Transcript S. aureus - Calgary Emergency Medicine

New Issues in bacteria we thought
we knew so well.
Meet the new Staphylococcus aureus
Donna Holton,
Infectious Diseases, CHR
Oct 23, 2008
HARBOUR BRETON NEWFOUNDLAND
Who am I
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ID specialist with training in epidemiology
GP who worked in outport NFLD 1981-1983
Worked in Kenya doing HIV in the late ’80s
Worked for Health Canada as epidemiologist
(created the TB Guidelines for Canadian
Hospitals)
Self employed epidemiologist (organized the
1997 Canadian Antimicrobial Resistance
Conference)
Worked in Regina as Infectious Diseases doctor
Work in Calgary as ID and do HIV and Infection
Control
Who am I
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I have done talks for all the companies re:
antibiotics and HIV
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Abbott, BMS, Wyeth-Ayerst, GSK
Interested in biofilm infections and hospital
building design
HIV trials with a wide variety of companies
Tibotec, GSK, Abbott, Boehringer-Ingelheim,
NeurogesX, Argos Therapeutics, Gilead, Pzifer,
Merck
I sit on three boards for new HIV drugs
(Abbott, Kaletra: Merck, Raltegrevir: Pzifer,
Maraviroc)
I am part of the committee writing Canadian HIV
treatment guidelines
Learning Objectives
Methicillin resistant Staphylococcus aureus
MRSA
1.
2.
3.
4.
5.
How have Staphylococcus aureus infections
changed?
What is the prevalence of MRSA in the CHR
Infection vs colonization
Treatment- who, what , and when?
What will the future look like?
With Many Thanks
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To all the IPCs who collect the
bloodstream infections and to Stephanie
who enters the data
To CLS and Provincial Lab especially Drs.
Dan Gregson, Deirdre Church and Marie
Louie
To all IPCs who took part in the Mark of
Zoro study
Staphylococcus aureus
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Very successful bacteria:
can infect anyone bacteria
Ubiquitous
In the days before
antibiotics whole wings of
hospitals were filled with
people who had chronic S.
aureus infections
2% of lactating women died
of S. aureus mastitis
S. aureus causes
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Soft tissue infections
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Basically any, impetigo, cellulitis, muscle abscess
Joint infections
Surgery site infections
Endocarditis
Osteomyelitis
Prosthetic device infections
Others: pneumonia, organ abscesses
Produces toxins that cause different diseases
 food poisoning, toxic shock
My Jan 28th case
Why is my patient not improving?
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40 yr female with abscess in her left thigh
WBC 22 with 20 neutrophils
Blood cultures negative
Not toxic, just not getting better
Clinical issues
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the usual bacterial suspects that cause
uncomplicated soft tissue infection are
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Group A Streptococcus
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S. aureus
Cultures rarely done
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Because this lady has a large abscess, the
pathogen is more likely to be S. aureus
rather than Group A Streptococcus
Staphylococcus aureus is a
common cause of infection
Name five drugs from five different
antibiotics classes that are
a) Oral S. aureus antibiotics
b) IV S. aureus antibiotics
15 Classes of anti-S. aureus drugs
Class
Penicillin
Cephalosporin
Carbapenum
Sulfa
Macrolides
Lincomycins
Tetracyclines
Glycopeptide
Quinolones
Others
Oral (n=9 )
IV (n=12)
Cloxacillin
Keflex
Cloxacillin
Ancef
“septra”
All
Meropenum
“septra”
Azithromycin
Clindamycin
All
Not cipro*
Linezolid
Fusidic Acid
Rifampin
Clindamycin
Vancomycin
Levo, Moxi
Linezolid,
Tigecycline,
Daptomycin,
Synercid
*CIPRO
has an
MIC that
just works
but that
also
means it
often fails
against S.
aureus.
Spain has
a > 30%
resistance
rate
**Rifamycins
work but not
alone
My Jan 28th case
Why is my patient not improving?
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40 yr female with abscess in her left thigh
WBC 22 with 20 neutrophils
Blood cultures negative
Nasal and rectal cultures negative for
MRSA
Superficial wound (skin intact) swab grew
Cloxacillin susceptible S. aureus
In your practice, what kind
of soft tissues infections
are you seeing?
If you are aware of several patients
have MRSA, do they have the same
spectrum of disease?
In HPTP we are seeing a new
spectrum of disease
90% are variations of soft tissue themes
 Story of the Spider bite
 Large often complex abscesses
 Multiple skin lesions
 Co-infection with Group A Streptococcus
 Patients have multiple infections despite
good treatment
 Patients come from the community
Carbuncle
Furuncle (boil)
Abscess
Folliculitis
Courtesy Melissa Tobin-D’Angelo, Georgia DHR
We are seeing a new spectrum of
disease
~10% infections creating critical illnesses
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Necrotizing pneumonia
-Vayalumkal (new ped ID staff) article CJEM
2007:9(4):300-3.. Pt died
-CDC is investigating 2 deaths (11 yr old and
13 year children) who died when MRSA
complicated a viral “flu” like illness (2008)
22/73 kids who died of influenza in 2006-7
had Staphylococcus 2nd bacterial infection
 Rare cases where it caused necrotizing
fasciitis, purpura fulmanans
This type of MRSA seems to have acquired new
abilities to cause critically serious disease
Courtesy of M. Farley
BMJ 2006;332;838-841
My Jan 28th case
Why is my patient not improving?
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40 yr female with abscess in her left thigh
WBC 22 with 20 neutrophils
Blood cultures negative
Nasal and rectal cultures negative for MRSA
Superficial wound swab grew Cloxacillin
susceptible S. aureus
Smart hospitalists are concerned this patient has
an antibiotic resistant S. aureus
Hospitalist was concerned patient
had Methicillin resistant
Staphylococcus aureus (MRSA)
Which of the 15 class(es) of
Staphylococcal Drugs can not be
