''S. aureus'' by fluoroquinolones.
In the USA, reports have been increasing 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,
[37] including hospital nurseries.
[38] A 2007 study found that 4.6% of patients in US healthcare facilities were infected or colonized with MRSA.
[39]
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 ''Staphylococcus aureus'', or CA-MRSA, are more easily treated than hospital-acquired MRSA (although more virulent than MSSA). 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.
[40]
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.
[41] ''Staphylococcus'' bacteria account 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
United Kingdom general election held 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.
[42] 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.
[43] 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.
Strains
In the UK, the most common strains are EMRSA15 and EMRSA16.
[44] EMRSA16 is the best described epidemiologically: it originated in
Kettering, England, and the full genomic sequence of this strain has been published.
[45] This has been recognised as being identical to the
ST36:USA200 strain which circulates in the USA, and carries the SCC''mec'' type II,
enterotoxin A and
toxic shock syndrome toxin 1 genes.
47 Under the new international typing system, this strain is now called MRSA252 and the entire genome sequence of this strain has been published. It is not entirely certain why this strain has become so successful, whereas previous strains have failed to persist: one explanation is the characteristic pattern of antibiotic sensitivities. Both the EMRSA-15 and -16 strains are resistant to
erythromycin and
ciprofloxacin: It is known that ''Staphylococcus aureus'' can survive intracellularly,
[46] and these are precisely the antibiotics that best penetrate intracellularly: it may be that these strains of ''S. aureus'' are therefore able to exploit an intracellular niche.
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
enterotoxins Q and K.
[47] Other community-associated strains of MRSA are ST8:USA500 and ST59:USA1000.
See also
★
Drug resistance
★ Drug resistant diseases
★
★
VRSA
★
★
MDR-TB
★
★
XDR-TB
★
★
VRE
★
★
CDF
References
1. ''Staphylococcus''. ''In:'' Barron's Medical Microbiology ''(Barron S ''et al'', eds.), Foster T, , , Univ of Texas Medical Branch, 1996, ISBN 0-9631172-1-1
2. Dissemination of new methicillin-resistant ''Staphylococcus aureus'' clones in the community, Okuma K, Iwakawa K, Turnidge J, ''et al'', , , J Clin Microbiol, 2002
3. Beta-lactams against methicillin-resistant ''Staphylococcus aureus'', Guignard B, Entenza JM, Moreillon P, , , Curr Opin Pharmacol, 2005
4. ''Staphylococcus aureus'' Panton-Valentine leukocidin causes necrotizing pneumonia., Labandeira-Rey M, Couzon F, Boisset S, Brown EL, Bes M, Benito Y, Barbu EM, Vazquez V, Hook M, Etienne J, Vandenesch F, Bowden MG., , , Science, 2007
5. Is Panton-Valentine leukocidin the major virulence determinant in community-associated methicillin-resistant ''Staphylococcus aureus'' disease?, Voyich JM, Otto M, Mathema B, Braughton KR, Whitney AR, Welty D, Long RD, Dorward DW, Gardner DJ, Lina G, Kreiswirth BN, DeLeo FR, , , J Infect Dis, 2006
6. The Burden of ''Staphylococcus aureus'' Infections on Hospitals in the United States: An Analysis of the 2000 and 2001 Nationwide Inpatient Sample Database, Noskin GA, Rubin RJ,Schentag JJ, Kluytmans J, Hedblom EC, Smulders M, Lapetina E, Gemmen E, , , Arch Intern Med, 2005
7. The impact of Methicillin Resistance in ''Staphylococcus aureus'' Bacteremia on Patient Outcomes: Mortality, Length of Stay, and Hospital Charges, Cosgrove SE, Qi Y, Kaye KS, Harbarth S, Karchmer AW, Carmeli Y, , , Infection Control and Hospital Epidemiology, 2005
8. Methicillin resistant ''Staphylococcus aureus'' in the critically ill, Hardy KJ, Hawkey PM, Gao F, Oppenheim BA, , , British Journal of Anaesthesia, 2004
9. Mortality after ''Staphylococcus aureus'' bacteraemia in two hospitals in Oxfordshire, 1997-2003: cohort study, Wyllie D, Crook D, Peto T, , , BMJ, 2006
10. Outcome and attributable mortality in critically Ill patients with bacteremia involving methicillin-susceptible and methicillin-resistant ''Staphylococcus aureus'', Blot S, Vandewoude K, Hoste E, Colardyn F, , , Arch Intern Med, 2002
11.
