Transcript Slide 1

Community Associated
Resistant Bacteria:What
Bugs and What Drugs
Work Against Them?
Lilly Immergluck, MD
Associate Professor of Pediatrics
Divisions of General Pediatrics and Pediatric Infectious Diseases
Morehouse School of Medicine
March 1, 2006
Background Information
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings
Emergence of Antimicrobial
Resistance
Susceptible Bacteri
Resistant Bacteria
Resistance Gene Transfer
New Resistant Bacteria
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings
Selection for antimicrobialresistant Strains
Resistant Strains
Rare
Antimicrobial
Exposure
Resistant Strains
Dominant
What “Bugs” are we talking
about…in Pediatrics?
 Community-associated
Methicillin
Resistant Staphylococcus aureus
 Drug Resistant Streptococcus
pneumoniae
Methicillin Resistant
Staphylococcus aureus
Lowy, Frank,Staphylococcus Infections. NEJM. August, 1998
Types of MRSA

BRSA- Borderline
MRSA
 MRSA- related to
mecA gene=ORSA

Hospital associated
MRSA
 Community
associated MRSA
Mechanism of Resistance for
MRSA
Staphylococcal chromosomal
cassette mec IV, type 4
(SCC mec type IV)
Derensinski S. Clin Infect Dis 2005:562-73
Emergence of USA 300 clone
 Result
of insertion of SCCmecA type IV
 Donor staph isolate is MSSA
 Differences from HA-MRSA:



Gene cassette coding for methicillin
resistance
Carriage of plasmids encoding resistance to
antibiotics of other classes
Associated virulence factor
SCCmec types I-V
SCC
mec
type
Size
of
SCC
mec
Other Antibiotic Resistance
elements on SCCmec
Origin of S.
aureus isolates
Presence of
Panton Valentine
leukocidin
I
34
...
Hospital
Infrequent
II
53
PUB110 (aadD)b, Tn554 (ermA)c
Hospital
Infrequent
III
67
PUB110 (aadD)b, PT181 (tetK)d
Hospital
Infrequent
...
Community
Frequent
...
Community
Unknown
IV
V
21–
24
28
Derensinski S. Clin Infect Dis 2005:562-73
Staphylococcus sp.
 “Isolates
of staphylococci that are shown
to carry the mecA gene, or that produce
PBP2a, the gene product, should be
reported as oxacillin resistant”
Epidemiology of MRSA
 First
described in 1961
 Approximately 50% of Staphylococcus
aureus infections in ICU in US due to
MRSA
Risk Factors for Hospital
acquired MRSA in Adults
 Prolonged/recurrent
antibiotic exposure
 Prolonged hospitalization or ICU
 Chronically ill
 Nursing home residence
 Dialysis or Malignancy
HA-MRSA Prevalence
Lowy, Frank,Staphylococcus Infections. NEJM. August, 1998
Definition of Communityassociated MRSA
Salgado, Farr, Calfee Clin Infect Dis, 2003
Epidemiology of Community
acquired MRSA
 Case
Report in Chicago
 Outbreak among high school wrestling
team in Vermont
 Reports have occurred in Chicago,
Minnesota, North Dakota, Dallas,
Winnipeg, Toronta, and in Australia
Headlines to catch our attention…
• Methicillin-Resistant Staphylococcus aureus
Infections Among Competitive Sports
Participants --- Colorado, Indiana,
Pennsylvania, and Los Angeles County,
2000—2003

Four Pediatric Deaths from CommunityAcquired Methicillin-Resistant
Staphylococcus aureus -- Minnesota and
North Dakota, 1997-1999
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Published:
p
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“Study Finds Spread of
Resistant Staph”
By THE ASSOCIATED PRESS
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7, 2005, NY Times
“PRO FOOTBALL; After Medical
Scare, Giants' Center Improves”

November 4, 2004, Thursday
 By LYNN ZINSER (NYT); Sports Desk
 Late Edition - Final, Section D, Page 4,