used if a patient has MRSA?
MRSA has developed resistance
to ALL current Beta Lactams
Name the three beta lactam
classes
MRSA = resistance to all of current
beta lactam antibiotics
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All of the penicillin class regardless of
generation or complexity i.e., can not use
Cloxacillin, Clavulin or Tazocin
All of the current cephalosporins
regardless of generation
All of the current carbapenum
(meropenum, imipenum, ertapenum)
And MRSA usually comes with even MORE resistance than this!!!
12 non-Beta lactam S. aureus drugs
Class
Oral (n=9 )
IV (n=12)
Penicillin
Cephalosporin
Cloxacillin
Keflex
Cloxacillin
Ancef
“septra”
All
Clindamycin
Meropenum
“septra”
Azithromycin
Clindamycin
Carbapenum
Sulfa
Macrolides
Lincomycins
Tetracyclines
Glycopeptide
Quinolones
All
Others
Linezolid
Fusidic Acid
Rifampin
Not cipro*
Vancomycin
Levo, Moxi
Linezolid,
Tigecycline,
Daptomycin,
Synercid
*CIPRO
has an
MIC that
just works
but that
also
means it
often fails
against S.
aureus.
Spain has
a > 30%
resistance
rate
**Rifamycins
work but not
alone
Why is this resistance so
important that the Alberta
Government has declared
war on it?
Because the loss of the
Betalactam = the loss of
bactercidal antibiotics
If the Betalactms are gone so are
the Fluroquinolones
What is an Antibiotic Resistant
Organism?
An organism that
We can no longer use our first
string (bactercidal) antibiotics
We still have antibiotics but we are
sending in the second string
(bacteriostatic)
12 non-Beta lactam S. aureus drugs
Class
Oral (n=9 )
IV (n=12)
Penicillin
Cephalosporin
Cloxacillin
Keflex
Cloxacillin
Ancef
“septra”
All
Clindamycin
Meropenum
“septra”
Azithromycin
Clindamycin
Carbapenum
Sulfa
Macrolides
Lincomycins
Tetracyclines
Glycopeptide
Quinolones
All
Others
Linezolid
Fusidic Acid
Rifampin
Not cipro*
Vancomycin
Levo, Moxi
Linezolid,
Tigecycline,
Daptomycin,
Synercid
**Rifamycins
work but not
alone
Betalactam antibiotics work by
interfering with the penicillin
binding proteins (PBP).
This prevents the bacteria cell
wall from being built
Think Cement Retaining Wall
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S. aureus builds cross links in the bacteria
cell wall that strengthen the wall (think
rebar)
 If beta lactams can bind to the cell wall,
the beta lactams prevent the cross links
 The cell wall has no “ribar” and collapses
 The bacteria die
MRSA means that S. aureus has worked out
how to prevent Beta lactams from binding
Mechanism of Staphylococcus
aureus Methicillin Resistance
Beta lactam antibiotics bind to penicillin binding
protein 2 (PBP 2)
 When S. aureus changes PBP 2 to PBP 2’ (also
called PBP 2a) all currently licensed for use in
Alberta beta lactam antibiotics become useless.
-Change occurs via the Mec A gene.
In the presence of the Mec A gene, the beta lactam
antibiotics can not attach to the PBP and so the
bacteria grow because the bacteria cells walls are
cross linked and strong
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A short history of S. aureus
Resistance
Penicillin (the drug not the class)
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1928 - Penicillin discovered
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1939 - Penicillin first used as treatment
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1945 - Resistance to penicillin identified
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1980’s < 1% susceptible to penicillin
A short history of S. aureus Resistance:
Solving Penicillin Resistance
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1959 Vancomycin created and looked like drug
of choice
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1959 Methicillin introduced
followed by many “copycat” semi synthetic
penicillins (i.e., cloxacillin, oxacillin, nafcillin)
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1964 first cephalosporins introduced (Ancef)
A Short History of S. aureus resistance:
Develops Resistance to Semi-synthetic
penicillins and cephalosporins
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1961 - First identified MRSA (UK)
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1981 - MRSA appears in Canada
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1995 - MRSA begins to escalate in Canada
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1999 – 6% of S. aureus are MRSA in Canada
Antimicrobial Resistance among Nosocomial
Infections with Gram-Positive Pathogens, Canada
(yellow) & US (green) and by ICU Status (pink)
United States
Canada
Source: NNIS Data:Fridkin and Gaynes
Clinics in Chest Medicine June ‘99 303-16
CNISP 2000 (colonization/infection)
Figure 1. Incidence and rate per 1,000 patient
admissions for MRSA (infections and colonizations) from
1995 to 2006 in Canadian hospitals participating in CNISP
Rate is blue line
# of cases = red bars
Data from CNISP Jan 2008
To all organisms
Resistance is not futile,
Resistance is survival
S. aureus has 4 different
alphabet soup names to
describe resistance
MRSA, hVISA,
GISA (not VISA), VRSA
Look up Staphylococcus aureus
in Infection Control manual
S. Aureus resistance to
“methicillin” and Vancomycin
1 use methicillin 1959
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 1 MRSA 1961
Methicillin
 1 MRSA US
Outbreak
Vancomycin
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Vancomycin
st
st
st
30
20
10
Europe, UK
Aus, India
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% Resistance
40
USA ,Aus
Ireland
intermediate resistance
1997
Vancomycin
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Worldwide
0
1940 1950 1960 1970 1975 1980 1985 1990 1995 2000 2003
Year
Resistance2002
What is happening to
S. aureus Calgary?
Number
MRSA isolates (in and out patients) ACH
65
60
55
50
45
40
35
30
25
20
15
10
5
0
59
38
24
1
1
5
5
3
4
5
4
6
8
11
1986 1992 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
Years
S. aureus Bacteremias
160
Odd year
Number of cases
140
120
100
MSSA
80
MRSA
60
40
20
0
10.6
2003
13.4
16.7
23.9
2004
2005
2006
34.3 %MRSA
2007
Year
