This document discusses Methicillin Resistant Staphylococcus aureus (MRSA). It begins by describing the characteristics of Staphylococcus including that it is a gram-positive coccus that can cause a variety of infections in humans. It then discusses the evolution of antibiotic resistance in S. aureus from penicillin to methicillin to vancomycin. It also covers the differences between hospital-acquired MRSA versus community-acquired MRSA and risks for infection. Treatment options for skin infections caused by MRSA are also summarized.

1. Methicillin Resistant
Staphylococcus Aureus
Peter Daley MD FRCPC DTM+H
Memorial University

3. Staphylococcus
Figure 19.1

4. Staphylococci
• Gram-positive cocci, nonmotile, facultative
anaerobes
• Cells occur in grapelike clusters because cells
division occurs along different planes and the
daughter cells remain attached to one another
• Salt-tolerant – allows them to tolerate the salt
present on human skin
• Tolerant of desiccation – allows survival on
environmental surfaces (fomites)

5. • Two species are commonly associated with
staphylococcal diseases in humans
– Staphylococcus aureus – the more virulent strain
that can produce a variety of conditions depending
on the site of infection
– Staphylococcus epidermidis – normal microbiota of
human skin that can cause opportunistic infections
in immunocompromised patients or when
introduced into the body

6. Pathogenicity
• “Staph’ infections result when staphylococci
breach the body’s physical barriers
• Entry of only a few hundred bacteria can result
in disease
• Pathogenicity results from three features
– Structures that enable it to evade phagocytosis
– Production of enzymes
– Production of toxins

7. Staphylococcus aureus in wound swab

8. Impetigo
• Superficial, local
• Pustular/crusted
• GAS/SA
• Children
• Topical therapy

9. Folliculitis
• Follicle infection
• SA
• Apocrine regions
• Whirlpool folliculitis
• May scar
• Acne
• Local treatment

10. Erysipelas
• GAS
• Portal of entry
• Lymphatic
involvement
• Bright red, painful
• Raised border
• Oral or IV therapy

11. Cellulitis
• Systemic illness
• Vague border
• GAS/SA
• Portal of entry
• Returns
• Occasional Vibrio,
Erysipelothrix
• Oral/IV therapy
• Edema control

12. Skin Abscess
• Furuncle, carbuncle
• Deep collection
• SA
• Needs drainage
• IVDU
• May be recurrent

14. Fournier’s Gangrene post-op

15. Evolution of Resistance in S. aureus
Penicillin Methicillin
Penicillin-resistant Methicillin-
S. aureus resistant
[1950s] S. aureus [1970s]
S. aureus (MRSA)
Vancomycin
[1997]
[1990s]
Vancomycin Vancomycin Vancomycin-resistant
resistant [ 2002 ] intermediate- enterococci (VRE)
S. aureus resistant
S. aureus
(VISA)

16. Mechanism of Methicillin Resistance
• Mediated by mecA gene
– Encodes abnormal low-affinity binding protein,
PBP-2a
– Encodes resistance to all beta-lactams
– MecA gene is located on a mobile genetic element
called SCCmec staphylococcal chromasomal
cassette
– That cassette may contain many other
resistance genes

17. HA-MRSA in Hospitals in
CANADA vs. U.S. (CNISP)
US Canada
50
% Resistant
40
30
20
10
0
83
87
92
94
96
98
00
19
19
19
19
19
19
20
Year
(Conly J. CMAJ 2002;167:885-891)

18. Many are colonized, few are infected
Clinical
Infections
Colonized
(Asymptomatic)
Patients

19. MRSA Surveillance Definitions
• Colonization – asymptomatic
• Infection – symptomatic
• Hospital acquired
• Healthcare associated – clinics, long term care
• Community acquired

20. S. aureus Colonization
• About 30% of people are colonized
• Average 2.8 strains /person
• Colonization more frequent in
– Newborns
– Hemodialysis patients
– People with dermatitis, eczema
– Diabetics
• Half Life: 40 months

21. CNISP 2009

22. CNISP 2009

23. CNISP 2009

24. CNISP 2009

25. CNISP 2009

26. Risk Factors for HA-MRSA
• Hospitalized within the last year
• Surgery within the last year
• Dialysis within last year
• Resided in long-term care facility
• ABX >3 times w/in past year
• DM

27. Were Hospital acquired MRSA so successful
only because they were antibiotic
resistant?
• Probably:
– Virulent but not hyper-virulent
– They are frequent colonizers but cause a respectable
number of infections.
– Patients with HA-MRSA often have more co-
morbidities and hence have higher mortality rates.
– We have to use less effective antibiotics
– Sometimes our initial guesses are wrong so patients
go untreated for several days

28. Community-Associated Methicillin-Resistant
S. aureus (CA-MRSA)
• First described in Australia in 1993
• In the late 1990s more reports of MRSA occurring in
the community in patients without established risk
factors (Usually skin infections)
– Younger patients
– Aboriginals especially in Sask and Manitoba
– Outbreaks:
• Injection drug users
• Players of contact sports
• Prison inmates
• Group homes

29. The emergence of CA-MRSA in
the United States
Methicillin-Resistant S. aureus Infections among
Patients in the Emergency Department Moran et
al
Volume 355:666-674, 2006

30. Prevalence of MRSA Among
422 ED Patients With SSTI
7/13 (54%) 11/28 (39%)
4/20 (20%)
59% 32/58 (55%)
43/58 (74%)
24/47 (51%) 17/25 (68%)
26/42 (62%)
23/32 (72%)
18/30 (60%)
46/69 (67%)
MSSA 17%
Moran GJ et al.

