Community Acquired Methicillin- Resistant
Staphylococcus aureus
Mohamad Mooty, M.D.
Infectious Diseases
Eastern Maine Medical Center
MRSA Historical Aspects
1959
First clinical use of methicillin
1961
First description of MRSA
1967
First report of nosocomial infection in the US (2 cases)
1968
Increase in MRSA in the UK
1968-1979 Rise and subsequent wane of prevalence of MRSA
(especially nosocomial infections) in Europe, Australia,
and elsewhere (except US)
1975-1980 First reports of problems with MRSA in the US; most
occurred in large tertiary care hospitals (especially burn
units and ICUs)
1980
MRSA increase in prevalence in US nursing homes;
CA-MRSA infections in the US
1998
Emergence of CA-MRSA
•Public Health Agency of Canada (PHAC). Can Commun Dis Rep. 1997
• Wertheim HF, et al. J Hosp Infect. 2004
• Miller LG, et al. N Engl J Med. 2005
• Francis JS. Clin Infect Dis. 2005
• Gillet Y, et al. Lancet. 2002
• Lowry FD. N Engl J Med 1998
• US Centers for Disease Control and Prevention. Am J Infect Control. 1999
MRSA Historical Aspects
• USA Prevalence in ICU: 60 percent
• More than 90,000 invasive infections due to
MRSA occurred in the United States in 2005
CommunityAssociated
Heatlh-Care
Associated
Chloramphenicol
Usually Susceptible
Frequently Resistant
Clindamycin
Usually Susceptible
Frequently Resistant
Erythromycin
Usually Resistant
Usually Resistant
Geographic Variability
Usually Resistant
Usually Susceptible
Usually Susceptible
SCC mec type
IV
II
Lineage
USA 300, USA 400
USA 100, USA 200
Toxin-Producing
More
Fewer
PVL-Producing
Common
Rare
Health Care Exposure
Less frequent
More frequent
Characteristic
Susceptibility
Fluoroquinolones
TMP-SMX
Definition
History
Epidemiology
Clinical Features
Virulence Factors
Risk Factors
Clinical Management “Outpatient”
 Prevention “Decolonization”
Oxacillin
MIC > 4µg/ml
MRSA
ORSA
• CDC:
Defining c-MRSA
 Illness Compatible with Staphylococcal Disease
 MRSA Cultured from site
 Outpatient Setting
 Hospital admission: < 48 hours
 No Admission within the past year:
❁Health Care Facility
❁Surgery
❁Dialysis
❁Permanent Indwelling Catheter
❁Percutaneous Medical Device
MMWR 2004;53:767-70
History
•
•
•
•
•
•
•
cMRSA Outbreak
MarchDec 1980
Henry Ford Hospital
40 Patients
Linked to IVDU
Antibiotic Exposure
Limited antimicrobial
data
Saravolatz LD etal., Ann Int Med 1982;96:11-16
History
• Brian MJ, Ped Infect Dis J 1989
• Taylor G etal., Can J Infect Dis 1990
• Udo EE etal., J Hosp Infect 1993
• Pate KR etal., Lancet 1995
• Maguire GP etal., Med J Aust 1996
• Heffernan H etal., LabLink 1997
• Durmaz B, J Hosp Infect 1997
• Collignon P etal., Lancet 1998
• Herolds BC etal., JAMA 1998
History
History
C-MRSA
Epidemic
Potential
SSTI
Non
β-Lactam
Susceptible
Poor
Hygiene
History
• 4 Fatal Pediatric cMRSA infections
• Bacteremia Sepsis
• Non-multiresistant Strains
• Distinct: Nosocomial
• Typing: Related
MMWR 1999
Specialized MRSA surveillance project in
2001
Active Bacterial Core Surveillance program:
❁Population-based
❁Epidemiologic Features
❁Invasive Bacterial Diseases
Fridkin etal., April 7, 2005
MRSA
Active Bacterial Core
Surveillance Project
Baltimore
Hospital: 11
Population: 700,000
Duration: 12 M
Feb 2002
Atlanta
Health District
Counties: 8
Population: 3.3 million
Duration: 18 M
July 2001
Minnesota
Hospital Labs: 12
Duration: 24 M
Jan 2001
7819
MRSA
0
3714
MRSA
0
1000
2000
4000
6000
1720
147
C-MRSA
2000
12%
3000
8000
MRSA
370
C-MRSA
20%
1590
C-MRSA
4000
0
500
1000
8%
1500
2000
Moran GJ etal, August , 2006
Moran GJ etal, August , 2006
 SSTI: 422 patients S.aureus: 320 patients (76%)
 MRSA: 249 Patients (78%)
 OVERALL Prevalence: 59 % (15  74%).