Calgary Health Region,
Adult Nosocomial Blood Stream Infections
40
35
Per cent
30
25
SA
20
15
10
Total BSI
5
0
2002
2003
2004
%BSI that are MRSA
Fiscal Year
2005
2006
2007*
%S. aureus that are MRSA
Stable rate of BSI per 1000 patient days (0.8)
Comparison of Organisms Having Multiple Drug Resistances 2004 to 2007 (Fiscal Year)
Organisms Having Multiple Resistances
Organisms Having Mulitple Drug Resistances
2004 fiscal
year (n=41)
2005 fiscal
year (n=43)
Pseudomonas
Pseudomonas
MRSA
Klebsiella
VRE
Escherichia
VRE
Klebsiella
oth Gram Negative
MRSA
Escherichia
Klebsiella
Pseudomonas
Escherichia
Klebsiella
Escherichia
oth Gram
Negative
VRE
5%
E. coli
Enterobacter
4%
2007 fiscal
year (n=82)
4%
2%
VRE
7%
Pseudomonas
VRE
Organisms Having Multiple Drug
Reisistances 2007
Organisms Having Multiple Drug
Resistances 2006
2006 fiscal
MRSA
year (n=56)
7%
MRSA
MRSA
5%
MRSA
1%
VRE
E. coli
13%
Enterobacter
Klebsiella
Klebsiella
5%
58%
14%
Pseudo
59%
15%
1%
Other Gram
Negative
Steno
Other Gram Negative
Steno
0%
Pseudo
% MRSA in ER isolates
S. aureus in CHR Emergency Room: prior to
2004 slow but steady increase in per cent
6
MRSA
5
4
3
2
1
0
1985
1990
1995
Year
2000
2005
% MRSA in ER
isolates
From 2004 to Dec 2007,
MRSA took off
30
25
20
15
10
5
0
1985
1990
1995
Year
2000
2005
2007
MRSA seems to have changed
Before 2004, MRSA was acquired in
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Acute Care Hospitals
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Long term care
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75% of cases
Specific clones
10% of cases
Community
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8%
As a resident at FMC I meet my
first “Hospital MRSA”
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This MRSA was the one in the journals
Was associated with Thames, Australia, U.S. Burn
Units
Only available antibiotic was Vancomycin
Occurred in
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elderly, frail hospital patients
burn, ICU and dialysis units
Caused infection (bacteremias) but a lot of people
just seemed to be colonized
This organism plus VRE were the basis of creating
increased isolation in acute care settings
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Private room
Standard + contact
After that first patient my MRSA
experience changed
“Prairie” MRSA
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caused simple skin infections
had an effective oral agents (TMP-SMX,
clindamycin)
occurred in an isolated population (First Nations)
was found on the Prairies
Was not a research project, no one was able to get
any traction for research on this type of MRSA
So we treated the kids and young people with Septra
and they got better.
2005
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Until 2005, the majority of MRSA isolates
came from the hospital environment
Since mid 2005, most of the MRSA isolates
came from the community
Clinical Syndromes – Invasive MRSA
EIP Active Bacterial Core(ABCs) MRSA
Surveillance2004 – 2005
New%
Old%
(n=865) (n=5522)
Skin / soft tissue infection
Pneumonia
Endocarditis (? New biofilm gene(s))
Internal / deep seated abscess
33.8†
16.3
11.5†
9.0†
10.2
14.1
5.0
4.4
Osteomyelitis
Septic arthritis, native joint
Septic shock
8.3
5.1†
4.3
7.5
2.3
4.4
Endocarditis and / or metastatic
complications (? New biofilm gene(s))
21.3†
9.9
Bacteremia
Bacteremia, uncomplicated (no source)^
80.5†
23.8†
88.2
47.4
†Difference tested by Chi Square with p value <0.0001
Ray SM et al. IDSA 2005
Type of MRSA causing bacteremia
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Prior to 2006, most of the nosocomial
bacteremias were caused by MRSA 2, 6,
and 8 i.e, the “hospital” or “old” MRSAs
Since 2006, the “new” or Community or
“10” MRSA is the major cause of the MRSA
bacteremias
My previous antibiotic
suspectibility patterns persisted
GISA
Boyce JM (2003), Clin Updates ID
Since 2004 epidemiological
questions became important.
What are the five current CHR
risk factors for MRSA?
I tell the clerks and residents in
HPTP if they can not answer this
question for each patient with soft
tissue infections I will fail them
MRSA Risk Factor Questions
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“Old question” Do you a lot of contact with the
hospital system
Do you volunteer, work or live at
the jail
the drop in center
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Do you smoke, inject, snort any recreational
drugs?
Are you or anyone you know MRSA positive?
secondary questions “do you work on the rigs, in construction,
do you work out at a gym”
Who are the MRSA patients now?
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Hospital (Old)
Elderly or renal patients
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Community (New)
Young people, jail, drugs,
homeless
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Many visits to hospital
Lots of positive nasal
swabs
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Few visits to hospital
<50% of nasal swabs
positive
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Not a lot of infection
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Lots of infection
Called “hospital”
acquired MRSA
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Called “community”
acquired MRSA
Risk Factors for Neonatal MRSA
Infection in a Well-infant Nursery
Nguyen 2007 ACHE 28(4): 407-411
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Risk for newborn infants to have MRSA
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Circumcision
2nd outbreak had multi-dose lidocaine vial
Surgical instruments uncovered
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Infections often looked like diaper rashes
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Investigation of moms. No MRSA in nose
The lab has now worked some
of my previous epi questions
The Staphylococcal resistance is much
more than “just” a MEC A gene
Methicillin Resistance in
Staphylococcus aureus
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

