Transcript HOSPITAL ACQUIRED MRSA

COMMUNITY ACQUIRED
MRSA
Pisespong Patamasucon, M.D.
Pediatric Infectious Diseases
UNSOM - Las Vegas
TIMELINE FOR RESISTANCE IN
HOSPITALS AND THE COMMUNITY
25%
Resistance in
Hospitals
(Years)
25%
Resistance in
Community
(Years)
Drug
Introduced
(Year)
Resistance
Reported
(Years)
Penicillin
1941
1 to 2
6
15 to 20
Methicillin
1961
<1
25 to 30
40 to 50
(estimated)
Vancomycin
1954
>40
?
?
1) Emerg. Infect. Dis 2001; 7:178-182
2) N.Engl.J.Med 2003;348:1342-1347
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)
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
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
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.Carted.Hosp Epdermid
1995;16:18-24
Characteristics of Strains
Hospital acquired MRSA highly resistant to multiple
antibiotics except Vanco, Rifampin, Gentamicin.
Community acquired MRSA sensitive to TMP/SMZ,
Rifampin, Clindamycin, Linezolid, Vancomycin, except
Penicillin and Cephalosporin
and also Quinolones
CA - MRSA Distinguishing Features
•
•
•
•
Absence of Hospital - Associated risk factors
Susceptibility to most antibiotics other than β-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
Comparison of Staphylococcal
Cassette Chromosome mec Types
mec
SCCmec ccr Gene
Complex Size (kb) RE Type
Type
Type
Type
I
1
B
34.3
i
II
2
A
53.0
ii
III
3
A
66.9
iii
IV
2
B
20.9-24.3
ii
ccr, cassette chromosome recombinase; RE, right extremity of SCCmec element
Adapted from J Infect Dis. 2002; 186:1344-1347
MRSA bacteremia is associated with
significantly higher mortality rate than
is MSSA bacteremia.
(adds ratio 1.93; 95% C.I, 1.54 - 2.42; P<.001)
CLIN. INFECT. DIS 2003; 36:53-59
NEW PROBLEMS RAISED
BY CA-MRSA
• Treatment failure with accompanying
complications or death (if β-lactam antibiotic
is used)
• MRSA strains may be more difficult to treat or
more expensive to treat
• Vancomycin is inherently less efficacious
ANN INTERN MED 1991; 115:674-680
CLIN INFECT DIS 2000; 30:368-373
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
Reasons why 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
Clinical Reports of CA-MRSA in the
US and Around the World
Chicago, Illinois, USA
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; 279:593-598
Dallas, Texas, USA
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; 178:593-598
San Francisco, California, USA
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: 425-433
Midwest Cluster, USA
CDC four pediatric deaths from communityacquired 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; 48:707-710
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 2001:20:860-863.
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; 50:277-280.
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 53:792-795
CA - MRSA among competitive sports
participants Colorado, Indiana,
Pennyslvania, L.A. 2000-2003.
5/70 Fencing club members and household
contacts (3 confirmed, 2 probable, 1
household contact).
1 patient - paraspinal myositis with
bacteremia
4 patients - abscesses (3 patients). All same
PFGE.
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.
Outbreaks of CA-MRSA Skin Infection
in Los Angeles, 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)
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; 36:131-139
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; 32:2858-2862
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; 9:486-493
MRSA presenting like spider bite
MRSA (Spider Bite Like)
Diagnostic Sensitivity
• Agar and broth dilution: 98 - 100%
• Disk diffusion
: 61 - 96.4%
(molecular gene detection for mec A gene or
PBP 2a - usually not available
commercially)
D TEST
The circular area around Clindamycin with a flat
or blunted edge adjacent to erythromycin is proof
of inducible resistance to Clindamycin.
CLINICAL PRESENTATIONS
Currently, most infections caused by CA-MRSA are
skin infections
(eg., abscesses, cellulitis, impetigo, furuncles).
Other types of infection: Otitis, Pneumonia, Bursitis,
Osteomyclitis, Septic arthritis and Blood stream
infections.
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; 19:1123-1128
To date, no standard of care exists for the
management of CA-MRSA and treatment
guidelines have yet to be developed.
Robert C. Mollering Jr. MD, 2003
Susceptibility of CA-MRSA isolates identified
at selected Minnesota hospitals, 1996 - 1998
Antibiotic
Ciprofloxacin
Clindamycin
Erythromycin
Gentamicin
Oxacillin
Rifampin
Tetracycline
TMP-SMZ
Vancomycin
Susceptible
(%)
93
93
64
97
0
99
95
97
100
% Intermediately
Susceptible
(%)
3
1
9
1
0
1
0.4
0
0
Resistant
(%)
3
6
27
2
100
0
5
3
0
CLIN. INFECT DIS 2001; 33:990-996
• 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; 79:497-508
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
Treatment
2001 in Minnesota 354 patients with
CA-MRSA 83% were treated
initially with Beta-Lactam
antibiotics
CLIN. INFECT. DIS 2001: 33:990-996
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; 7:178-182
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
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 inhospital
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
SUGGESTION IN MANAGEMENT
OF CA-MRSA
• 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
RX
RESERVE DRUG(s) FOR CA-MRSA
• VANCOMYCIN - in patient [only IV form]
• LINEZOLID, Oxazolidinones
new antibiotic class [IV and PO]
also effective against VRE and also MRSA
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; 47:196-203
CA-MRSA MEASURES TO
PREVENT SPREADING
• Instruct patient in hand washing
• Sharing of personal items (e.g. athletic
equipment, towels) should be avoided
• Compliance with antibiotic treatment
course
Patient, Physician, and Managed Care
Antibiotic Abuse
Patients: do not understand the difference between viral and
bacterial infection and antibiotics are ineffective against
viruses.
Physicians: frequently comply to satisfy patient’s demand
on antibiotics and to maintain their patient base.
Managed Healthcare: increase antibiotic use by discouraging
diagnostic testing and limiting patient assessment time.
“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
MRSA
Additional information from CDC:
www.cdc.gov/neidod/hip/aresist/mrsa.htm
(800-893-0485)
CDC expert strategies and management of CAMRSA. Priorities for future.
[email protected]
Thank You For
Your Attention