 Pulsed-field type USA300: 97 %
 SCCmec type IV & Panton–Valentine leukocidin toxin gene: 98 %
 Susceptibility:
❁ Clindamycin: 95 %
❁ Erythromycin:6 %
❁ Fluoroquinolones: 60%
❁ Rifampin: 100%
❁ TMP-SMX: 100%
❁ Tetracyclin: 92%
❁ Discordant Antibiotic Therapy:100/175 patients (57 percent).
Prepared by Anne R. Sites, MPH
www.mainpublichealth.gov
Infectious Disease Epidemiology Report
2004-05
• Annual Average: 111 Cases
• Incidence Rate: 8.6 cases/100,000 Population
• Gender: Male (57 %)
• Race: 94% White
“Information available for 68 cases”
Infectious Disease Epidemiology Report
2004-05
Infectious Disease Epidemiology Report
2004-05
Infectious Disease Epidemiology Report
2004-05
Infectious Disease Epidemiology Report
2004-05
Four clusters
26MRSA skin infections
The final sources of infection were not determined
Risks factors:
● Sharing of personal items
● Assisting in changing of wound dressings
● Tattooing
Common Presentation
Younger Patients
 No risk Factors
 Boils/ Abscesses
Skin & Soft tissue Infections
Epidermis/Dermis
•Impetigo
•Folliculitis
•Erysipelas
•Ecthyma
•Furuncle
•Carbuncles
Impetigo
http://www.iskin.co.il/_Uploads/83Impetigo.jpg
Folliculitis
http://www.lib.uiowa.edu
Furuncle
http://www.brooksidepress.org
Erysipelas
http://images.google.com
Ecthyma
Ecthyma
http://www.lib.uiowa.edu
FURUNCLES “ BOILS”
http://missinglink.ucsf.edu
CARBUNCLES
http://dermatlas.med.jhmi.edu/derm
Skin & Soft tissue Infections
Subcutaneous Tissue
Cellulitis
Skin & Soft tissue Infections
CELLULITIS
CELLULITIS
CELLULITIS
Skin & Soft tissue Infections
Fascia
Necrotizing
Fasciitis
Necrotizing Fasciitis
www.lib.uiowa.edu
Skin & Soft tissue Infections
Muscle
Myonecrosis
Necrotizing Fasciitis/Myonecrosis
www.afids.org
www.dermatologytimes.com
Photo: Brian Machler, M.D.
Young, D. M. et al. Arch Surg 2004;139:947-953.
Copyright restrictions may apply.
Serious Infections
Case Reports
 Bacteremia
“MMWR 1999”
 Osteomyelitis/ Pyomyositis
“ Pate et al., Lancet 1995”
 Sepsis Syndrome
“Mongkolrattanothai K etal, CID , 2003”
Necrotizing Pneumonia “Empyema”
Francis JS etal., CID Jan 1, 2005
April 2006
29 yo lady
Asthmatic, EX IVDU (5 years ago)
Nodular
MULTIFOCAL
Endocarditis
Johns Hopkins University Hospital, Baltimore, MD.
Retrospective chart review: 12 months
Positive blood cultures
No risk factors for MRSA acquisition
Modified Duke's criteria: Five / 193 patients.
Isolates: PVL gene positive
Type IV SCCmec element.
 PFGE: Skin isolate identical to blood isolate
Bahrain M. et al, Scand J Infect Dis. 2006;38(8):702-7.