beta lactam antibiotics work by interfering with
the penicillin binding proteins (PBP)
MRSA organism change the PBP2 i.e., PBP2
becomes PBP2’
Resistance comes on a cassette called
staphylococcal chromosomal cassette Mec
(SCCmec). Cassette has
 Mec A
 Two regulatory genes (Mec I and Mec R1)
 Two site specific recombinases
 +/- other antibiotic resistances
The size of the cassette (SCC)
suggests if resistance to other
antibiotics might be present
Larger cassettes have more room to
carry more than “just” beta lactam
antibiotic resistance
bp
MW
SCCmec I
(613)
II
(398)
III
IVa
IVb IVc IVd V
(280)
(776)
(493)
(200) (880) (325)
MW
CLS M-PCR typing scheme for SCCmec
100
080
0
60
050
0
40
0
30
0
20
0
10
0
mecA
Current SCCmec types and Type IV
subtypes
SCCmec
GenBank
types and
subtypesa
mec-
ccr-
Where
found
I
Class B mec Type 1 ccr
Hospital
No. and
Reference
AB033763 (1)
II
Class A mec Type 2 ccr
N315
D86934 (1)
III
Class A mec Type 3 ccr
Hospital
AB37671 (1)
IVa
Class B mec Type 2 ccr
Community
AB063172 (3)
IVb
Class B mec Type 2 ccr
Community
AB063173 (3)
IVc
Class B mec Type 2 ccr
Community
AB096217 (4)
IVd
Class B mec Type 2 ccr
Community
AB097677
V
Class C mec Type 5 ccr
complexb
complexc
AB12121 (5)
SCCmec
types:
mec
complex
B, C, D)
ccr complex
(A, (1, 2, 3 & 5: ccrA1-4, ccrB1-4 &
ccrC)
J
(Junkyard)
Type IVc
Type IVd
Type V
type 5 ccr
(ccrC)
ccrC: single copy of
a new gene encoded
cassette
chromosome
recombinase
Modified from Okuma et al J Clin Micro 2
Other MRSA naming schemes
Simple
Hospital
Acquired
Community
acquired*
Canada
NML
2, 6, 8
United States
10, 7
300, 400
100, 200
*Very complex wording ..
Hospital associated community acquired MRSA
National Lab
has now
changed to
spa
Why is CA-MRSA 10 different?
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


