1. COMMUNITY ACQUIRED MRSA
Pisespong Patamasucon, M.D.
Pediatric Infectious Disease
UNSOM - Las Vegas

2. TIMELINE FOR RESISTANCE IN HOSPITALS AND THE COMMUNITY
Drug Drug Resistance % Resistance % Resistance
Introduced Reported in Hospitals in Community
(Year) (Years) (Years) (Years)
Penicillin to to 20
Methicillin < to to 50
(Estimated)
Vancomycin > ? ?
1) Emerg. Infect. Dis 2001; 7:
2) N.Engl.J.Med 2003;348:

3. Resistant staphylococci: Definitions
Resistance
MIC > 16 μg methicillin/mL
MIC > 4 μg oxacillin/mL
Species
MRSA: Methicillin-resistant S aureus
MRCNS: Methcillin-resistant coag-neg staphylococci
(S epidermidis most common)

4. CRITERIA OF CA-MRSA
Isolated from patients residing in the community or within hours of hospitalization
(Problem: can be acquired in few hours and MRSA chronic carrier)
Risk factors for MRSA is usually absence
Susceptibility of the organism to various antibiotics
Genome make-up

5. Introduction MRSA is becoming widespread in multiple communities
MRSA pts have no epidemiological links with each other
Indicated MRSA may be becoming ENDEMIC like S. aureus to Penicillin
No reliable way to distinguish pts with MRSA from pts with MSSA at the time of admission

6. INTRODUCTION Historical
CA-MRSA - IV Drug users, recent hospitalization or resident in a nursing home
1995 Yale - New Haven Hospital
36% MRSA isolated were community acquired
Switzerland
20% MRSA isolated were CA
36% never been hospitalized
Layton MD et al. Infect.Control Hosp Epiderm
1995;16:18-24

7. Characteristics of Strains
Hospital acquired MRSA highly resistant to multiple
antibiotics except Vanco, Rifampin, Gentamicin.
Community acquired MRSA sensitive to TMP/SMZ,
Rifampin, Clindamycin/Erythromycin,
Linezolid, Vancomycin and also Quinolones
except Penicillin and Cephalosporin

8. CA - MRSA Distinguishing Features
Absence of Hospital - Associated risk factors
Susceptibility to most antibiotics other than Beta-lactams
Distinct genotypes from HA-MRSA
Presence of Type 4 staphylococcal chromosomal cassette mec (the element that contains the methicillin resistance determinant)
Presence of genes encoding for toxins (Pantone-Valentine Leukocidin and many Staph Enterotoxins)
J. CLIN. MICROBIOL 2002; 40:

10. Comparison of Staphylococcal Cassette Chromosome mec Types
SCCmec Type
ccr Gene Type
mec Complex Type
Size (kb)
RE Type I 1 B
34.3 i II 2 A
53.0 ii
III 3
66.9
iii IV
ccr, cassette chromosome recombinase; RE, right extremity of SCCmec element
Adapted from J Infect Dis. 2002; 186:

11. MRSA bacteremia is associated with
significantly higher mortality rate than
MSSA bacteremia.
(adds ratio 1.93; 95% C.I, ; P<.001)
CLIN. INFECT. DIS 2003; 36:53-59

12. PROBLEMS OF NEW CA-MRSA
Treatment failure with accompanying
complications or death (if Beta-lactam antibiotic
is used)
MRSA strains may be more difficult to threat or
more expensive to treat
Vancomycin is inherently less efficacious
ANN INTERN MED 1991; 115:
CLIN INFECT DIS 2000; 30:

13. ORIGIN OF CA-MRSA Majority (58%) of infections were from hospital
and long term care facilities
Injection drug use was associated with unrelated
healthcare settings.
In an outbreak situation MRSA strains are now originated from the community
CLIN. INFECT. DIS 2004; 39: 47-54

14. Reasons why this CA-MRSA occurs:
1. S aureus is part of normal flora in 20-30% of healthy persons
2. No different in adhesion to nasal epithelial cells between MRSA and MSSA
3. Pts discharged from Hospital with MRSA may remain colonized for a long period thus providing a reservoir to communities
Use of antibiotic in the communities