Necrotizing Fascitis
Jan 03  Apr 04
Retrospective, Cohort
Los Angeles, CA
MRSA:
843 Pts “Wound”
14 Pts “ NF”
Miller et al. NEJM,52 (14):April 7, 2005
Purpura fulminans
University of Minnesota Medical School: 5 Cases
20002004
Kravitz GR etal., CID April 1 2005
Purpura fulminans
University of Minnesota Medical School: 5 Cases
20002004
Kravitz GR etal., CID April 1 2005
Virulence of c-MRSA
Virulence of c-MRSA
Doubling Times
28.79 +/- 7.09
min
Community
38.81 +/- 7.01
min
Nosocomial
Okuma K etal, J Clin Microbiol 2002
Virulence of c-MRSA
• Discovered in 1894 “van de Velde”
• Distinguished in 1932 “ Panton & Valentine”
• Genes enters via a bacteriophage
Gamma
Haemolysins
PVL
Van de Velde, Cellule 1894
Panton PN, Valentine FCO, Lancet 1932
Timothy J. Foster , J Clin Invest 114:1693-6, 2004
Virulence of c-MRSA
PVL
Dermonecrotic
Toxin
Affinity
Collagen & Laminin
SSTI
“Boils/ Impetigo”
Necrotizing
Pneumonia
Mortality
Genetic Backgrounds of 117 cMRSA strains
“US, France, Switzerland, Australia, New Zealand & Western Samoa”
100
90
PVL
80
SCC mec IV
70
Hemolysin G
60
Enterotoxin A
50
Enterotoxin B
40
Enterotoxin C
30
Enterotoxin D-J
20
10
Enterotoxin H
Entertoxin K
0
Vandenesh F et al., Emerg Infect Dis 2003
• Is NOT a Universal Marker of cMRSA
• At least 4 epidemics “Australia”: No PVL Gene
New South Wales
100 Islates
68%
PVL
4%
Toxic Shock-Syndrome
Toxin-1
25 %
Enterotoxin Genes
Barbagiannakos T etal, Int. Symposium Staph. & Strep. Infection, Oct 2004
O’Brien FG atal., J Clin Microbiol 2004
• Is it the Major Virulence Determinant in C-MRSA
Disease?
• Mouse infection models: PVL-positive versus PVLnegative
• Strains lacking PVL were as virulent in mouse sepsis
and abscess models as those containing the leukotoxin.
Voyich JM etal., JID 194,2006
PVL-negative
strains were as
lethal as wildtype strains in a
sepsis model, and
they caused
comparable skin
disease.
Voyich JM etal., JID 194,2006
IVDU
Playing
Contact
Sports
Previous
Antimicrobials
Man
Who has sex
With men
Steam
Baths
Clients
Community
MRSA
Resident of
Developmental
Disabled
Institutions
Incarceration
In
Goal
Being a
Military
Recruit
IVDU
• First reports in Detroit
• Subsequently many report “San Francisco”
• Not Universal “ Not shown in Australian
studies”
♦ Saravolatz LD etal., Ann Intern Med 1982
♦ Charlebois ED etal., Clin Infect Dis 2002
♦ Young DM etal., Arch Surg 2004
Contact Sports
♦ Stacey AR etal., Br J Sports med 1998
♦ Lindenmayer JM etal., Arch Intern Med 1998
♦ MMWR 2003
Kazakova et al. February 3, 2005
Epidemic-Curve Graph (Top) & Field Position
Diagram (Bottom): MRSA cases among St. Louis
Rams Professional Football Players “2003”
Box on graph & field diagram= MRSA infection
Different colors= different players
Boxes of same color= recurrent infections.
X = Defensive-player position
O= Offensive-player position.
Kazakova et al. February 3, 2005
•
•
•
•
•
Retrospective cohort study
Nasal Swab Survey
84 St. Louis Rams football players & staff members.
S. aureus analyzed by PFGE & Gene typing
During the 2003 football season:
●8 MRSA infections: 5/58 Rams players (9 %)
●All infections developed at turf-abrasion sites
●Infection was significantly associated with the
lineman or linebacker position & higher BMI.
●MRSA : whirlpools and taping gel
●MRSA : 35/ 84 nasal swabs from players and
staff members (42%).