No one is sure
Some ideas have been put forward
 PVL (presence increases from 1.6% to 18%)
 agr gene changes
 Enterotoxin H and 15 superantigens
 Combinations of changes
But from your practice point of view, it is
different..
The U.S have very rapidly moved to 59%
(Morgan 2006 NEJM) S. aureus infections are
MRSA and the “risk” groups are not holding
My patient uses crack cocaine daily
and
her partner is MRSA positive
and
She says she had an MRSA buttock
abscess last year in Edmonton
My Jan 28th case
Why is my patient not improving

Smart hospitalists: Start Cloxacillin, Vancomycin

Why is she not getting better?
U/S show 15 cm!!!! Abscess. Culture grows MRSA.
No source control. No control of infection
We will need to get smarter about
treating abscess to avoid hVISA, GISA

1.
2.
Paper after paper is saying how important it
is to drain the abscesses.. This takes time
What PPE should we use? Should you wear a
procedure mask to open an abscess
How do we clean the room?
Background




MRSA infections can cause worse clinical
outcomes than MSSA infections
CNISP reported increased rate of MRSA
in Canadian hospitals from 0.46 to 5.90
per 1000 admissions 1995-2004
Health care costs of MRSA in Canada
estimated at $82 million in 2004
Patients with MRSA require prolonged
hospitalization (average 26 days)
Goetghebeur M, Landry PA, Han D, Vicente C. (2007). Methicillinresistant Staphylococcus aureus: A public health issue with economic
consequences. Can J Infect Dis Med Microbiol. Vol. 18. No 1.
January/February
Alberta Government Guidelines 2007
MRSA changes face of oseomyelitis
Gever, June 30, 2008


290 kids with osteomylitis
1999-2001 22.6% MRSA
2001-2003 31.1% MRSA
33/290 kids had MRSA osteomyelitis


69% of MRSA had bone abscesses vs 11-39%
of other cause (p < 0.05)
Significantly longer median days with fever,
complications, days to normal CRP and Sed
rate, days of hospitalization
In the Adult World


Some paper have shown that so long as
you anticipate MRSA, that outcomes are
similar. My concern is that the patient
description makes me think MRSA 2, 6, 8
i.e, the “old” MRSA
Will come back to this in the future section
Strain specific rates (per 100,000), by
Month for MRSA in Alberta
8.00
(Jan 1, 2006 -Dec 31, 2007)
7.00
6.00
Rate (per 100,000)
5.00
4.00
3.00
2.00
1.00
0.00
Jan-07 Feb-07 Mar-07 Apr-07 May-07 Jun-07
CMRSA 2 (n=855)
CMRSA 6 (n=158)
Jul-07 Aug-07 Sep-07 Oct-07 Nov-07 Dec-07
CMRSA 7 (n=218)
CMRSA 8 (n=31)
Alberta Government Guidelines
CMRSA 10 (n=2,089)
Strain specific rates (per 100,000), by Health
Region for MRSA in Alberta (Jan 1, 2006 -Dec 31, 2007)
CMRSA Strain Type
Health Region
2
4
6
7
8
10
Chinook
53.0
0.0
0.3
14.4
0.6
25.2
Palliser
45.4
0.0
0.0
1.5
0.5
34.7
Calgary
32.0
0.1
0.4
5.8
1.5
59.9
DTHR
62.8
0.3
3.3
3.3
0.3
30.0
East Central
12.1
0.4
5.8
4.5
0.4
15.7
Capital
7.1
0.0
9.4
4.6
0.3
45.5
Aspen
7.0
0.6
8.5
9.0
1.1
32.1
Peace Country
5.4
0.0
2.9
1.8
0.0
59.0
Northern Lights
3.3
0.7
2.0
11.3
1.3
92.0
ALBERTA
24.7
0.1
4.2
5.5
0.8
48.0
Alberta Government Guidelines
MRSA has attracted a lot of
government interest




Poster bug for adequacy of infection
control
Demonstration project to show
effectiveness of government oversight of
health care
Much responsibility has been passed along
Limited resources provided
A Balancing Act

Try to limit risk to others re transmission


Admitted to take part in a program





Some would have us lock MRSA positive
patients in their rooms
Day care, schools
Rehabilitation
Psych
Elderly programs
Acute Care, Long Term Care schools have
different goals for clients
AHW states
Primary mechanism for
transmission of MRSA is via HCWs
who are temporarily colonized
with MRSA
But infection control
rarely has a single action
that effectively stops an
event
Framework for Intervention
Infectious agent
What is the ability
of the host to stop
invasion
Portal of entry
Reservoirs
Chain of
Transmission
Portal of exit
Means of transmission
AHW acknowledges these risk
factors for Community MRSA:
the 5 C’s





Cleanliness
Crowding
Contact
Sharing Contaminated articles
Compromised skin
These are “community risk factors”.
What do they look like as health care risk
factors?
AHW acknowledges these risk factors
for Community MRSA: the 5 C’s

Cleanliness


Crowding



The “old” MRSA was polite with few family members ill.
The “new” MRSA also affects family members.
Sharing Contaminated articles


Over capacity is hard
We need 116-170 isolation beds per day in CHR
Contact


Can not conduct study because asks pts to be bathed
every day
Staphylococcus is a ubiquitous organism. Toys,
computers, hand rails, pagers, cell phones etc etc
Compromised skin
APEC 2006 study



One day prevalence study
In 1237 sites or 21% of US healthcare
facilities
Looking for all patients know to have MRSA
i.e., patient could be colonized or have an
active infection
APEC study results




Rate 16-48 (avg 34) MRSA positive/ 1000 patients
or 1.6 to 4.8% of patients
(11 x higher than expected) (10-17% of colonized)
Gender 54% male, 46% female
Identified by
81% detected by clinical culture
19% by surveillance culture
Site


37% skin and soft tissue
63% other
CHR Prevalence study
Or did we have all the MRSA
patients correctly isolated?