12. "To Catch a Deadly Germ", ''New York Times'' opinion
13. CDC Guideline "Management of Multidrug-Resistant Organisms in Healthcare Settings, 2006"
14. Genesis of methicillin-resistant ''Staphylococcus aureus'' (MRSA), how treatment of MRSA infections has selected for vancomycin-resistant Enterococcus faecium, and the importance of antibiotic management and infection control, Schentag JJ, Hyatt JM, Carr JR, Paladino JA, Birmingham MC, Zimmer GS, Cumbo TJ, , , Clin. Infect. Dis., 1998
15. Teicoplanin pharmacokinetics in intravenous drug abusers being treated for bacterial endocarditis, Rybak MJ, Lerner SA, Levine DP, Albrecht LM, McNeil PL, Thompson GA, Kenny MT, Yuh L, , , Antimicrob. Agents Chemother., 1991
16. The treatment of staphylococcal infections with special reference to pharmacokinetic, pharmacodynamic and pharmacoeconomic considerations, Janknegt R, , , Pharmacy world & science : PWS, 1997
17. ''Staphylococcus aureus'' bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study., Chang FY, Peacock JE Jr, Musher DM, ''et al.'', , , Medicine (Baltimore), 2003
18. The role of vancomycin in the persistence or recurrence of ''Staphylococcus aureus'' bacteraemia, Siegman-Igra Y, Reich P, Orni-Wasserlauf R, Schwartz D, Giladi M., , , Scand J Infect Dis, 2005
19. Inhibition of cell wall turnover and autolysis by vancomycin in a highly vancomycin-resistant mutant of ''Staphylococcus aureus'', Sieradzki K, Tomasz A, , , J. Bacteriol., 1997
20. {{cite journal | author=Schito GC | title=The importance of the development of antibiotic resistance in ''Staphylococcus aureus'' | journal=Clin Microbiol Infect | year=2006 | pages=3-8 | volume=12 Suppl 1 | pmid = 16445718} }}
21. Severe ''Staphylococcus aureus'' infections caused by clonally related community-acquired methicillin-susceptible and methicillin-resistant isolates, Mongkolrattanothai K, Boyle S, Kahana MD, Daum RS, , , Clin. Infect. Dis., 2003
22. Linezolid for the treatment of multidrug-resistant, gram-positive infections: experience from a compassionate-use program, Birmingham MC, Rayner CR, Meagher AK, Flavin SM, Batts DH, Schentag JJ, , , Clin. Infect. Dis., 2003
23. Triclosan resistance in methicillin-resistant ''Staphylococcus aureus'' expressed as small colony variants: a novel mode of evasion of susceptibility to antiseptics, Bayston R, Ashraf W, Smith T, , , J. Antimicrob. Chemother., 2007
24. {{cite journal | author=Wang J | title=Platensimycin is a selective FabF inhibitor with potent antibiotic properties | journal=Nature | year=2006 | month = May | pages=358-361 | issue=441 | pmid = 16710421} }}
25. Experimental protection of mice against lethal ''Staphylococcus aureus'' infection by novel bacteriophage phi MR11, Matsuzaki S, Yasuda M, Nishikawa H, Kuroda M, Ujihara T, Shuin T, Shen Y, Jin Z, Fujimoto S, Nasimuzzaman MD, Wakiguchi H, Sugihara S, Sugiura T, Koda S, Muraoka A, Imai S, , , J. Infect. Dis., 2003
26. Harnessing honey's healing power
27. Honey as a topical antibacterial agent for treatment of infected wounds Molan C
28. Maggots help cure MRSA patients
29. Maggots rid patients of MRSA
30. Methicillin-resistant ''Staphylococcus aureus'' in hospitals and the community: stealth dynamics and control catastrophes, Cooper BS, Medley GF, Stone SP, ''et al.'', , , , 2004
31. Controlling methicillin-resistant ''Staphylococcus aureus'': quantifying the effects of interventions and rapid diagnostic testing, Bootsma MC, Diekmann O, Bonten MJ, , , Proc Natl Acad Sci USA, 2006
32. Surveillance and management of all types of ''Staphylococcus aureus'' bacteraemia, Paul J, , , BMJ, 2006
33. MRSA Infections - [keepkidshealthy.com]
34. A U.S. population-based survey of ''Staphylococcus aureus'' colonization, Graham P, Lin S, Larson E, , , Ann Intern Med, 2006
35.