●MRSA : competing football team had PFGE patterns that were
indistinguishable from those of the Rams'
●MRSA: All positive PVL & SCC mec type IVa resistance
August 22, 2003 / 52(33);793-795
Methicillin-Resistant Staphylococcus aureus
Infections Among Competitive Sports Participants
Colorado, Indiana, Pennsylvania, and Los Angeles
20002003
Prison Incarceration
•
•
•
•
•
Several Epidemic reports
Boils/Abscesses/Invasive disease
Strain: USA300
Carriage: Inmates & Goalers
Factors:
♦ Hygiene
♦ Poor access to health care
♦ Lack of MRSA recognition
• CDC: MMWR Rep 2003;52:992-6
Georgia, California & Texas
Prison Incarceration
MMWR Weekly October 26, 2001
MRSA SSTI in a State Prison --- Mississippi, 2000
Prison Incarceration
May 30th, 2005: One week
Two Maine Correctional Facilities
SSTI: 11 Inmates
No evidence of direct connection
None among correctional officers or other staff
Military Service
Brooke Army Medical Center
Fort Sam Houston, TX
1994-1997
67 Cases
SSTI
24 (36%)
C-MRSA
Baum SE Mil Med 2003
Military Service
Military Medical Facilities,San Diego
19902004
1888 MRSA Cases
“1227” 65 % C-MRSA
Incidence
155/100K person-year “2004”
Type IV
Crum N etal., Am J Med Oct 2005 (43rd IDSA Abstract)
Homosexuality
• Outbreaks reported
• Boils
• Investigation in process
• Sexual behavior & Drug use
Garthwaite T: http://www.lapublichealth.org/std/MRSAproviders.pdf
MMWR Reb 2003;52:88
Tattoo Recipients
Ohio, Kentucky, and
Vermont, 2004-2005
Six unlinked clusters
44 recipients
13 unlicensed tattooists
Potential Causes:
❁Nonsterile equipment
❁Suboptimal infectioncontrol practices
MMWR;June 23, 2006 / 55(24);677-679
Other Reported Risk Factors
Alaskan
Sauna
Use
Landen MG, West J Med 2000
Day Care Center
Toronto
Canada
Huang YC, Pediatr Infect Dis J 2004
Strategies for Clinical Management “1”
Skin
Abscess
“Spider Bite”
Purpura
FUlminans
Sepsis
Syndrome
Necrotizing
Fascitis
Endocarditis
Pneumonia
Osteomyelitis
Septic
Arthritis
Strategies for Clinical Management “2”
Fluid
“Purtulent lesions
Abscess Cavity”
Bone
Respiratory
“Sputum
DTA
BAL
Pleural Fluid”
Specimen
“Cutlure
&
Susceptibility”
Joint
Blood
Strategies for Clinical Management “3”
Routine Nasal Cultures: Not necessary
Molecular typing: No information
Incision and drainage:
✾ Routinely
✾ Fine Needle Aspirate
CLINDAMYCIN
•
•
•
•
Advantages
FDA Approved
“S.aureus”
Widely Used
Reports of Success
Prevent Toxin Production
•
Disadvantages
Not FDA approved MRSA
• Clostridium difficile
• Children ?!
Faden H, etal, Pediatr Infect Dis J, May 2001
Frank AL etal., Pediatr Infect Dis J, June 2002
Marcinak JF etal., Curr Opin Infect Dis , June 2003
CLINDAMYCIN
Inducible MLSB Phenotype
Efflux to Macrolides
Fully Susceptible
D-Zone Test
Tetracyclines
•
•
•
•
Advantages
Doxycyline: FDA
Approved “S.aureus”
Small Case Series: SSTI
? Minocycline
? Doxycycline
Ruhe JJ etal., CID May 2005
•
•
•
•
•
Disadvantages
Not FDA approved MRSA
Little Information
Not for Invasive
Pregnancy
Children
Tmp-Smx
Disadvantages
Advantages
• Several Successful
•
Case Reports
Small Case Series:
SSTI
•
•
•
•
Ardati KO etal., J Pediatr 1979
Jemni L etal., CID 1994
Seligman SJ etal., J Infect Dis 1973
Stein A etal., Antimicro Agents Chemo 1998
♦Markowitz N, Ann Intern Med 1992
Not FDA approved MRSA
Not for Invasive♦
3rd trimester Pregnancy
Infants < 2 Months”
Rifampin
• Should not be used as a single agent
• Used in combination
• Achieves high concentration in Mucosal surfaces  ?