IPC did a quick study looking at 3 adult
units. One unit per site
RGH medicine, FMC orthopedics, PLC
palliative and “overflow” medicine
Did Nasal and “Mark of Zoro” on
admission and at specified intervals
MRSA is already common in
U.S.
MRSA is already here
PLC had the most positives by a
long shot



? Exposure in hospital, health care
We realized that PLC was different in that
we had 2 individual (Jan and Leah) doing
the swabs on the prevalence days and
they did GROIN “z” swabs (my fault, I said
groin) while FMC and RGH ended “z” at
belt level.
? If difference is difference in real life v.s.
technique
ACH
ER Study


Aug-Dec 2007
All children presenting to ER with cellulitis
or abscess

9/50 (18%) shown to be MRSA positive
If you culture MRSA
someone’s skin do they have
an infection?
We all have bacteria on our skin

Some bacteria stay on our skin for long time
periods




Persistent 20% (range 12-30%)
Intermittent 30% (range 16-70%)
Non-carrier 50% (range 16-69%)
Some bacteria may be only transiently present
and if we do proper hand hygiene (alcohol hand
rubs or soap and water) these organisms will
not become part of the “normal” organisms on
skin
-the bacteria are “bounced” off the skin like a
rubber ball off a surface
Finding bacteria
does not
necessarily mean
there is an infection
Local
infection
Systemic
infection
Colonization
Only
temporarily
on skin
“normal”
flora, not
invading
Local redness,
pain, swelling,
heat, pus
Systemically ill
with fever, chills,
rigors
sometimes ICU
serious
Definitions of infection
Invasion and multiplication of micro-organisms in
body tissues associated with tissue destruction
or host inflammatory response
Criteria
1.
Two local findings (redness, warmth, purulent
secretions, pain, tenderness) or
2.
Superficial soft tissue infection must have
cellulitis (redness of the surrounding skin) or
3.
Deep infection.. Presence of abscess, septic
arthritis, osteomyelitis, septic tenosynovitis or
4.
Systemic symptoms
If transient bacteria
become resident bacteria
Deciding what the
bacteria on our skin
are doing
May colonize
i.e., present but
not invading
May cause an infection
Mom’s criteria
105 organism/ gm
of tissue
redness, warmth,
purulent secretions,
pain, tenderness
> 1 ml of pus
If you order a swab
Why are you ordering it
Remember chronic
ulcers will chronically
grow bacteria
GO BACK 1 SLIDE if do
not know if colonization
or infection
To see if Colonized
i.e., present but
not invading
To identify the
cause of an infection
MRSA surveillance
swab
Order Wound swab
Report will say
Yes MRSA present or
No MRSA found
Report will tell what
Antibiotics you can use
Lab report says
MRSA positive
What does that mean?
Patient needs to be placed
under contact precautions
Why was the swab taken?
Clinically what does the pt look like
No obvious infection
Patient colonized
You do not need
To order any further
MRSA screening swabs
IPC will order
Mom says infected
Use results to help guide
therapy for an infected wound
Use information
to treat infection
(infectious disease
What does Treatment look like for
MRSA 10?

Septra





Population has 8% rash rate
Causes problems with breast feeding moms
Premies do not do well
Issues with G-6PD deficiency
Clindamycin:


Not good if local C. difficile happens to be F
strain (very high association with Clindamycin
Tastes terrible as liquid

What does Treatment look like for
MRSA 10?
Tetracyclines


Vancomycin


Are not given to young children
IV medication
Linezolid



PO or IV
Currently must fail Vancomycin to get
Issues re hemogloblin
In the Adult HPTP World

Ancef


Ancef + Septra (Tetracycline, clindamycin)


Ancef + clindamycin works well with the “aggressive MSSA
+ Group A strep” cellulitis + Group A
Ancef + Vancomycin



Some people fail on Day 3 ??? Had mixed MSSA and MRSA
infection. Ancef kills MSSA but leaves MRSA untouched
Cellulitis in face
ICU patient with Staph in blood
Vancomycin

Pt known to have MRSA
Colonization has been associated with
subsequently developing infection




Reported rates have varied
Low 15% High > 30%
Nosocomial bacteremia rate RR 30 (NEJM 2001, von Eiff)
SSI 2-9 fold increase risk of infection (but decolonization
pre-op mupirocin did not decrease risk)
Renal patients (meta-analysis)
 Decrease by 78% risk of BSI in hemodialysis
patients
 Decrease by 66% risk of BSI in peritonneal dialysis
patients

Tacconelli 2003 Clin Infect Dis
Should we decolonize patients
because colonized patients have
a high risk of developing an
active infection
What is Decolonization?



