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COMMUNITY ACQUIRED MRSA

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COMMUNITY ACQUIRED MRSA Pisespong Patamasucon, M.D. Pediatric Infectious Disease UNSOM - Las Vegas TIMELINE FOR RESISTANCE IN HOSPITALS AND THE COMMUNITY Resistant ... – PowerPoint PPT presentation

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Title: COMMUNITY ACQUIRED MRSA


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
25 Resistance 25 Resistance
Introduced Reported in Hospitals
in Community (Year) (Years)
(Years)
(Years) Penicillin 1941 1 to 2
6 15 to 20 Methicillin 1961
lt1 25 to 30
40 to 50 (Estimated) Vancomycin
1954 gt40 ? ?
1) Emerg. Infect. Dis 2001 7178-182 2)
N.Engl.J.Med 20033481342-1347
3
Resistant staphylococci Definitions
Resistance MIC gt 16 µg methicillin/mL MIC gt 4
µg oxacillin/mL Species MRSA Methicillin-resista
nt 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 48-72 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
  • 1995 - Switzerland
  • 20 MRSA isolated were CA
  • 36 never been hospitalized



Layton MD et al. Infect.Control Hosp Epiderm
19951618-24
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 4289-4294

9
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10
Comparison of Staphylococcal Cassette Chromosome
mec Types
ccr, cassette chromosome recombinase RE, right
extremity of SCCmec element
Adapted from J Infect Dis. 2002 1861344-1347
11
MRSA bacteremia is associated with significantly
higher mortality rate than MSSA
bacteremia. (adds ratio 1.93 95 C.I, 1.54 -
2.42 Plt.001)
CLIN. INFECT. DIS 2003 3653-59
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 115674-680 CLIN INFECT
DIS 2000 30368-373
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
  • 4. Use of antibiotic in the communities

15
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 279593-598
16
CA-MRSA DISEASE OUTBREAKDAY-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 178593-598
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). Ov
erall prevalence of MRSA was 2.8
CLIN. INFECT. DIS 2002 34 425-433
18
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 48707-710
19
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 9486-493
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 322858-2862
21
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 36131-139
22
CA - MRSA in South Texas Children
  • 7 cases 1990-1996 MRSA
  • 53 cases 1997-2000 (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 200120860-863.
23
Four Pediatric Deaths from Community-AcquiredMeth
icillin-Resistant Staphylococcus aureus
Minnesota and North Dakota, 1997-1999
Characteristic Case 1 Case 2
Case 3 Case 4 Age 7
years 16 months 13
years 12
months Syndrome septic arthritis,
severe sepsis necrotizing
necrotizing sepsis,
pneumonia, pneumonia, pneumon
ia/ 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,
tettetracycline, cipciprofloxacin,
gentgentamicin eryerythromicin,
clindclindamycin, and vancvancomycin. SEBstaph
ylococcal enterotoxin B SECstaphylococcal
enterotoxin C.
24
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 50277-280.
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 2003 53792-795
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) 793-795.
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)

28
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29
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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
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 PERSISTENCEOF CARRIAGE
OF MRSA
  • Cultures of the Nares (sensitivity 93 negative
  • predictive value 95)
  • Cutaneous sites of axilla, groin and perineum
  • (sensitivity lt39, negative predictive value
  • lt69)
  • Duration of carriage more than 3 years

CLIN INFECT DIS 1994 191123-1128
34
Susceptibility of CA-MRSA isolates identifiedat
selected Minnesota hospitals, 1996 - 1998
Antibiotic Susceptible Intermediately
Resistant () Susceptible
() () Ciprofloxacin 93
3 3 Clindamycin 93
1 6 Erythromycin
64 9 27 Gentamicin
97 1 2 Oxacillin
0 0 100 Rifampin
99 1 0 Tetracycline
95 0.4 5 TMP-SMZ
97 0 3 Vancomycin
100 0 0
CLIN. INFECT DIS 2001 33990-996
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 79497-508

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 851-17
37
Treatment
  • 2001 in Minnesota 354 patients with CA-MRSA 83
    were treated initially with Beta-Lactam
    antibiotics

CLIN. INFECT. DIS 2001 33990-996
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 7178-182
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 (contd)
  • TMP/SMX
  • Synergistic combination of trimethoprim/sulfametho
    xazole
  • 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
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43
SUGGESTION outpatient MANAGEMENTOF 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-MRSA
RX
  • 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 47196-203
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
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