15. A study from Chicago found a 25 fold increase in
CA-MRSA in Pediatric
A study from Chicago found a 25 fold increase in
the number of children admitted to the hospital with
an MRSA infection who lacked an identified risk
factor for prior colonization.
JAMA 1998; 279:

16. CA-MRSA DISEASE OUTBREAK DAY-CARE CENTER AND MRSA
Survey of two day-care centers in Dallas, Texas each with index
case of MRSA infection, found 3% and 24% of children in the
respective centers were colonized. The isolates were
susceptible to multiple antibiotics. Forty percent of colonized
children had no risk factor.
J. INFECT DIS 1998; 178:

17. MRSA in Community 2000
A population based community sample of 833 homeless
and urban poor in San Francisco 22.8% were colonized
with S. aureus (12.0% of S. aureus isolated were Methicillin-
resistant).
Overall prevalence of MRSA was 2.8%
CLIN. INFECT. DIS 2002; 34:

18. CDC four pediatric deaths from community-
Major Impact
CDC four pediatric deaths from community-
acquired Methicillin resistant staphylococcus
aureus -- Minnesota and North Dakota, 1997.
[No risk factors, susceptible to several antibiotics
and PFGE related]
MMWR MORB MORTAL WKLY REP 1999; 48:

19. SCC mec element often is isolated from
CA-MRSA
SCC mec element often is isolated from
staphylococcus epidermidis residing on the skin of
healthy individuals, suggesting that the SCC mec
gene was transferred from S. epidermidis to commensal
S. aureus
Trends. Microbiol 2001; 9:

20. EPIDEMIOLOGY OF CA-MRSA
Actual prevalence in USA is not known but reported from Vermont to California (Nationwide problem)
Canada
Europe
Australia
Middle East
The South Pacific
J. CLIN. MICROBIOL 1999; 32:

21. Estimated CA-MRSA Prevalence of 1.3%
RECENT META - ANALYSIS FROM 10 STUDIES WITH SURVEILLANCE CULTURES IN THE COMMUNITY (Population of 8350)
Estimated CA-MRSA Prevalence of 1.3%
CLIN. INFECT DIS 2003; 36:

22. CA - MRSA in South Texas Children
7 cases MRSA
53 cases (35 cases alone in 2000) MRSA
48/53 (91%) soft tissue infection
More susceptible to SMZ /TMZ (98% vs 82%) and Clinda 92% vs 57%) and less susceptible to tetracycline 54% vs 95% than
nosocomial MRSA.
Majority of CA-MRSA had no risk factors
Pediatr Infect Dis 2001:20:

23. Four Pediatric Deaths from Community-Acquired Methicillin-Resistant Staphylococcus aureus Minnesota and North Dakota,
Characteristic Case Case Case Case 4
Age 7 years months years months
Syndrome septic arthritis, severe sepsis necrotizing necrotizing
sepsis, pneumonia, pneumonia,
pneumonia/ severe sepsis severe sepsis
Antimicrobial t/s, tet, cip, gent, t/s, tet, cip, gent, t/s, cep, cip, gen,t t/s, tet, cip, gent,
susceptibility* ery, clind, vanc ery, clind, vanc ery, clind, vanc ery, clind, vanc
Toxin Test† SEC positive SEC positive SEB positive SEB positive
*t/s = trimethoprim-sulfamethoxazole, tet=tetracycline, cip=ciprofloxacin, gent=gentamicin
ery=erythromicin, clind=clindamycin, and vanc=vancomycin.
†SEB=staphylococcal enterotoxin B; SEC=staphylococcal enterotoxin C.