Use of topical and/or systemic agents to
eradicate/reduce MRSA carriage on skin and
mucus membranes
Purpose is to reduce risk of transmission in
healthcare settings
Efficacy dependent on multiple factors related to
the patient e.g. health status, wounds, foreign
bodies, feeding tubes, compliance
To Decolonize or Not
Yes
Associated with 1530% chance risk of
infection
 May prevent re-current
infections
 Good for public health
because decrease
transmission
No


Cochrane review 2003 did





not support use of
decolonization
Not recommended by
AMMI, PHAC, CDC
Patients fail
Patients will reacquire
S. aureus will develop
resistance to
chemicals/drugs we use
Will not change genetics
that result in person being
colonized
Who should we try to decolonize


All patients?
Choose subsets of patients




All patients with access lines?
All patients with more than 3 infections in six
months?
All patients who will be compliant
No patient

Cazaban 2007 ICHE looked at outcomes. If
had non-pneumonia MRSA infection in
hospital no worse outcome than MSSA. Just
be smarter when we treat
How Has Decolonization Been
Done

Most reviews do not support intranasal
mupirocin alone UNLESS



short term use for patients about to undergo major
surgery (e.g. cardiac, ortho) OR
conventional methods have failed to control an
outbreak (e.g. NICU)
Multiple agent intervention more successful and
generally used for very selected patient
populations or HCWs (e.g. surgeons).
Generally use combinations of mupirocin, CHG,
and if susceptible combos of clindamycin or SXT
or rifampin
How Has Decolonization Been
Done


Most groups have used nasal mupirocin +
2% CHG body washes
Some groups have used


PO Vancomycin to resolve GI carriage
Some have treated positive urine



2nd commonest first clinical isolate in CHR is urine
(Dan Gregson)
Some have treated positive vaginal culture
Some have treated positive throat cultures
Andy Simor’s Study
Clin Infect Dis 2007





2% CHG wash
2% intranasal mupirocin
Rifampin x 7 days
Doxycycline x 7 days
(can TB land tolerate this medical use of
their VERY IMPORTANT drug)
Andy’s results

Significant eradication at 3 months


75% with program, 32% without
At 8 months

54% still negative (so 21% returned to be
positive)
My roadside conversations with
Tom Louie

Yes you can decolonize MRSA 2


Interesting because are the folks with the
“holes” (stasis ulcer, PEGs etc)
Very hard to decolonize MRSA 10

2% CHG in nares works better than mupirocin
The “core” patients are not in
easy to do locations



Can you do this in the high risk areas of
jails, drop in centers, ER, Urgent Care
Can you do this in high risk clinical areas
(HPTP, SAC, STI)
We couldn’t do it the acute care settings
and Tom responded by making an
outpatient clinic
Summary Recommendations
For Decolonization


No group or organization has supported
decolonization for all patients
Some support for selected Decolonization
(if mupirocins)




Dialysis patients
Recurrent infections
Infection control measure
Do Not use routine decolonization in preop or non-surgical patients
Good
Hand
Hygiene as
prevention
remains
good plan
but can we
do it
Resident flora Transient flora
Good Hand Hygiene for everyone
Start of activity,
End of activity
Staff
Patients
Volunteers
Visitors
Are we now where we were in
the early 1980s with HIV?
In the 1980’s we learnt that we could not
tell if someone is HIV positive or not
VIEW ALL BLOOD AND BODY SUBSTANCES
as potentially carrying BLOODBORNE
PATHOGENS



MRSA prevalence rates are growing in the
community
Risk factor are breaking down
No magic way to detect MRSA
Should we assume that
everyone and everything is
MRSA positive?
Here are four actions you can take
to protect your children from MRSA
1. If your child has a booboo, put a
bandage on it. MRSA is usually spread
by skin-to-skin contact. Bandages
protect broken skin from MRSA and
also reduce the risk of spreading
MRSA to family members and friends
if a wound already is infected.
Here are four actions you can take
to protect your children from MRSA
2. Wash your hands with soap and water, and
don't be timid about nagging kids to wash
their hands, too. Boring, but it works.
If you are cleaning a wound
Clean potentially contaminated surfaces
with ¼ cup bleach(5.25%) to 4 gallons of
water)
Wear gloves when cleaning a wound but
REMEMBER you MUST ALSO WASH your
hands.
Here are four actions you can take
to protect your children from MRSA
3. Discourage sharing of towels, razors,
and other hygiene items, which are
often implicated in MRSA outbreaks.
That's one reason MRSA outbreaks
have been more common in school
athletic teams. This could be the best
way ever to scare boys off towelsnapping! Also, tell kids not to share
clothes or other personal items.
Here are four actions you can take
to protect your children from MRSA
4. Call the doctor ASAP if a family
member has a skin infection and also
a fever. Most staph infections look like
a bump or infected area that is red,
swollen, painful, and warm to the
touch. Rapid treatment with the right
antibiotics makes it easier to get rid of
the bug.
Will MRSA always be an
Antibiotic Resistant Organism?
12 Classes of anti-S. aureus drugs
Class
Penicillin
Cephalosporin
Oral (n=9 )
Cloxacillin
Keflex
Carbapenum
IV (n=12)
Cloxacillin
Ancef
Meropenum
Sulfa
Macrolides
“septra”
All
“septra”
Azithromycin
Lincomycins
Tetracyclines
Clindamycin
All
Clindamycin
Glycopeptide
Quinolones
Others
Not cipro*
Linezolid
Fusidic Acid
Rifampin
Vancomycin
Levo, Moxi
Linezolid,
Tigecycline,
Daptomycin,
*CIPRO
has an
MIC that
just works
but that
also
means it
often fails
against S.
aureus.
Spain has
a > 30%
resistance
rate
**Rifamycins
work but not
alone
New Anti Staph Agents
Antimicrobial
Agent
Class
Route of
Administration
Ceftobiprole
Cephalosporin
IV
Ceftaroline
Cephalosporin
IV
Cethromycin
Ketolide
Oral
Dalbavancin
Lipoglycopeptide
IV
Doripenem
Carbapenem
IV
Iclaprim
Diaminopyrimidine
IV
Oritavancin
Glycopeptide
IV
Prulifloxacin
Quinolone
Oral
Telavancin
Lipoglycopeptide
IV
The Future