36. Fluoroquinolone use and methicillin-resistant ''Staphylococcus aureus'' isolation rates in hospitalized patients: a quasi experimental study, Charbonneau P, Parienti J, Thibon P, Ramakers M, Daubin C, du Cheyron D, Lebouvier G, Le Coutour X, Leclercq R, , , Clin Infect Dis, 2006
37. MRSA: the problem reaches paediatrics - Archives of Disease in Childhood
38. Community-associated Methicillin-resistant ''Staphylococcus aureus'' in Hospital Nursery and Maternity Units - CDC
39.
National Prevalence Study of Methicillin-Resistant Staphylococcus aureus (MRSA) in U.S. Healthcare Facilities Association for Professionals in Infection Control & Epidemiology
40. Community-acquired meticillin-resistant Staphylococcusaureus: an emerging threat - The Lancet
41. Surveillance and epidemiology of MRSA bacteraemia in the UK, Johnson AP, Pearson A, Duckworth G, , , J Antimicrob Chemother, 2005
42. Methicillin-resistant ''Staphylococcus aureus'' in pig farming, Voss A, Loeffen F, Bakker J, Klaassen C, Wulf M, , , Emerg Infect Dis, 2005
43. Single Cell Amoeba Increases MRSA Numbers One Thousand Fold
44. 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), Johnson AP, Aucken HM, Cavendish S, ''et al.'', , , J Antimicrob Chemother, 2001
45. Complete genomes of two clinical ''Staphylococcus aureus'' strains: Evidence for the rapid evolution of virulence and drug resistance, Holden MTG, Feil EJ, Lindsay JA, ''et al.'', , , Proc Natl Acad Sci U S A, 2004
46. Intracellular persistence of ''Staphylococcus aureus'' small-colony variants within keratinocytes: a cause for antibiotic treatment failure in a patient with Darier's disease, von Eiff C, Becker K, Metze D, ''et al.'', , , Clin Infect Dis, 2001
47. Roles of 34 virulence genes in the evolution of hospital- and community-associated strains of methicillin-resistant ''Staphylococcus aureus'', Diep B, Carleton H, Chang R, Sensabaugh G, Perdreau-Remington F, , , J Infect Dis, 2006
Further reading
★
Susceptibility of methicillin-resistant ''Staphylococcus aureus'' to the essential oil of ''Melaleuca alternifolia'', Carson CF, Cookson BD, Farrelly HD, Riley TV, , , J. Antimicrob. Chemother., 1995
★
The effect of essential oils on methicillin-resistant ''Staphylococcus aureus'' using a dressing model, Edwards-Jones V, Buck R, Shawcross SG, Dawson MM, Dunn K, , , Burns : journal of the International Society for Burn Injuries, 2004
External links
★
CDC Article on Hospital Acquired MRSA
★
CDC Article on Community Acquired MRSA
★
CDC Guideline "Management of Multidrug-Resistant Organisms in Healthcare Settings, 2006"
★
The Independent - PVL: New strain of superbug targets the young, and its latest victim is an NHS nurse - 18/12/06
★
BURDEN of Resistance and Disease in European Nations - An EU-Project to estimate the financial burden of antibiotic resistance in European Hospitals
★
MRSA and Families Network an Irish support group for people and families that have been affected by MRSA and raising awareness of the infection. They have many branches of the network nationwide.
★
MRSA Action UK a charity that aims "to raise public awareness and to influence Government and healthcare providers in the fight to prevent MRSA and all healthcare associated infections"
★
Deadly Superbugs, a Reader's Digest article on Community Acquired MRSA
★
MRSA Watch provides an index of 4000 articles on MRSA covering every aspect of it's diagnosis and treatment."
★
Bacterial Infections Including MRSA Superbug
العربية
中国
Français
Deutsch
Ελληνική
हिन्दी
Italiano
日本語
Português
Русский
Español