31. SSTIs in 11 US EDs,
August 2004
• 422 patients total Site of Infection:
• 62% male • Head/Neck 13%
• Median age 40
(range 18-79) • Torso 17%
• Racial mix: • Upper Ext 28%
White 28% • Lower Ext 28%
Black 46%
Hispanic 22% • Perineum 15%
Other 3%
Moran GJ et al. Society of Academic Emergency Medicine, 2005.

32. 185 cases from 1999-2002

33. CA-MRSA in athletes

34. A Clone of Methicillin-Resistant Staphylococcus aureus
among Professional Football Players
Kazakova SV, Hageman J, Matava M, et al.
N Engl J Med 2005; 352 (5): 468-75
• September 2003
• Large skin MRSA abscesses among St. Louis
Rams football team
• Subsequent cases in opposing team members
prompted
• November 2003
• CDC invited to investigate transmission (August 1-
November 30)

35. Results
• Attack rate: 5 out of 58 – 9%
• At sites of skin abrasions (turf burns)
on elbows, forearms, knees –
unprotected skin
• Large abscesses (5-7 cm) – I&D;
most infections lasted 10 days after
treatment; no hospitalization; total
17 days off field

36. Case Player Position

37. Results
• Skin abrasions common
• 2-3 turf burns/week from sliding on the field
• More frequent/more severe on artificial turf
• Trainers who provided wound care
• No regular access to hand hygiene
• Towels frequently shared
• 3 players/towel
• No showers before using communal whirlpool
• Equipment not routinely cleaned/ manufacturer
guidelines for cleaning whirlpools/saunas/steam
rooms not found.

39. MRSA as a community and hospital
pathogen
CA-MRSA HA-MRSA
Invasive/high rate of High rate of colonisation
infection
High %age of soft tissue Less likely to cause soft
infections tissue infection
Susceptible to non-beta- Multi-resistant
lactams (to date)
Causes necrotising infection Bacteremias, pneumonia
and wound infections

40. Panton-Valentine leucocidin (PVL) toxin
• Cytotoxin present in <5% of MSSA
• Rare in HA-MRSA
• Carried on bacteriophage …incorporated
into chromosome
• Capable of destroying WBC /severe tissue
damage and associated with necrotic skin
lesions /severe necrotizing pneumonia
Lina et al, CID: 29:1128, 1999

41. How to treat CA-MRSA SSTIs
• Culture • Antibiotics
– Severe skin infections – TMP/SMX
– All treatment failures of – Doxycycline
presumed S.aureus skin – Levo, Moxi might be OK
infections
– Clindamycin (if D-tested)
• Drainage is essential – No Macrolide or
Amoxicillin /clavulanic
acid

42. When to suspect CA-MRSA
• When CA-MRSA reaches 10-15% of strains, all
patients with SSTIs should be suspected.
• Severe Staph aureus infections, ie, necrotizing
fasciitis, necrotizing pneumonia, or neonatal
sepsis.
• When CA-MRSA risk factors are present.
• When there has been a poor response to
initial beta-lactam therapy.

43. Significance of S. aureus
Nasal Carriage
Nasal carriage of S. aureus is a risk for
infection in hospital (usually same strain):
– nosocomial bacteremia (RR 30; 95% CI 2.0-4.7) (von Eiff,
NEJM 2001; Wertheim, Lancet 2004)
– BSI, exit site infection in dialysis patients (Luzar, NEJM
1990; Kluytmans, ICHE 1996)
– SSI (2-9 X increased risk)
(Kluytmans, JID 1995; Perl, NEJM 2002; Kalmeijer, CID 2002)
– ICU-acquired infection (2-5 X increased risk) (Honda, ICHE
2010)

44. Significance of MRSA Colonization
Colonization with MRSA associated with a greater risk
of subsequent infection:
• Nasal carriers of MRSA 3.9 times more likely to develop
nosocomial staphylococcal bacteremia than were
MSSA carriers (Pujol, Am J Med 1996)
• MRSA colonization at ICU admission associated with
higher risk of ICU-acquired S. aureus (MRSA) infection; RR
4.1 (Honda, Infect Control Hosp Epidemiol 2010)

45. Risk of MRSA Colonization Becoming
an Infection
• 60 of 209 (29%) adults with newly identified
colonization developed a subsequent MRSA
infection during 18 months of follow-up (Huang, CID
2003)
• 8 of 38 (21%) with newly identified colonization
developed MRSA infection in 1 year of follow-up
(Davis, CID 2004)

46. Decolonization
• Decolonization is not recommended for usual
management.
• Decolonization may be tried when patients have
multiple infections over several months.
• The recommended regimen is mupirocin ointment
bid for 10 days.
• Mupirocin susceptibility should be tested.
• “A combined strategy of intranasal mupirocin topical
antiseptics and systemic antibiotics, eg. rifampin or
clindamycin may be considered.”

47. S. aureus Decolonization
Recommendations
• possibly useful in patients with recurrent skin/soft
tissue infection (need more data for CA-MRSA)
• mupirocin susceptibility testing should be done prior
to use for decolonization
• MRSA as an infection control measure needs to be
studied; consider in outbreaks or select patients

48. S. aureus Decolonization
Recommendations
• no routine decolonization pre-op or in
nonsurgical patients; perhaps consider in
surgical patients known to be S. aureus
carriers
• consider in dialysis patients, but risk of
mupirocin resistance in the long-term

49. Environmental contamination of surfaces in an
MRSA patient room
Resistant bacteria on the skin or in the gastrointestinal tract of patients
can often be found on common items.
Bed Linen
Patient Gown
Overbed Table
BP Cuff
Side Rails
Bath Door Handle
IV Pump Button
Room Door Handle
0 10 20 30 40 50 60
Percent of Surfaces Contaminated

50. Manorapid
Synergy
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Antiseptica
Remember!!