“At first, Giants center Shaun O'Hara said he
had no idea why his swollen calf was causing so
much alarm among team trainers last week. He
knew nothing about the staph infections that had
struck seven Miami Dolphins last year,
hospitalizing two of them, or of…”
Fatal Pediatric Infections from
CA-MRSA
Case 1
Case 2
Case 3
Case 4
Age
7 years
16 months
13 years
12 months
Syndrome
septic
severe
arthritis,
sepsis
sepsis,
pneumonia/
empyema
necrotizing
pneumonia,
severe
sepsis
necrotizing
pneumonia,
severe
sepsis
Antimicrobial
susceptibility*
t/s, tet, cip,
gent, ery,
clind, vanc
t/s, tet, cip,
gent, ery,
clind, vanc
t/s, cep, cip,
gent, ery,
clind, vanc
t/s, tet, cip,
gent, ery,
clind, vanc
Toxin test+
SEC
positive
SEC positive
SEB
positive
SEB positive
Source: Centers for Disease Control and Prevention, Atlanta ,
October 1999 / HOSPITAL INFECTION CONTROL
Minnesota Surveillance Study,
1997
Naimi,LeDell et al Clin Infect Dis 2001
Summary of Age Distribution of CAMRSA in Minnesota
N=354
Age
Median
1-10 years
<6 years
Race
Native
Americans
Blacks
Other
(Unknown)
16 years (1-78)
38%
23%
40%*
18%
4% (18%)
*excluded Hospital F which predominantly served native Americans
Naimi, TS et al CID 2001: 33
Clinical Presentation
Maybe as simple as this…
courses.washington.edu, accessed from web 2/28/06
Or more severe as this…
www.emedicine.com/ped, accessed Feb 28, 2006
MRSA Pneumonia/Empyema
Clinical Presentation of Children
with CA-MRSA
Herold, Immergluck, et al JAMA 1998
Summary of Risk Factors for
CA-MRSA
Risk factor type 1
Previously healthy
No recent direct or
indirect hospital/care
facility exposure (e.g.
via family member)
Patients with risk
factor for MSSAb
Risk factor type 2
Risk factor type 3
Risk factor type 4
Patient with primary
skin infections (e.g.
furuncles, impetigo,
scalded skin
syndrome)
Ethic minority group
Age: risk decreases
as age increases
Patients with
abscesses or cellulitis
Low socioeconomic
status
Risk factor from one
group
Low overall risk – culture and susceptibilities not required
Risk factors from all
four groups
Risk indicated that culture and susceptibilities not performed
a
Adopted as a working definition; will include H-MRSA with these characteristics.
See case control study in Moreno et al. [25].
b
Eady, Cove, Curr Opin Infect Dis, 2003
What Drugs Can Treat This
Bug?
“D Test” – positive
reaction
Inducible
clindamycin
resistance
(erm-mediated)
15 - 26 mm
…another example
Photos courtesy of J. Jorgensen and K. Fiebelkorn.
“D Test” – negative
reaction
NO induction
(msrA-mediated
erythromycin
resistance)
MRSA—
Erythromycin/Clindamycin Story
Mechanism
Pathway
Erythro
Clinda
Efflux
msrA
R
S
Ribosome
alteration
erm
R
R*
Treatment of CA-MRSA
 Options
are better than hospital acquired-
MRSA
 Almost all are clindamycin susceptible
 Trimethoprim-sulfamethoxazole
 Role of quinolones
HA-MRSA susceptibility pattern
Profile 1





Clindamcin
Erythromycin
Oxacillin
Penicillin
Vancomycin
Profile 2
R
R
R
R
S






Cefazolin
Clindamycin
Erythromycin
Oxacillin
Penicillin
Vancomycin
S
R
R
R
R
S
CA-MRSA often susceptible to:
 Clindamycin
 Rifampin
 Erythromycin
 Tetracyclines
 Fluoroquinolones
 Trimeth-sulfa
 Linezolid
 Vancomycin
Treatment Regimens

Severe infections, multi drug resistant infections





Vancomycin
Daptomycin
Linezolid (pneumonia)
Quinopristin/dalfopristin
Limited infections, less severe



TMP-SMZ
Linezolid
?No treatment
Data in Atlanta Area
 Adult
studies
 Pediatric studies
Risk Factors for CA-MRSA
Colonization in Adults
 HIV

infection
Lower risk if HIV infected and receiving
antibiotics within 3 months before admission
 History
of skin or soft tissue infection
 Hospitalization within preceding year
 Receipt of antibiotics within 3 months
before admission
Hidron, AI, Kourbatova, EV, et al, Clin Infect Dis 2005
Susceptibility of Isolates, by
pulsed-field type
Hidron, AI, Kourbatova, EV, et al, Clin Infect Dis 2005
Preliminary Data for Atlanta
Children
3169 Staphylococcus aureus isolates
from 1/2002-12/2004



656 (21%) CA-MRSA isolates by phenotype
485 (15%) HA-MRSA isolates by phenotype
Based on data collected from Egleston and Scottish Rite Hospitals
MSSA
HA-MRSA
CA-MRSA
00
4*
42
00
4
32
00
4
22
00
4
12
00
3
42
00
3
32
00
3
22
00
3
12
00
2
42
00
2
32
00
2
22
00
2
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
12
Isolates
Proportional S.aureus isolates at
Scottish Rite
MSSA
HA-MRSA
CA-MRSA
00
4*
42
00
4
32
00
4
22
00
4
12
00
3
42
00
3
32
00
3
22
00
3
12
00
2
42
00
2
32
00
2
22
00
2
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
12
Isolates
Proportional S. aureus isolates
at Egleston
Isolates/10,000 ER visits
Incidence of SSTI due to S. aureus
isolates among Scottish Rite ER
Patients,
2002-2004
25
20
15
10
5
0
1
2
3
4
5
CA-MRSA
6
7
HA-MRSA
8
9
MSSA
10
11
Isolates/10,000 ER visits
Incident CA-MRSA Isolates from
SSTI’s at Egleston and Scottish
Rite
ER
Patients
25
20
15
10
5
0
1
2
3
4
5
6
EGL CA-MRSA
7
8
9
SCO CA-MRSA
10
11
Where do we go from here?
 Surveillance
of children who are colonized
with CA-MRSA
 Understand risk factors for colonization
and subsequent infections due to CAMRSA
 Understand household transmission of
CA-MRSA
 Develop strategies for eradication of
colonization