24. From 41 cultures from 853 patients
CA-MRSA Skin Infection in Outpatient University Health Center - Houston, Texas 2003
From 41 cultures from 853 patients
10/19 (53%) patients with S. aureus has MRSA
5 patients with risk factors (3 treated with antibiotics, 2 exposed to household)
Clinical presentation: abscesses (73%) or cellulitis (64%), pustules (27%), nodules and papules (27%) and crusted plaque
MSSA: head and neck
MRSA: lower extremities.
J Am Acad Dermatol 2004; 50:

25. Clusters of MRSA Among Sports Team
September 2000 in Pennsylvania
Affected college and high school football players and wrestlers 2-10/team, 7/10 hospitalized. Risk factors: skin trauma, shaving and sharing unwashed towels.
September 2002 in L.A.
2 skin infections, 1 hospitalized sharing lotions and lubricants
January 2003 in Indiana
2 wrestlers, no common exposures.
MMWR :

26. CA - MRSA in Outbreak of Athletics
Contributing factors:
Skin trauma either from abrasion or from clothing
Direct contact with infected person
Sharing uncleaned equipment and personal items or laundered.
MMWR 52 (33);

27. Outbreaks of CA-MRSA Skin Infection in L.A. 2002-2003
- L.A. county jail (largest 165,000 persons/yr). 928 MRSA skin infections diagnosed in 2002 having “spider bites”.
- 39/66 hospitalized cases, 10 with invasive disease (bacteremia, endocarditis and osteomyelitis).
- Pulsed-field gel electrophoresis likes other community outbreaks in U.S.A.
MMWR 2002; S1 (No. RR16)

30. D TEST The circular area around Clindamycin with a flat
or blunted edge adjacent to erythromycin is proof
of inducible resistance to Clindamycin.

31. Resistant staphylococci: The diagnostic challenge
Heteroresistance:
Heterogeneity of resistance within each strain
Two subpopulations within same strain:
- Resistant
- Susceptible
Relative number of resistant and susceptible cells varies from culture to culture
Thus, resistant strains often escape detection in vitro

32. (eg., abscesses, cellulitis, impetigo, furuncles).
CLINICAL PRESENTATIONS
Currently, most infections caused by CA-MRSA are
skin infections
(eg., abscesses, cellulitis, impetigo, furuncles).
Other types of infection: Otitis, Pneumonia, Bursitis,
Osteomyelitis, Septic arthritis and Blood stream
infections.

33. DETECTION and LONG TERM PERSISTENCE OF CARRIAGE OF MRSA
Cultures of the Nares (sensitivity 93% negative
predictive value 95%)
Cutaneous sites of axilla, groin and perineum
(sensitivity <39%, negative predictive value
<69%)
Duration of carriage more than 3 years
CLIN INFECT DIS 1994; 19:

34. Susceptibility of CA-MRSA isolates identified at selected Minnesota hospitals, 1996 - 1998
Antibiotic Susceptible % Intermediately Resistant
(%) Susceptible (%)
(%)
Ciprofloxacin
Clindamycin
Erythromycin
Gentamicin
Oxacillin
Rifampin
Tetracycline
TMP-SMZ
Vancomycin
CLIN. INFECT DIS 2001; 33:

35. TMP-SMZ and CLINDAMYCIN* SIMILAR BIOAVAILABILITY ORAL OR IV
GOOD OPTIONS FOR OUTPATIENT
OF CA-MRSA
NOTE: Clindamycin should be used only if organism is
sensitive to erythromycin
MED CLIN NORTH AMER 1995; 79:

36. RX
Fluoroquinolones are an option in adult patients with
CA-MRSA; however, single-step mutations can lead to
resistance.
The nosocomial MRSA developed resistance to these drugs
after their introduction, so consider combining them with
a drug like Rifampin to decrease emergence of resistance.
MED. CLIN. NORTH. AMER 2001; 85:1-17

37. Treatment
2001 in Minnesota 354 patients with CA-MRSA 83% were treated initially with Beta-Lactam antibiotics
CLIN. INFECT. DIS 2001: 33:

38. Beta-lactam antibiotics are ineffective against
CA-MRSA. Given the potential aggressiveness
and virulence of the bacterium, an inappropriate
antibiotic choice could result in significant
morbidity and even death.
EMERG. INFECT. DIS 2001; 7:

39. Therapeutic choices in the treatment of resistant staphylococcal infections
Vancomycin
Proven effective as initial I.V. therapy for a variety of MRSA infections
Potential for ototoxicity and nephrotoxicity limit usefulness as long-term therapy
Teicoplanin
Same class of drugs as vancomycin
Appears to have comparable efficacy and to be better tolerated, particularly by I.M. injection
Longer half-life

40. Therapeutic choices in the treatment (cont’d)
TMP/SMX
Synergistic combination of trimethoprim/sulfamethoxazole
Demonstrated in vitro and in vivo activity against resistant staphylococcal species
Use may be limited to mild MRSA infections
Minocycline
Most active tetracycline against resistant staphylococci
Can be given I.V. or p.o.
Commonly used in Japan against MRSA and MRCNS
US experience limited, but early clinical results demonstrate high activity plus low potential for toxicity and make it an alternative for long-term oral follow-up as well as short-term parenteral use in-hospital

41. Therapeutic choices in the treatment of resistant staphylococcal infections
Rifampin
Exhibits activity against staphylococci and a wide range of other organisms
Rapid development of resistance in vitro and in vivo may limit its use to combination therapy
New quinolones
High in vitro activity against resistant staphylococcal species
Can be given p.o.
Rapid development of resistance to ciprofloxacin in vivo by MRSA has been reported

42. Presentation Folliculitis/Pustular lesions, Abscess, Cellulitis
I & D Obtain specimen for culture and sensitivity
Mild
Moderate
Severe
Toxic appearing Immunocompromise Limb-threatening
Critically ill
I & D alone may be adequate
I& D
Oral Abx TMP/SMX,Clindamycin,Doxycycline
Close followup
Hospitalize
Empiric Vanco or clinda
Empiric Vanco PLUS naficillin +/- gentamicin

43. SUGGESTION outpatient MANAGEMENT OF Recurrent CA-MRSA Skin Infection
Check sensitivities of MRSA to TMP-SMZ, Rifampin, Clindamycin,
Erythromycin, Vancomycin and Linezolid
Treat with TMP-SMZ ± Rifampin or Clindamycin ± Rifampin
depending on sensitivity
Prescribe Mupirocin (Bactoban) cream to anterior Nares twice a day
x 5 days to eradicate nasal colonization
Recommend bathing the patient with hibiclen from the neck down
daily for 3 consecutive days to eradicate skin colonization

44. RESERVE DRUG(s) FOR CA-MRSARX
RESERVE DRUG(s) FOR CA-MRSA
VANCOMYCIN - in patient [only IV form]
LINEZOLID, Oxazolidinones
new antibiotic class [IV and P.O.]
also effective against VRE and also MRSA
Synercid

45. DISEASE TRANSMISSION
Person to person contact or contact with contaminated fomites, e.g. familial transmission, non-familial outbreak (football team and wrestling teams).
Molecular analysis of various outbreaks in the USA (Minnesota, North Dakota, Nebraska and Alabama) found to be closely related or identical.
Antimicrob. Agents Chemother 2003; 47:

46. CA-MRSA MEASURES TO PREVENT SPREADING
Instruct patient in hand washing
Sharing of personal items (eg. athletic
equipment, towels) should be avoided
Compliance with antibiotic treatment
course

47. CA - MRSA Competitive Sports
Transmission control measures
Increase hand hygiene
Showering with soap every practice or tournament
Covering cuts/abrasions until healed
Laundering personal items after each use
Cleaning or laundering shared equipment at least once a week
Establishing a routine cleaning sensor wire (fencing)
Consult M.D. for unhealed or infected wound

48. “Antimicrobial resistance to Penicillin, Methicillin, or
Vancomycin is an unavoidable consequence of the selective
pressure of antibiotic exposure. The quest is not whether
resistance will occur, but how prevalent resistance will
become.”
Minimizing the antibiotic pressure that favors the selection
of resistant strains is essential in controlling the emergence
of these strains.
Henry F. Chambers, M.D.
Professor of Medicine
Chief of Infectious Diseases
at San Francisco General Hospital
February 2004