Infectious diseases is hoping that the new
IV cephalosporins and carbapenem are as good
as we think
The new cephalosporins target the PBP2’ i.e.,
the PBP that Mec A makes
Side effects
-Ceftobiprole (rash, nausea, bad taste)
-Ceftaroline (mild headache)
We hope that at some of the other drugs in
development pan out, a new oral agent would
be wonderful
These are very broad spectrum antibiotics
Question for 2010-2012



At some point in the not distant future we
will have more MRSA than MSSA. MRSA
will become our new “Norm” of S. aureus
We will have at least 3 new antibiotics
from 2 classes that will be bactercidal for
MRSA
Could we “de ARO” MRSA as we did in the
1960’s re penicillin resistant S. aureus?
Could we “de-ARO” MRSA
Pro
 Scientifically, likely yes
 The system does not have enough beds or
staff to deal with private rooms needs
Con
 Would likely die in the media
 Government has a lot at stake
 We should not be transmitting organisms
MRSA Outbreak reporting

Any person who knows or has reason to
suspect the existence of MRSA:




In epidemic form;
Occurring at an unusually high rate; or
That is caused by a nuisance or other threat
to public health,
Shall immediately notify the regional MOH
by the fastest means possible
Alberta Government Guidelines
Summary
Failure to quickly and
appropriately treat serious
infections will result in poor
patient outcomes.
In mid 2007, 35% of ER isolates of
S. aureus were MRSA
18% kids MRSA swab positive 2007
CA-MRSA 10 will likely permanently
alter S. aureus’ disease profile
There will be more
 abscesses and soft tissue infection
 More person to person transmission (gene(s)
from CoNS)
 10% of the infections will be very serious (?new
pathogen markers)
 Repeat infection since MRSA 10 seems to result
in a poor antibody response
 Very high rate of colonization becoming infection
Very different from MRSA 2, 6, 8
I do not believe we have seen
all that MRSA 10 will do


CHR had a really nasty episiotomy MRSA
infection. I think we may see MRSA
looking like Group B Streptococcus and
Listeria in newborns because I think the
Europeans are correct, MRSA 10 is carried
in the vagina
There is an increasing sense that MRSA 10
are sexually transmitted infections
I do not believe we have seen
all that MRSA 10 will do


S. aureus causes secondary bacterial
pneumonias after influenza infections. We
have not yet had a bad influenza year to
go sour with secondary MRSA pneumonia
We have not really seen MRSA prosthetic
joint infections yet. The paper on
osteomyelitis suggests this may be very
true.
CANADIAN PAEDIATRIC
SURVEILLANCE PROGRAM






Please complete the following sections for the case
identified above. Reporting to the CPSP does not
preclude
a responsibility to report cases of MRSA directly to
the province according to each province’s legislation
on notifiable disease reporting. Patient and reporter
information will be kept confidential.
2305 St. Laurent Blvd.
Ottawa, ON K1G 4J8
Tel: 613-526-9397, ext. 239
Fax: 613-526-3332
[email protected] or www.cps.ca/cpsp
http://www.cps.ca/English/surveillance/cp
sp/studies/Questionnaire/MRSA.pdf
Questions?
References
Guidelines for the prevention and management of CAMRSA: a perspective for Canadian health care
practitioners
 Can J Infect Dis Med Microbiol 2006 (supplC): 4c-24c
Control and treatment of MRSA in Canadian paediatric
health care institutions.
 Paediar Child Health 2006;11:163-165
Ca-MRSA: Implications for the Care of Children
 Paediatrics and Child Heatlh 2007;12(4) 323-324
Consensus Statement for the management of MRSA
infections in Neonatal ICUs Susan Gerber
 ICHE Feb 2006 27(2): 139-145
CDC Sept 8, 2008
launched program to teach parents about MRSA