•
•
promote eradication of MRSA coverage
? Benefit
Drug-Drug interactions
Yu VL etal, NEJM Jul 10, 1986
Linezolid
• FDA approved: Complicated SSTI & HAP “adults”
• Myelosuppression “Dose & Duration dependent”
• Case reports:
. Peripheral neuropathy
. Optic Neuropathy
. Lactic acidosis
• Cost
• Resistance
Apodaca AA, NEJM Jan 2003
Bressler AM, Lancet Infect Dis August 2004
Lee E etal., CLin Infect Dis Nov 2003
Tsiodras S etal., Lancet July 2001
Not Optimal
Fluoroquinolone
Macrolides
Fluoroquinoloes
• Ciprofloxacin & Levofloxacin:
Complicated SSTI
• Moxifloxacin & Gatifloxacin:
Uncomplicated SSTI
• None: MRSA infections Resistant mutantsReplase & Rx
Failure
•Blumberg HM etal., J Infect Dis June 1991
•Piercy EA etal., Antimicrob Agents Chemother , Jan 1989
•Jones ME etal, Antimicrob Agents Chemother, June 2002
Macrolides/Azalides
• Erythromycin/ Clarithromycin & Azithromycin:
Uncomplicated SSTI
• MRSA: No data
• Resistance: Common “ MRSA”
Fridkin SK etal, N Engl J Med, April 2005
Vancomycin
Quinpristin
/
Dalfopristin
Tigecyclin
Ceftaroline
Parentral
Agents
Telavancin
Teicoplanin
Daptomycin
Linezolid
Dalbavancin
More…
Oritavancin
Investigational
Agents
Tedozolid
Ceftobiprole
I.
II.
III.
IV.
Keep draining wound covered : dry clean bandages
Regular hand cleaning: Soap and water or alcohol based hand gel
Maintain good general hygiene “regular bathing”
No items sharing: Towels, clothing, bedding, bar soap, razors, and
athletic equipment that touches the skin
V. Launder clothing that has come in contact with draining wound
after each use and dry thoroughly
VI. If not able to cover wound, do not participate in athletic
activities until your wound is completely healed
VII. Clean equipment and other environmental surfaces with OTC
disinfectants/detergents.
Decolonization Strategies
•
•
•
•
•
2005: EIN
471 Respondents
6800 Patients
86%: Nasal Decolonization “4200 patients”
57%: Family Decolonization “1800 patients”
Steven C. Buckingham
October , 2006
Intervention
Recommending (%)
Topical therapies
Chlorhexidine gluconate
70
Hexachlorophene
14
Antibacterial Soap
3
Household bleach
3
Tea tree oil
<1
Alcohol-based hand sanitizer
<1
Intranasal Therapies
Mupirocin
92
Bacitracin
3
Chlorhexidine gluconate
<1
Oral Therapies
Rifampin
43
TMP/SMX
37
Clindamycin
8
Minocyclin
8
Doxycuclin
5
Linezolid
<1
Alcohol-based Hand Sanitizers
60-95% Alcohol
Broad range of pathogens
Versus Standard hand washing:
●More effective among health care workers
Versus Plain/Antimicrobial Soap:
●Less Skin irritation & dryness
MMWR 2002;51:1-45
Antimicrobial Soap
Active ingredients: Triclocarban or Triclosan
No evidence of superiority over plain soap
Larson EL etal, Amm Intern Med 2004;140:321-9
Hexachlorophene
Bisphenol: 1950’s
Neurological toxcitiy “ infants”
FDA: not safe & effective
Chlorhexidine Gluconate
Cationic bisbiguanide
USA: 1970s
Antimicrobial Activity:
● Broad: Gram-positives
● Modest: MRSA “ Comparable to plain soap”
 Dermatitis
 Cost
Hunag Y etal., Am J Infect Control 1994
Guilhermetti M etal., Infect Control Hosp Epidemiol 2001
Povidone/Iodine
More active against MRSA
More Skin irritation
Systemic absorption can occur
Block SH, Cutis 1980
Household Bleach
Active Ingredient: Sodium Hypochlorite
1847: Semmelweis
Not intended: Personal use
Safety & Efficacy: Not established
Skin Irritation & Odor
Systemic Antimicrobials
Insufficient Evidence
Antimicrobial Resistance
Intranasal Mupirocin
Can eradicate Nasal Carriage
Reestablishment: 6-12 months
Efficacy: MRSA < MSSA
Resistance: Emerging
Doebbeling BN etal., CID 1993
Doebbeling BN etal., Arch Intern Med 1994
Tea Tree Oil
Volatile essential oil
 Melaleuca alternifolia
Variety products:
Soaps, shampoo, creams…
Nasal eradication:
Less effective than mupirocin
Safety profile: Not established
Dryden MS etal., J Hosp Infect 2004
• Randomized Controlled trial
• 87 Rxed Patients vs 25 Placebo; 7 Days
Course of:
– 2% chlorhexidine gluconate washes
– 2% mupirocin ointment intranasally
– Oral rifampin
– Oral doxycycline
• At 3 months F/U:
– 74% of Rxed Pts. had Cx Negative vs 32% of
those not treated (P=.0001)
Simor AE etal., CID, Jan 15th 2007, 17885